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  • 1.
    Alimohammadi, Mohammad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Scalp necrosis as a late sign of giant-cell arteritis2013In: Case reports in immunology, ISSN 2090-6609, Vol. 2013, article id 231565Article in journal (Refereed)
    Abstract [en]

    Retinal infarction and scalp necrosis are described as unusual but devastating complications of giant-cell arteritis. We report a patient with this rare complication and emphasize the importance of timely diagnosis and treatment of giant-cell arteritis.

  • 2. Chatzidionysiou, Katerina
    et al.
    Turesson, Carl
    Teleman, Annika
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Lindqvist, Elisabet
    Larsson, Per
    Coster, Lars
    Rydberg, Barbro
    van Vollenhoven, Ronald F.
    Heimburger, Mikael
    A Multicenter, Randomized, Controlled, Open-Label Pilot Study of the Feasibility of Discontinuation of Adalimumab in Rheumatoid Arthritis Patients in Stable Clinical Remission2012In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, no S10, p. S336-S336Article in journal (Other academic)
  • 3.
    Chatzidionysiou, Katerina
    et al.
    Karolinska Inst, Unit Clin Therapy Res, Inflammatory Dis ClinTRID, Stockholm, Sweden.
    Turesson, Carl
    Lund Univ, Dept Clin Sci, Rheumatol, Malmo, Sweden.
    Teleman, Annika
    Capio Movement, Reumatol, Halmstad, Sweden.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Lindqvist, Elisabet
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden.
    Larsson, Per
    Karolinska Univ Hosp, Dept Rheumatol, Stockholm, Sweden.
    Cöster, Lars
    Univ Hosp, Dept Rheumatol, Linkoping, Sweden.
    Forslind, Kristina
    Helsingborg Hosp, Rheumatol Sect, Dept Med, Helsingborg, Sweden;Lund Univ, Dept Clin Sci, Rheumatol, Helsingborg, Sweden.
    van Vollenhoven, Ronald
    Karolinska Inst, Unit Clin Therapy Res, Inflammatory Dis ClinTRID, Stockholm, Sweden.
    Heimbürger, Mikael
    AbbVie AB, Stockholm, Sweden.
    A multicentre, randomised, controlled, open-label pilot study on the feasibility of discontinuation of adalimumab in established patients with rheumatoid arthritis in stable clinical remission2016In: RMD Open, E-ISSN 2056-5933, Vol. 2, article id e000133Article in journal (Refereed)
    Abstract [en]

    Objectives: Treatment with tumour necrosis factor (TNF) blockers, once started as therapy for rheumatoid arthritis (RA), is usually continued indefinitely. The aim of this trial was to assess the possibility of discontinuing treatment with adalimumab (ADA) while maintaining remission in patients with RA with established disease in stable remission on combination therapy with ADA and methotrexate (MTX).

    Methods: In a randomised, controlled, open-label pilot study of patients with RA in stable remission treated with ADA+MTX, patients were randomised in a 1:1 ratio to continue with ADA plus MTX (arm AM) or MTX monotherapy (arm M) for 52 weeks. Flare was defined as Disease Activity Score (DAS28) >= 2.6 or a change in DAS28 (Delta DAS28) of >1.2 from baseline at any time. Patients in arm M with a flare restarted ADA. The primary end point was the proportion of patients in remission at week 28.

    Results: 31 patients were enrolled in the study and randomised to arm AM (n=16) or arm M (n=15). At 28 weeks, 15/16 patients (94%) and 5/15 patients (33%) in arms AM and M, respectively, were in remission (p=0.001). During the first 28 weeks, 50% (8/16) in the AM arm and 80% (12/15) in the M arm had a flare (p=0.08). The number of patients in the AM and M arms with >1 Delta DAS28 >1.2 during the first 28 weeks was 1/16 (6%) and 8/15 (53%), respectively (p=0.005).

    Conclusions: In this study, remission was rarely maintained in patients with long-standing disease who discontinued ADA. Discontinuation may be feasible in only a minority of patients with established RA in stable clinical remission.

  • 4.
    Eriksson, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kozyrev, Sergey V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Dahlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Broad Inst Harvard & MIT, Cambridge, MA USA.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A case of systemic lupus erythematosus with C1q deficiency, increased serum interferon-a levels and high serum interferogenic activity2019In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 58, no 5, p. 918-919Article in journal (Other academic)
  • 5.
    Hellbacher, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hjorton, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Backlin, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Malignant lymphoma in granulomatosis with polyangiitis: subtypes, clinical characteristics and prognosis2019In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 11, p. 1655-1659Article in journal (Other academic)
    Abstract [en]

    Several autoimmune and inflammatory conditions, such as rheumatoid arthritis (RA) and primary Sjögrens’s syndrome (pSS), have repeatedly been linked to an increased risk of malignant lymphoma [1,2]. Certain inflammatory conditions are also associated with the development of specific lymphoma subtypes such as mucosa-associated lymphoid tissue (MALT) lymphoma in pSS and diffuse large B-cell lymphoma (DLBCL) in RA. The underlying mechanisms behind this association remain unclear. The highly increased risk of developing MALT lymphoma of the parotid gland in pSS indicates that local inflammatory processes can promote lymphoma development at the site of chronic inflammation [3]. In RA, an association between disease severity and risk of lymphoma has been shown.

