uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 53) Show all publications
Sabre, L., Evoli, A. & Rostedt Punga, A. (2019). Cognitive dysfunction in mice with passively induced MuSK antibody seropositive myasthenia gravis. Journal of the Neurological Sciences, 399, 15-21
Open this publication in new window or tab >>Cognitive dysfunction in mice with passively induced MuSK antibody seropositive myasthenia gravis
2019 (English)In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 399, p. 15-21Article in journal (Refereed) Published
Abstract [en]

Recent reports on cognitive dysfunction, in addition to skeletal muscle fatigue, in muscle-specific tyrosine kinase antibody seropositive (MuSK+) myasthenia gravis (MG) patients led us to study cognition in mice with MuSK+passive transfer MG (PTMG). Twelve 7-week-old female wild-type C57BL/6J mice were passively immunized with IgG from MuSK+ MG patients and 12 control mice received intraperitoneal saline injections. Mice were evaluated with clinical, neurophysiological and behavioral tests (Barnes maze (BM) and novel object recognition (NOR)), and the muscles were immunostained to evaluate the neuromuscular junction in the end of the study. Two-thirds of the immunized mice developed clinically distinct MuSK + PTMG. MuSK + PTMG mice spent less time exploring the novel object in the NOR test (MuSK+ mice 36.4% +/- 14.0 vs controls 52.4% +/- 13.0, p = .02), unrelated to the muscle weakness and regardless of rodents' innate preference of novelty. In the BM test, control mice were more eager to use the direct strategy than the MuSK+ mice (MuSK+ 17.3% vs controls 29.5%, p = .02). Our findings shed new light on cognition dysfunction in human MuSK + MG patients and indicate that recognition memory in the perirhinal cortex could be affected in MuSK + MG.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2019
Keywords
MuSK, Myasthenia, Mice, Cognitive dysfunction, Behavioral, Hippocampus
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-383198 (URN)10.1016/j.jns.2019.02.001 (DOI)000465148900004 ()30738333 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2019-07-23 Created: 2019-07-23 Last updated: 2019-07-23Bibliographically approved
Rostedt Punga, A., Jabre, J. F. & Amandusson, Å. (2019). Facing the challenges of electrodiagnostic studies in the very elderly (>80 years) population. Clinical Neurophysiology, 130(7), 1091-1097
Open this publication in new window or tab >>Facing the challenges of electrodiagnostic studies in the very elderly (>80 years) population
2019 (English)In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 130, no 7, p. 1091-1097Article in journal (Refereed) Published
Abstract [en]

Objective: Studies on electrodiagnostic (EDX) methods usually exclude the very elderly. This also holds true for studies of normal EDX values. We analyzed the outcome and diagnostic value of EDX and collected reference data in a large cohort of patients >= 80 years of age. Methods: Referral information, ICD-10 diagnoses and EDX data were retrieved from all patients >= 80 years of age referred for EDX studies at our department in 1995-2015. Normative data, including reference ranges, were obtained using the extrapolated norms (e-norms) method. Results: 1966 unique patients (2335 examinations) were included. Only 11% were considered to have normal findings. 66% had pathological EDX findings in accordance with the indication for referral. Carpal tunnel syndrome was by far the most common diagnosis. Normative data retrieved using e-norms were similar to those of reference values from healthy subjects regarding EMG multiMUP data, but typically provided a wider normality window when applied to nerve conduction parameters. Conclusions: EDX studies are valuable in the diagnostic work-up of very elderly patients. Using the e-norms method may be a useful alternative when obtaining reference values in this age group. Significance: Our findings provide additional insights to the challenges of evaluating very elderly patients with neuromuscular disease and underline the importance of including this growing part of the patient population in EDX research.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2019
Keywords
EDX, Very old, E-norms, EMG, Nerve conduction study, Aging
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-386429 (URN)10.1016/j.clinph.2019.03.029 (DOI)000469338500003 ()31078985 (PubMedID)
Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-06-25Bibliographically approved
Bränn, E., Edvinsson, Å., Rostedt Punga, A., Sundström Poromaa, I. & Skalkidou, A. (2019). Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum. Scientific Reports, 9, Article ID 1863.
Open this publication in new window or tab >>Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum
Show others...
2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 1863Article in journal (Refereed) Published
Abstract [en]