    Granulomatosis with polyangiitis (GPA), formerly Wegener’s granulomatosis, is a systemic small vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) and characterized by granulomatous inflammation and necrotizing vasculitis of the airways and kidneys but possibly affecting any organ system. An increased risk of lymphoma in patients with GPA has been reported in several epidemiological studies [4,5]. However, very little is known about risk factors for lymphoma development in this group, possible relation to disease severity, treatment and lymphoma subtypes or the prognosis for the lymphomas. This is the first published study on GPA and lymphoma, giving detailed information on the GPA characteristics and possible risk factors for lymphoma and also lymphoma subtypes treatment and survival.

  • 6.
    Hellbacher, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hjorton, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Malignant Lymphoma In Granulomatosis With Polyangiitis2017In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56Article in journal (Refereed)
  • 7. Hertzell, Katarina Brodin
    et al.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Rombo, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Vene, Sirkka
    Askling, Helena H
    Tick-borne encephalitis (TBE) vaccine to medically immunosuppressed patients with rheumatoid arthritis: A prospective, open-label, multi-centre study2016In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 34, no 5, p. 650-655Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tick-borne Encephalitis (TBE) is endemic in south-eastern Sweden as well as in the Baltic regions, Central Europe and Russia. Ageing and immunosuppressed individuals are more prone to severe disease and neurological complications. We assessed the immunogenicity of TBE-vaccine in rheumatoid arthritis (RA) patients treated with tumor necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX).

    METHODS: TBE vaccine, FSME-Immune(®) or Encepur(®), was administered to non-immune RA patients as well as age and gender matched healthy controls. Individuals <60 years of age were given three doses at month 0, 1, 12. Individuals ≥60 years old were given an additional priming dose at month 3, i.e. a total of four doses. Tick-borne encephalitis neutralizing antibodies were assessed by a rapid fluorescent focus inhibition test.

    RESULTS: The study population consisted of 66 patients and 56 age and gender matched healthy controls. Median age was 58.5 years. The patients were either treated with TNFi (n=16), TNFi+MTX (n=36) or MTX (n=14). After the last TBE-vaccine dose, given one year after the first, 39% of the patients compared to 79% of the healthy controls had seroprotective levels (p=<0.05).

    CONCLUSIONS: Standard TBE-vaccine schedule does not confer enough immunogenicity in this group of immunosuppressed patients, who should be carefully informed about a higher risk for vaccination failure and risk of infection when exposed in high-endemic areas.

  • 8.
    Hjorton, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hellbacher, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sundstrom, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Lymphoma in Patients with Granulomatosis with Polyangiitis2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no Suppl 10, article id 869Article in journal (Other academic)
  • 9. Kaiser, Christina
    et al.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordström, Dan
    Pettersson, Tom
    Fransson, Jonas
    Florin-Robertsson, Ebba
    Pilström, Björn
    Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations2012In: Rheumatology International, ISSN 0172-8172, E-ISSN 1437-160X, Vol. 32, no 2, p. 295-299Article, review/survey (Refereed)
    Abstract [en]

    Anakinra (Kineret), a recombinant form of human interleukin-1 (IL-1) receptor antagonist, is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate. Kineret is self-administered by daily subcutaneous injections in patients with active RA. The mechanism of action of anakinra is to competitively inhibit the local inflammatory effects of IL-1. Kineret is generally safe and well tolerated and the only major treatment-related side effects that appear are skin reactions at the injection site. Due to the relatively short half-life of anakinra, daily injection of the drug is required. This, in combination with the comparably high rates of injection-site reactions (ISRs) associated with the drug, can become a problem for the patient. The present review summarises published data concerning ISRs associated with Kineret and provides some explanations as to their cause. The objective is also to present some clinical experiences of how the ISRs can be managed.

  • 10.
    Knight, A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hallenberg, H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Efficacy and safety of rituximab as maintenance therapy for relapsing granulomatosis with polyangiitis-a case series.2014In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 33, no 6, p. 841-848Article in journal (Refereed)
    Abstract [en]

    The objective of this work was to study the efficacy and safety of pre-emptive rituximab (RTX) in a series of patients with severe relapsing granulomatosis with polyangiitis (GPA). GPA is a systemic vasculitis with a high relapse rate despite successful remission induction. Drug toxicity with repeated induction treatments and long-standing immunosuppression poses a problem. Based on the findings in reports on RTX for rheumatoid arthritis, we treated patients with severe relapsing GPA with pre-emptive RTX, 1,000 mg 2 weeks apart every 6 months, aiming at achieving sustainable remission. All patients at one centre with relapsing GPA in spite of traditional maintenance treatment, who had received more than or equal to three cycles of RTX as regularly repeated pre-emptive maintenance therapy every 6 months, were included in this retrospective study. Information on disease manifestations and activity, treatments, lab parameters and adverse events was extracted from the medical files. Of the 12 included patients, all with a positive proteinase 3-anti-neutrophil cytoplasmic antibodies, generalised disease and a median disease duration of 35 months (21-270), 92 % (11/12) achieved sustainable remission during a median follow-up time of 32 months (range 21-111) from first RTX treatment. Concomitant immunosuppressants were reduced. Infections were the most common adverse events, but infections were an issue also before the start of RTX. RTX administered every 6 months seems to be an effective maintenance treatment in a population with severe, relapsing long-standing GPA. Granulomatous as well as vasculitic manifestations responded equally well. Infections are a problem in this patient group but no new safety problems were identified.

  • 11.
    Knight, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Askling, Johan
    Fredrik, Granath
    Pär, Sparen
    Ekbom, Anders
    Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide2004In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 63, no 10, p. 1307-1311Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis.

    METHODS:

    In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated.

    RESULTS:

    The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis.

    CONCLUSION:

    The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis.

  • 12.
    Knight, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Bruchfeld, A.
    Gunnarsson, I.
    Late-onset neutropaenia in ANCA-associated vasculitis after rituximab treatment2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, no S127, p. 50-51Article in journal (Other academic)
  • 13.
    Knight, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ekbom, Anders
    Brandt, Lena
    Askling, Johan
    Increasing Incidence of Wegener´s granulomatosis in Sweden 1975-20012006In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 33, no 10, p. 2060-2063Article in journal (Refereed)
    Abstract [en]

    Objective. Studies of Wegener's granulomatosis (WG) since the late 1980s indicate a probable increase in incidence of unknown cause and significance, possibly related to antineutrophil cytoplasmic antibody (ANCA) testing. To extend these observations and to include calendar periods before ANCA was introduced, we assessed time trends in the incidence of WG in Sweden in the period 1975-2001.

    Methods. In the population-based Swedish Inpatient Register, we identified 1938 individuals diagnosed with WG in the period 1975-2001, and calculated the annual age and sex adjusted incidences.

    Results. The incidence increased from 0.33 (95% CI 0.28-0.39) in the period 1975-85 to 0.77 (95% CI 0.69-0.85) in 1986-90, to 1.19 (95% CI 1.12-1.26) in 1991-2001, resulting in a mean incidence of 0.78 (95% CI 0.74-0.82).

    Conclusion. WG displays a strong temporal trend. While the increase coincides to some extent with the implementation of ANCA testing, suggestive of increased disease recognition, ANCA testing remains an incomplete explanation as increasing incidences were noted before as well as after their introduction.

  • 14.
    Knight, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Ekbom, Anders
    Brandt, Lena
    Askling, Johan
    What is the significance in routine care of c-ANCA/PR3-ANCA in the abscence of systemic vasculitis?: A case series2008In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 26, no 3, p. S53-S56Article in journal (Refereed)
    Abstract [en]

    Objective. ANCA has come to play an important role in diagnosing vasculitis. In selected populations c-ANCA/PR3-ANCA has a high specificity and sensitivity for vasculitis. In clinical practice, how individuals with c-ANCA/PR3-ANCA but without sufficient evidence of systemic vasculitis should be managed is unclear. We therefore retrospectively assessed the disease panorama and outcome in a consecutive series of individuals with c-ANCA/PR3-ANCA, and studied in detail those individuals who turned out not to fulfil criteria for vasculitic disease.

    Methods. The study population consisted of 74 consecutive patients who all had a positive test for C-ANCA and PR3-ANCA between 1992 and 2002 at the Immunology laboratory at Uppsala University Hospital, Sweden. The patients' medical files were reviewed and their diagnosis re-evaluated through June 2006.

    Results. 18 of the 74 ANCA-positive individuals did not present clinical evidence supportive of, or insufficient to support, a diagnosis of systemic vasculitis, but presented a range of other diseases. During a mean follow-up of 6.8 years, none of these 18 patients developed vasculitis.

    Conclusions. Individuals with a positive c-ANCA and PR3-ANCA but no vasculitis at the time of testing run an unknown but likely small risk of later developing vasculitis. In this group, a positive ANCA may represent background noise (borderline titres) or be a marker of inflammatory activity rather than of vasculitic disease (high titres).

  • 15.
    Knight, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hjorton, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Backlin, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Smedby, Karin E
    Askling, Johan
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Leukemia and Myelodysplastic Syndrome in Granulomatosis with Polyangiitis: Subtypes, Clinical Characteristics, and Outcome2015In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 4, p. 690-694Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Previous studies have shown that patients with granulomatosis with polyangiitis (GPA) have an increased risk of hematological malignancies, especially leukemia. Our aim was to assess clinical characteristics and treatment of patients with GPA complicated by hematological malignancies with focus on leukemia and to describe these malignancies in more detail.

    METHODS: From the Swedish population-based patient register, all individuals with a diagnosis of GPA from 1964-2012 were identified (n = 3224). Through linkage with the Swedish Cancer Register, we searched for all cases of leukemia [International Classification of Diseases (ICD) 7: 204-207 and corresponding codes ICD 8-10] registered after the first discharge listing GPA. The GPA diagnosis was evaluated using the European Medical Association classification algorithm. To confirm the hematological malignancy, all diagnostic bone marrow samples were reclassified. Clinical data of both the GPA and hematological malignancy were collected from medical files.