During pregnancy, the woman's body undergoes tremendous changes in immune system adaptation. The immunological shifts that occur in pregnancy can partially be explained by alterations in hormonal levels. Furthermore, during pregnancy, many autoimmune diseases go into remission, only to flare again in the early postpartum period. Given these important changes in the clinical course of a number of autoimmune disorders, surprisingly little has been done to investigate the inflammatory profile changes across pregnancy and the postpartum period. Thus, the aim of this study was to describe how inflammatory and anti-inflammatory markers change from late pregnancy to the early postpartum period, using a multiplexed assay consisting of both well-known as well as exploratory proteins. Two-hundred-and-ninety women were included in this study and donated a total of 312 blood samples; 198 in late pregnancy (similar to gw38) and 114 in the postpartum period (similar to w8). The plasma blood samples were analyzed for 92 immune system related protein markers using Proseek Multiplex Inflammation I panel, a high-sensitivity assay based on proximity extension assay technology. Fifty-six inflammatory and anti-inflammatory markers were significantly different between pregnancy and the postpartum, of which 50 survived corrections for multiple comparisons. Out of these 50 markers, 41 decreased from pregnancy to postpartum, while the remaining 9 increased in the postpartum period. The top five markers with the greatest decrease in the postpartum period were Leukemia inhibitory factor receptor (LIF-R), Latency-associated peptide Transforming growth factor beta-1 (LAP TGF-beta-1), C-C motif chemokine 28 (CCL28), Oncostatin M (OSM) and Fibroblast growth factor 21 (FGF21). Top three markers that increased in the postpartum period were Tumor necrosis factor ligand superfamily member 11 (TRANCE), Tumor necrosis factor ligand superfamily member 12 (TWEAK), and C-C motif chemokine/Eotaxin (CCL11). This study revealed that the majority of the markers decreased from pregnancy to postpartum, and only a few increased. Several of the top proteins that were higher in pregnancy than postpartum have anti-inflammatory and immune modulatory properties promoting pregnancy progress. These results clearly reflect the tremendous change in the immune system in the pregnancy to postpartum transition.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-378379 (URN)10.1038/s41598-018-38304-w (DOI)000458401500066 ()30755659 (PubMedID)
Funder
Swedish Research Council, VR:521-2013-2339Swedish Research Council, 523-2014-2342Marianne and Marcus Wallenberg Foundation
Available from: 2019-03-05 Created: 2019-03-05 Last updated: 2019-03-05Bibliographically approved
Bogatikov, E., Lindblad, I., Punga, T. & Rostedt Punga, A. (2019). miR-1933-3p is upregulated in skeletal muscles of MuSK+ EAMG mice and affects Impa1 and Mrpl27.. Neuroscience research, Article ID S0168-0102(18)30649-7.
Open this publication in new window or tab >>miR-1933-3p is upregulated in skeletal muscles of MuSK+ EAMG mice and affects Impa1 and Mrpl27.
2019 (English)In: Neuroscience research, ISSN 0168-0102, E-ISSN 1872-8111, article id S0168-0102(18)30649-7Article in journal, Editorial material (Refereed) Published
Abstract [en]