    RESULTS: Twenty-one cases were identified, all of myeloid origin, including 9 with myelodysplastic syndrome developing to acute myeloid leukemia (MDS-AML), 7 AML, 3 MDS, and 2 chronic myeloid leukemia. The median time from GPA diagnosis to hematological malignancy was 8 years (range 5-21). All patients had severe generalized GPA and had received high doses of cyclophosphamide (CYC; median cumulative dose 96.5 g). Cytopenia occurred in 76% of the patients prior to the hematological malignancy.

    CONCLUSION: The findings emphasize the longterm risk of leukemia and MDS in CYC-treated, severely ill patients with GPA. Cytopenia during the course of GPA may be a warning sign and warrants a liberal attitude toward bone marrow examination.

  • 16.
    Knight, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Pauksen, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eva, Kumlien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Fatal outcome of tick-borne encephalitis in two patients with rheumatic disease treated with rituximab2017In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56, no 5, p. 855-856Article in journal (Refereed)
  • 17.
    Knight, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sandin, Sven
    Askling, Johan
    Risks and relative risks of Wegener's granulomatosis among close relatives of patients with the disease2008In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 58, no 1, p. 302-7Article in journal (Other academic)
    Abstract [en]

    OBJECTIVE: The etiology of Wegener's granulomatosis (WG) supposedly involves interplay between genetic susceptibility and environmental triggers. However, little is known about whether WG actually clusters in families. Information on the degree of familial aggregation in WG is of clinical relevance, because patients with WG often want to know whether their diagnosis puts their closest relatives at increased risk of the disease. The aim of this study was to investigate the risk of WG in relatives of patients with WG. METHODS: Using Swedish nationwide registers on morbidity, family structure, and vital status, we compared the occurrence of WG (register-based plus chart review) among 6,670 first-degree relatives and 428 spouses of 1,944 Swedish patients with WG with the occurrence among 68,994 first-degree relatives and 4,812 spouses of 19,655 control subjects from the general population. Relative risks were estimated using the Cox proportional hazards regression model. RESULTS: Two of the 6,670 first-degree relatives of patients with WG and 13 of the 68,994 first-degree relatives of their population controls had WG, resulting in a relative risk of 1.56 (95% confidence interval 0.35-6.90). None of the 428 spouses of patients had WG. CONCLUSION: In absolute terms, the occurrence of WG among close biologic and nonbiologic relatives of patients with WG is low. In terms of relative risk, our results provide strong evidence against a pronounced increase in familial risk such as that noted for systemic lupus erythematosus, irritable bowel disease, and multiple sclerosis but are compatible with familial aggregation of a magnitude similar to that for rheumatoid arthritis.

  • 18.
    Lyons, Paul A.
    et al.
    Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England;Univ Cambridge, Jeffrey Cheah Biomed Ctr, Cambridge Inst Therapeut Immunol & Infect Dis, Cambridge CB2 0AW, England.
    Peters, James E.
    Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England;Univ Cambridge, Dept Publ Hlth & Primary Care, BHF Cardiovasc Epidemiol Unit, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England;Hlth Data Res UK, Cambridge, England.
    Alberici, Federico
    Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England;San Carlo Borromeo Hosp, Nephrol & Immunopathol Unit, ASST Santi Paolo & Carlo, Milan, Italy;Univ Milan, Dipartimento Sci Salute, Milan, Italy.
    Liley, James
    Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England;Cambridge Inst Publ Hlth, Med Res Council Biostat Unit, Cambridge Biomed Campus,Forvie Site,Robinson Way, Cambridge CB2 0SR, England.
    Coulson, Richard M. R.
    Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England.
    Astle, William
    Univ Cambridge, Dept Publ Hlth & Primary Care, BHF Cardiovasc Epidemiol Unit, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England;Cambridge Inst Publ Hlth, Med Res Council Biostat Unit, Cambridge Biomed Campus,Forvie Site,Robinson Way, Cambridge CB2 0SR, England;NHS Blood & Transplant, Long Rd,Cambridge Biomed Campus, Cambridge, England.
    Baldini, Chiara
    Univ Pisa, Rheumatol Unit, Pisa, Italy.
    Bonatti, Francesco
    Univ Hosp Parma, Unit Mol Genet, Via Gramsci 14, I-43126 Parma, Italy.
    Cid, Maria C.
    Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Dept Autoimmune Dis,CRB CELLEX, Barcelona, Spain.
    Elding, Heather
    Univ Cambridge, Natl Inst Hlth Res Blood & Transplant Unit Donor, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England;Wellcome Trust Sanger Inst, Dept Human Genet, Wellcome Trust Genome Campus, Cambridge CB10 1HH, England.
    Emmi, Giacomo
    Univ Firenze, Dept Expt & Clin Med, Florence, Italy.
    Epplen, Joerg
    Ruhr Univ Bochum, Human Genet, Bochum, Germany.
    Guillevin, Loic
    Hop Cochin, Serv Med Interne, F-75679 Paris 14, France.
    Jayne, David R. W.
    Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England.
    Jiang, Tao
    Univ Cambridge, Dept Publ Hlth & Primary Care, BHF Cardiovasc Epidemiol Unit, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England.
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.
    Lamprecht, Peter
    Univ Lubeck, Dept Rheumatol & Clin Immunol, D-23562 Lubeck, Germany.
    Leslie, Stephen
    Univ Melbourne, Sch Math & Stat, Parkville, Vic 3010, Australia;Univ Melbourne, Sch Biosci, Parkville, Vic 3010, Australia;Univ Melbourne, Melbourne Integrat Gen, Parkville, Vic 3010, Australia;Murdoch Childrens Res Inst, Data Sci, Parkville, Vic 3052, Australia.
    Little, Mark A.
    Tallaght Hosp, Trinity Translat Med Inst, Trinity Hlth Kidney Ctr, Dublin, Ireland.
    Martorana, Davide
    Univ Hosp Parma, Unit Mol Genet, Via Gramsci 14, I-43126 Parma, Italy.
    Moosig, Frank
    Rheumazentrum Schleswig Holstein Mitte, Neumunster, Germany.
    Neumann, Thomas
    Jena Univ Hosp, Dept Internal Med 3, Jena, Germany;Cantonal Hosp St Gallen, Dept Rheumatol Immunol & Rehabil, St Gallen, Switzerland.
    Ohlsson, Sophie
    Lund Univ, Div Clin Sci, Dept Nephrol, Lund, Sweden.
    Quickert, Stefanie
    Jena Univ Hosp, Dept Internal Med 3, Jena, Germany;Jena Univ Hosp, Dept Internal Med Gastroenterol Hepatol & Infect, Jena, Germany.
    Ramirez, Giuseppe A.
    Univ Vita Salute San Raffaele, Unit Immunol Rheumatol Allergy & Rare Dis, Milan, Italy;IRCCS Osped San Raffaele, Milan, Italy.
    Rewerska, Barbara
    Jagiellonian Univ, Med Coll, Krakow, Poland.
    Schett, Georg
    Friedrich Alexander Univ Erlangen Nuremberg, Dept Internal Med Rheumatol & Immunol 3, Erlangen, Germany;Univ Klinikum Erlangen, Erlangen, Germany.
    Sinico, Renato A.
    Univ Milano Bicocca, Sch Med & Surg, Dept Med & Surg, Via Cadore 48, I-20900 Monza, Italy.
    Szczeklik, Wojciech
    Jagiellonian Univ, Med Coll, Krakow, Poland.
    Tesar, Vladimir
    Charles Univ Prague, Fac Med 1, Dept Nephrol, Prague, Czech Republic;Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic.
    Vukcevic, Damjan
    Univ Melbourne, Sch Math & Stat, Parkville, Vic 3010, Australia;Univ Melbourne, Sch Biosci, Parkville, Vic 3010, Australia;Univ Melbourne, Melbourne Integrat Gen, Parkville, Vic 3010, Australia;Murdoch Childrens Res Inst, Data Sci, Parkville, Vic 3052, Australia.
    Akil, Mohammed
    Sheffield Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England.
    Barratt, Jonathan
    Univ Leicester, Dept Infect Immun & Inflammat, Leicester LE1 9HN, Leics, England.
    Basu, Neil
    Univ Glasgow, Inst Infect Immunol & Inflammat, Glasgow, Lanark, Scotland.
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, BHF Cardiovasc Epidemiol Unit, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England;Hlth Data Res UK, Cambridge, England;Univ Cambridge, Natl Inst Hlth Res Blood & Transplant Unit Donor, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England.
    Bruce, Ian
    Manchester Univ Hosp NHS Fdn Trust, NIHR Manchester Musculoskeletal Biomed Res Ctr, Manchester, Lancs, England;Univ Manchester, Manchester Acad Hlth Sci Ctr, Ctr Musculoskeletal Res, Ctr Epidemiol Versus Arthrit, Manchester, Lancs, England.
    Clarkson, Michael