MuSK antibody seropositive (MuSK+) Myasthenia Gravis (MG) typically affects skeletal muscles of the bulbar area, including the omohyoid muscle, causing focal fatigue, weakness and atrophy. The profile of circulating extracellular microRNA (miRNA) is changed in MuSK + MG, but the intracellular miRNA profile in skeletal muscles of MuSK + MG and MuSK + experimental autoimmune MG (EAMG) remains unknown. This study elucidated the intracellular miRNA profile in the omohyoid muscle of mice with MuSK + EAMG. The levels of eleven mouse miRNAs were elevated and two mouse miRNAs were reduced in muscles of MuSK + EAMG mice. Transient expression of miR-1933-3p and miR-1930-5p in mouse muscle (C2C12) cells revealed several downregulated genes, out of which five had predicted binding sites for miR-1933-3p. The mRNA expression of mitochondrial ribosomal protein L27 (Mrpl27) and Inositol monophosphatase I (Impa1) was reduced in miR-1933-3p transfected C2C12 cells compared to control cells (p = 0.032 versus p = 0.020). Further, transient expression of miR-1933-3p reduced Impa1 protein accumulation in C2C12 cells. These findings provide novel insights of dysregulated miRNAs and their intracellular pathways in muscle tissue afflicted with MuSK + EAMG, providing a possible link to mitochondrial dysfunction and muscle atrophy observed in MuSK + MG.

Keywords
EAMG, Experimental autoimmune myasthenia gravis, MuSK antibody, miR-1933-3p, microRNA
National Category
Cell Biology
Identifiers
urn:nbn:se:uu:diva-395566 (URN)10.1016/j.neures.2019.02.003 (DOI)30763589 (PubMedID)
Available from: 2019-10-21 Created: 2019-10-21 Last updated: 2019-10-23
Sabre, L., Maddison, P., Wong, S. H., Sadalage, G., Ambrose, P. A., Plant, G. T. & Rostedt Punga, A. (2019). miR-30e-5p as predictor of generalization in ocular myasthenia gravis. Annals of clinical and translational neurology, 6(2), 243-251
Open this publication in new window or tab >>miR-30e-5p as predictor of generalization in ocular myasthenia gravis
Show others...
2019 (English)In: Annals of clinical and translational neurology, E-ISSN 2328-9503, Vol. 6, no 2, p. 243-251Article in journal (Refereed) Published
Abstract [en]

Objective: To determine a predictive factor for the risk of conversion from ocular myasthenia gravis (OMG) to generalized MG (GMG) in a prospective study.

Methods: RNA was isolated from serum samples and detection of microRNA (miRNA) expression analyzed with qPCR. In the discovery set, 179 human miRNAs were assayed for profiling of five OMG patients and four age- and gender-matched healthy controls. Based on the specific accumulation pattern of 19 miRNAs from the discovery set, in addition to miRNAs previously found elevated in generalized MG (GMG; miR-150-5p and miR-30e-5p), 21 miRNAs were subsequently analyzed in a validation cohort of 83 OMG patients (82 immunosuppression treatment naive; 49 male) within 3 months of diagnosis and at a follow-up visit (median duration 28 months from first visit).

Results: Thirteen patients generalized 14.8 +/- 12.0 months after the diagnosis and the majority (85%) belonged to the late onset MG group. Two miRNAs were significantly higher in secondary GMG (SGMG) patients compared to OMG patients with late onset MG: miR-30e-5p (9.1 +/- 0.5 vs. 6.3 +/- 0.9; P < 0.0001) and miR-150-5p (7.4 +/- 1.1 vs. 6.4 +/- 1.1; P = 0.01). The sensitivity for miR-30e-5p in differentiating OMG and SGMG was 96% in all OMG patients and 100% in late onset OMG patients.

Interpretation: This is the first study to describe a potential predictive factor associated with the risk of generalization for patients with OMG. Raised levels (>8) of miR-30e-5p at initial presentation in patients with ocular MG symptoms, give a predictive cut-off for subsequent generalization of 96-100%.

Place, publisher, year, edition, pages
WILEY, 2019
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-379273 (URN)10.1002/acn3.692 (DOI)000459708100004 ()30847357 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2019-03-18 Created: 2019-03-18 Last updated: 2019-03-18Bibliographically approved
Wang, S., Breskovska, I., Gandhy, S., Rostedt Punga, A., Guptill, J. T. & Kaminski, H. J. (2018). Advances in autoimmune myasthenia gravis management. Expert Review of Neurotherapeutics, 18(7), 573-588
Open this publication in new window or tab >>Advances in autoimmune myasthenia gravis management
Show others...
2018 (English)In: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 18, no 7, p. 573-588Article, review/survey (Refereed) Published
Abstract [en]

Introduction: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with no cure and conventional treatments limited by significant adverse effects and variable benefit. In the last decade, therapeutic development has expanded based on improved understanding of autoimmunity and financial incentives for drug development in rare disease. Clinical subtypes exist based on age, gender, thymic pathology, autoantibody profile, and other poorly defined factors, such as genetics, complicate development of specific therapies.

Areas covered: Clinical presentation and pathology vary considerably among patients with some having weakness limited to the ocular muscles and others having profound generalized weakness leading to respiratory insufficiency. MG is an antibody-mediated disorder dependent on autoreactive B cells which require T-cell support. Treatments focus on elimination of circulating autoantibodies or inhibition of effector mechanisms by a broad spectrum of approaches from plasmapheresis to B-cell elimination to complement inhibition.

Expert commentary: Standard therapies and those under development are disease modifying and not curative. As a rare disease, clinical trials are challenged in patient recruitment. The great interest in development of treatments specific for MG is welcome, but decisions will need to be made to focus on those that offer significant benefits to patients.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Myasthenia gravis, clinical trials, mycophenolate, tacrolimus, prednisone, eculizumab, rituximab, interleukins, plasma cells, acetylcholine receptor antibody, muscle-specific kinase
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369229 (URN)10.1080/14737175.2018.1491310 (DOI)000445623100005 ()29466933 (PubMedID)
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
Sabre, L., Maddison, P., Sadalage, G., Ambrose, P. A. & Rostedt Punga, A. (2018). Circulating microRNA miR-21-5p, miR-150-5p and miR-30e-5p correlate with clinical status in late onset myasthenia gravis. Journal of Neuroimmunology, 321, 164-170
Open this publication in new window or tab >>Circulating microRNA miR-21-5p, miR-150-5p and miR-30e-5p correlate with clinical status in late onset myasthenia gravis
Show others...
2018 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 321, p. 164-170Article in journal (Refereed) Published
Abstract [en]

There are no biomarkers for late onset myasthenia gravis (LOMG; onset > 50 years). We evaluated circulating microRNA in a discovery cohort of 4 LOMG patients and 4 healthy controls and in a prospective diagnostic validation cohort of 73 LOMG patients (48 male) with longitudinal follow-up samples. In immunosuppression naive patients, levels of miRNAs miR-150-5p, miR-21-5p and miR-30e-5p decreased in parallel with clinical improvement after initiation of immunosuppression and their levels positively correlated with the clinical MG composite score. Levels of miR-150-5p and miR-21-5p were lower in patients with ocular compared to generalized LOMG. Circulating miR-150-5p, miR-21-5p and miR-30e-5p correlate with the clinical course in LOMG.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2018
Keywords
Myasthenia gravis, LOMG, microRNA, miR-150-5p, MGC
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-361028 (URN)10.1016/j.jneuroim.2018.05.003 (DOI)000438322000021 ()29804819 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21Bibliographically approved
Sabre, L., Guptill, J. T., Russo, M., Juel, V. C., Massey, J. M., Howard, J. F. ., . . . Rostedt Punga, A. (2018). Circulating microRNA plasma profile in MuSK plus myasthenia gravis. Journal of Neuroimmunology, 325, 87-91
Open this publication in new window or tab >>Circulating microRNA plasma profile in MuSK plus myasthenia gravis
Show others...
2018 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 325, p. 87-91Article in journal (Refereed) Published
Abstract [en]

Muscle-specific tyrosine kinase antibody positive myasthenia gravis (MuSK+ MG) is an immunological subtype with distinctive pathogenic mechanisms and clinical features. The aim of this study was to analyze the circulating plasma microRNA profile of patients with MuSK + MG. From the discovery cohort miR-210-3p, miR-3243p and miR-328-3p were further analyzed in the validation cohort. We found a distinct plasma profile of miR210-3p and miR-324-3p that were significantly decreased in MuSK+ MG patients compared to healthy controls (4.1 +/- 1.4 vs 5.1 +/- 1.4, p = .006 and 4.7 +/- 1.0 vs 5.4 +/- 1.3, p = .02). These findings reveal a distinct plasma miRNA profile in MuSK+ MG.