    Cork Univ Hosp, Cork, Ireland.
    Conlon, Niall
    St James Hosp Dublin, Dept Immunol, Dublin, Ireland.
    DasGupta, Bhaskar
    Southend Univ Hosp, Westcliff On Sea SS0 0RY, England.
    Doulton, Timothy W. R.
    East Kent Hosp Univ NHS Fdn Trust, Kent & Canterbury Hosp, Canterbury CT1 3NG, Kent, England.
    Espigol-Frigole, Georgina
    Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Dept Autoimmune Dis,CRB CELLEX, Barcelona, Spain.
    Flossmann, Oliver
    Royal Berkshire Hosp NHS Trust, Reading RG1 5AN, Berks, England.
    Gabrielli, Armando
    Osped Riuniti Univ, Politecn Marche, Dept Internal Med, Ancona, Italy.
    Gasior, Jolanta
    Univ Hosp, Dept Allergy & immunol, Krakow, Poland.
    Gregorini, Gina
    Spedali Civil Brescia, Nephrol Unit, Brescia, Italy.
    Guida, Giuseppe
    ASL TO2 Birago Vische Hosp, Med Sci Dept, Internal Med Immunol & Allergol Outpatient Clin 2, Turin, Italy;Univ Torino, Turin, Italy.
    Hernandez-Rodriguez, Jose
    Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Dept Autoimmune Dis,CRB CELLEX, Barcelona, Spain.
    Hruskova, Zdenka
    Charles Univ Prague, Fac Med 1, Dept Nephrol, Prague, Czech Republic;Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic.
    Hudson, Amy
    Murdoch Childrens Res Inst, Data Sci, Parkville, Vic 3052, Australia.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Lanyon, Peter
    Nottingham Univ Hosp NHS Trust, Nottingham NG7 2UH, England.
    Luqmani, Raashid
    Nuffield Orthopaed Ctr, Oxford OX3 7LD, England.
    Magliano, Malgorzata
    Stoke Mandeville Hosp, Aylesbury HP21 8AL, Bucks, England.
    Manfredi, Angelo A.
    Univ Vita Salute San Raffaele, Unit Immunol Rheumatol Allergy & Rare Dis, Milan, Italy;IRCCS Osped San Raffaele, Milan, Italy.
    Marguerie, Christopher
    South Warwickshire NHS Fdn Trust, Warwick, England.
    Maritati, Federica
    Univ Firenze, Dept Biomed Expt & Clin Sci Mario Serio, Florence, Italy;Meyer Childrens Hosp, Florence, Italy.
    Marvisi, Chiara
    Univ Firenze, Dept Biomed Expt & Clin Sci Mario Serio, Florence, Italy;Meyer Childrens Hosp, Florence, Italy.
    McHugh, Neil J.
    Royal Natl Hosp Rheumat Dis, Bath BA1 1RL, Avon, England.
    Molloy, Eamonn
    St Vincents Hosp Dublin, Dublin, Ireland.
    Motyer, Allan
    Univ Melbourne, Sch Math & Stat, Parkville, Vic 3010, Australia;Univ Melbourne, Sch Biosci, Parkville, Vic 3010, Australia;Univ Melbourne, Melbourne Integrat Gen, Parkville, Vic 3010, Australia.
    Mukhtyar, Chetan
    Norfolk & Norwich Univ Hosp, Norwich NR4 7UY, Norfolk, England.
    Padyukov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.
    Pesci, Alberto
    Univ Milano Bicocca, Pneumol Unit, Milan, Italy.
    Prieto-Gonzalez, Sergio
    Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Dept Autoimmune Dis,CRB CELLEX, Barcelona, Spain.
    Ramentol-Sintas, Marc
    Hosp Valle De Hebron, Vall dHebron Res Inst, Res Unit System Autoimmune Dis, Barcelona, Spain.
    Reis, Petra
    Friedrich Alexander Univ Erlangen Nuremberg, Dept Internal Med Rheumatol & Immunol 3, Erlangen, Germany;Univ Klinikum Erlangen, Erlangen, Germany.
    Roccatello, Dario
    Univ Torino, Ctr Res Immunopathol & Rare Dis, Dept Rare Immunol Hematol & Immunohematol Dis, Turin, Italy.
    Rovere-Querini, Patrizia
    Jena Univ Hosp, Dept Internal Med Gastroenterol Hepatol & Infect, Jena, Germany.
    Salvarani, Carlo
    Azienda USL IRCCS Reggio Emilia, Reggio Emilia, Italy;Univ Modena & Reggio Emilia, Reggio Emilia, Italy.
    Santarsia, Francesca
    Univ Hosp Parma, Nephrol Unit, Parma, Italy.
    Solans-Laque, Roser
    Hosp Valle De Hebron, Vall dHebron Res Inst, Res Unit System Autoimmune Dis, Barcelona, Spain.
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Dept Human Genet, Wellcome Trust Genome Campus, Cambridge CB10 1HH, England;Univ Cambridge, Dept Haematol, Cambridge Biomed Campus, Cambridge CB2 0PT, England.
    Taylor, Jo
    Dorset Cty Hosp, Dorchester DT1 2JY, England.
    Wessels, Julie
    Royal Stoke Univ Hosp, Stoke On Trent ST4 6QG, Staffs, England.
    Zwerina, Jochen
    Friedrich Alexander Univ Erlangen Nuremberg, Dept Internal Med Rheumatol & Immunol 3, Erlangen, Germany;Univ Klinikum Erlangen, Erlangen, Germany.
    Terrier, Benjamin
    Hop Cochin, Serv Med Interne, F-75679 Paris 14, France.
    Watts, Richard A.
    Ipswich Hosp, Dept Rheumatol, Heath Rd, Ipswich IP4 5PD, Suffolk, England;Univ East Anglia, Norwich Med Sch, Norwich NR7 4TJ, Norfolk, England.
    Vaglio, Augusto
    Univ Firenze, Dept Biomed Expt & Clin Sci Mario Serio, Florence, Italy;Meyer Childrens Hosp, Florence, Italy.
    Holle, Julia U.
    Rheumazentrum Schleswig Holstein Mitte, Neumunster, Germany.
    Wallace, Chris
    Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England;Univ Cambridge, Jeffrey Cheah Biomed Ctr, Cambridge Inst Therapeut Immunol & Infect Dis, Cambridge CB2 0AW, England;Cambridge Inst Publ Hlth, Med Res Council Biostat Unit, Cambridge Biomed Campus,Forvie Site,Robinson Way, Cambridge CB2 0SR, England.
    Smith, Kenneth G. C.
    Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England;Univ Cambridge, Jeffrey Cheah Biomed Ctr, Cambridge Inst Therapeut Immunol & Infect Dis, Cambridge CB2 0AW, England.
    Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status2019In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 5120Article in journal (Refereed)
    Abstract [en]

    Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.

  • 19. Nordström, Dan
    et al.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Luukkainen, Reijo
    van Vollenhoven, Ronald
    Rantalaiho, Vappu
    Kajalainen, Anna
    Brun, Johan G.
    Proven, Anne
    Ljung, Lotta
    Kautiainen, Hannu
    Pettersson, Tom
    Beneficial Effect of Interleukin 1 Inhibition with Anakinra in Adult-onset Still's Disease. An Open, Randomized, Multicenter Study2012In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 39, no 10, p. 2008-2011Article in journal (Refereed)
    Abstract [en]

    Objective. To study the efficacy of anakinra versus disease-modifying antirheumatic drugs (DMARD) in refractory adult-onset Still's disease (AOSD). Methods. In a 24-week study, 22 patients with AOSD taking prednisolone >= 10 mg/day received anakinra (n = 12) or DMARD (n = 10). The primary endpoint was achievement of remission. Results. At 8 and 24 weeks, 7/12 and 6/12 receiving anakinra and 5/10 and 2/10 receiving DMARD achieved remission. Anakinra induced greater improvement in physical health measured by Medical Outcomes Study Short-Form 36 (SF-36; p < 0.011). During an open-label extension (OLE) of 28 weeks, 7/14 patients taking anakinra and 2/3 taking DMARD were in remission. Conclusion. Anakinra induced more beneficial responses than DMARD in patients with AOSD and was favored in the OLE phase. (ClinicalTrials.gov Protocol Registration NCT01033656).

  • 20.
    Sohrabian, Azita
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mathsson Alm, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Thermo Fisher Sci, ImmunoDiagnost Div, Uppsala, Sweden..
    Hansson, M.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Lysholm, J.
    Falun Cent Hosp, Clin Rheumatol, Falun, Sweden..
    Cornillet, M.
    Toulouse Univ, INSERM, U1056, Epithelial Differentiat & Rheumatoid Autoimmun, Toulouse, France..
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Skriner, K.
    Charite, Dept Med, Berlin, Germany..
    Serre, G.
    Toulouse Univ, INSERM, U1056, Epithelial Differentiat & Rheumatoid Autoimmun, Toulouse, France..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Weitoft, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Number Of Peptide-Specific Anti-Citrullinated Peptide Antibodies In Synovial Fluid And In Synovial Fluid Immune Complexes Associate With Degree Of Radiological Destruction And Response To Triamcinolone Hexacetonide For Knee Synovitis In Rheumatoid Arthritis2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 509-510Article in journal (Other academic)
  • 21.
    Sohrabian, Azita
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mathsson Alm, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Hansson, Monika
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Lysholm, Jörgen
    Falun Cent Hosp, Clin Rheumatol, Falun, Sweden.
    Cornillet, Martin
    Toulouse Univ, Lab Epithelial Differentiat & Rheumatoid Autoimmu, INSERM, U1056, Toulouse, France.
    Skriner, Karl
    Charite, Dept Med, Berlin, Germany.
    Serre, Guy
    Toulouse Univ, Lab Epithelial Differentiat & Rheumatoid Autoimmu, INSERM, U1056, Toulouse, France.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Weitoft, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, no 9, p. 1345-1353Article in journal (Refereed)
    Abstract [en]

    Introduction: Individual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.

    Methods: We have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.

    Results: The majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.

    Conclusions: Our data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.

  • 22.
    Turesson, C.
    et al.
    Lund Univ, Dept Clin Sci, Rheumatol, Malmo, Sweden;Skane Univ Hosp, Dept Rheumatol, S-20502 Malmo, Sweden.
    Börjesson, O.
    Karolinska Univ Hosp, Dept Rheumatol, Stockholm, Sweden.
    Larsson, K.
    Sahlgrens Univ Hosp, Dept Rheumatol, Gothenburg, Sweden.
    Mohammad, A. J.
    Lund Univ, Dept Clin Sci, Rheumatol, Lund, Sweden;Skane Univ Hosp, Dept Rheumatol, Lund, Sweden.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Swedish Society of Rheumatology 2018 guidelines for investigation, treatment, and follow-up of giant cell arteritis2019In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 48, no 4, p. 259-265Article, review/survey (Refereed)
    Abstract [en]

    Objective: To develop evidence-based guidelines for the management of giant cell arteritis (GCA) as a complement to guidelines in other areas of rheumatology, issued by the Swedish Society of Rheumatology.

    Methods: A working group selected key areas for recommendations, reviewed the available evidence, and wrote draft guidelines. These were discussed and revised according to standard procedures within the Swedish Society of Rheumatology, including a one-day meeting open to all members. For key recommendations, the quality of evidence was assessed according to GRADE. The final guidelines were approved by the Society board in March 2018.

    Results: The guidelines include recommendations on diagnostic procedures, pharmacological treatment, follow-up, and adjuvant treatment. Ultrasonography is complementary to temporal artery biopsy (TAB) in the diagnostic work-up. Other imaging techniques (magnetic resonance imaging and positron emission tomography/computed tomography) are important in evaluating large-vessel involvement. Glucocorticoids (oral, or intravenous in cases with ischaemic complications) remain the first line treatment for GCA. Addition of tocilizumab is recommended for patients with relapsing disease who meet five criteria, representing active disease that has been objectively verified by TAB or imaging. Tocilizumab may also be considered in patients with newly diagnosed GCA who are at major risk of severe glucocorticoid side effects. Based on current evidence, tocilizumab treatment for >1 year cannot be recommended.

    Conclusion: These guidelines are based on current evidence and consensus within Swedish rheumatology. Following major developments in diagnostics and treatment of GCA, such guidelines are important for clinical practice, and should be updated on a regular basis.

  • 23.
    Weitoft, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Manivel, Vivek A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lysholm, Jörgen
    Clinic of Rheumatology, Falun Hospital, Falun.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies2015In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, no 10, p. 1923-1928Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RA patients with and without ACPA and RF.

    METHODS: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3.

    RESULTS: SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients.

    CONCLUSION: The differences in cathepsin S and cathepsin L between RA patients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.

  • 24.
    Weitoft, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Saxne, T
    Lund University, Department of Clinical Sciences, Section of Rheumatology.
    Manivel, Vivek Anand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lysholm, J
    Falun Hospital, Clinic of Rheumatology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Pentraxin 3 in serum and synovial fluid of patients with rheumatoid arthritis with and without autoantibodies2017In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 46, no 5, p. 346-352Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Pentraxin 3 (PTX3) is a locally produced multifunctional protein involved in inflammation, matrix deposition, and immunity. As patients with seropositive rheumatoid arthritis (RA) have a more severe disease course and higher risk of joint destruction than seronegative patients, the aim of the present study was to examine differences in PTX3 in synovial fluid (SF) (and serum) in seropositive compared to seronegative RA, and other local markers of inflammation and destruction.

    METHOD:

    Ninety-seven RA patients with knee effusion were included. Serum and SF levels of PTX3, as well as serum levels of anti-citrullinated protein antibody and rheumatoid factor of immunoglobulin A and M subclasses, and markers of inflammation and potential destruction in SF: white blood cell counts, tumour necrosis factor, interleukin-6, vascular endothelial growth factor, metalloproteinase 3, and cartilage oligomeric matrix protein, were analysed. In addition, a radiographic knee examination was performed.

    RESULTS:

    Seropositive patients had significantly higher PTX3 levels in SF than seronegative patients, whereas there was no difference for serum levels. SF-PTX3 levels correlated with disease activity and with local inflammatory markers, especially polymorphonuclear cells, and with autoantibody levels. There was no correlation between PTX3 levels in serum and SF.

    CONCLUSION:

    The correlation of disease activity and autoantibody levels with SF-PTX3 levels in antibody-positive patients suggests a role for PTX3 in the inflammatory process specifically in seropositive RA joints, and supports the hypothesis that seropositive and seronegative RA are different disease entities. Polymorphonuclear granulocytes may be an important source of PTX3 in RA SF.

  • 25.
    Weitoft, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Lysholm, Jörgen
    Saxne, Tore
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Outcome predictors of intra-articular glucocorticoid treatment for knee synovitis in patients with rheumatoid arthritis: a prospective cohort study2014In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 16, no 3, p. R129-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Intra-articular glucocorticoid treatment (IAGC) is widely used for symptom relief in arthritis. However, knowledge of factors predicting treatment outcome is limited. The aim of the present study was to identify response predictors of IAGC for knee synovitis in patients with rheumatoid arthritis (RA).

    METHODS:

    In this study 121 RA patients with synovitis of the knee were treated with intra-articular injections of 20 mg triamcinolone hexacetonide. They were followed for 6 months and the rate of clinical relapse was studied. Non-responders (relapse within 6 months) and responders were compared regarding patient characteristics and knee joint damage as determined by the Larsen-Dale index. In addition, matched samples of serum and synovial fluid were analyzed for factors reflecting the inflammatory process (C-reactive protein, interleukin 6, tumour necrosis factor alpha, vascular endothelial growth factor), joint tissue turnover (cartilage oligomeric matrix protein, metalloproteinase 3), and autoimmunity (antinuclear antibodies, antibodies against citrullinated peptides, rheumatoid factor).

    RESULTS:

    During the observation period, 48 knees relapsed (40%). Non-responders had more radiographic joint damage than responders (p = 0.002) and the pre-treatment vascular endothelial growth factor (VEGF) level in synovial fluid was significantly higher in non-responders (p = 0.002).

    CONCLUSIONS:

    Joint destruction is associated with poor outcome of IAGC for knee synovitis in RA. In addition, higher levels of VEGF in synovial fluid are found in non-responders, suggesting that locally produced VEGF is a biomarker for recurrence of synovial hyperplasia and the risk for arthritis relapse.

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