Keywords
Muscle-specific tyrosine kinase, MuSK, Myasthenia gravis, microRNA, Biomarker
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-372925 (URN)10.1016/j.jneuroim.2018.10.003 (DOI)000452932200013 ()30316681 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-10Bibliographically approved
Rostedt Punga, A. & Punga, T. (2018). Circulating microRNAs as potential biomarkers in myasthenia gravis patients.. Annals of the New York Academy of Sciences, 1412(1), 33-40
Open this publication in new window or tab >>Circulating microRNAs as potential biomarkers in myasthenia gravis patients.
2018 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1412, no 1, p. 33-40Article, review/survey (Refereed) Published
Abstract [en]

MicroRNAs (miRNAs) are small noncoding RNA molecules that bind to specific mRNA targets and regulate a wide range of important biological processes within cells. Circulating miRNAs are released into the extracellular space and can be measured in most biofluids, including blood serum and plasma. Recently, circulating miRNAs have emerged as easily accessible markers in various body fluids with different profiles and quantities specific for different human disorders, including autoimmune diseases. In myasthenia gravis (MG), diagnostic tests such as titers of serum autoantibodies specific for either the acetylcholine receptor (AChR+) or muscle‐specific tyrosine kinase (MuSK+) do not necessarily reflect disease progression, and there is a great need for reliable objective biomarkers to monitor the disease course and therapeutic response. Recent studies in AChR+ MG revealed elevated levels of the immuno‐miRNAs miR‐150‐5p and miR‐21‐5p. Of particular importance, levels of miR‐150‐5p were lower in immunosuppressed patients and in patients with clinical improvement following thymectomy. In MuSK+ MG, another profile of circulating miRNAs was found, including upregulation of the let‐7 family of miRNAs. Here, we summarize the potential role of circulating miRNAs as biomarkers in general and in MG, and highlight important considerations for the analysis of circulating miRNA.

Keywords
myasthenia gravis, MG, microRNA, miR-150-5p, miR-21-5p, immunosuppressive, autoimmune disorders
National Category
Neurosciences Biochemistry and Molecular Biology Microbiology in the medical area
Research subject
Clinical Neurophysiology
Identifiers
urn:nbn:se:uu:diva-335288 (URN)10.1111/nyas.13510 (DOI)000423668100004 ()29125182 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048Swedish Cancer Society
Available from: 2017-12-03 Created: 2017-12-03 Last updated: 2018-05-08Bibliographically approved
Westerberg, E., Landtblom, A.-M. & Rostedt Punga, A. (2018). Lifestyle factors and disease-specific differences in subgroups of Swedish Myasthenia Gravis. Acta Neurologica Scandinavica, 138(6), 557-565
Open this publication in new window or tab >>Lifestyle factors and disease-specific differences in subgroups of Swedish Myasthenia Gravis
2018 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 6, p. 557-565Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To evaluate disease-specific differences between Myasthenia Gravis (MG) subgroups and compare patterns of lifestyle between MG patients and population controls.

METHODS: All MG patients (n=70) in Jönköping County, Sweden, were invited to answer a disease-specific questionnaire, containing questions about disease-specific data, lifestyle, co-morbidity and mental fatigue. The patients were clinically evaluated. Four hundred age- and gender matched population controls were invited to answer the non-disease-specific part of the questionnaire. Disease-specific issues were compared between MG subgroups. Lifestyle related factors and concomitant conditions were compared to the population controls.

RESULTS: Forty MG patients and 188 population controls participated in the study. In the late onset MG (LOMG; N=18) subgroup, the male predominance was higher than previously reported. In the early onset MG (EOMG; N=17) subgroup, time to diagnosis was longer, fatigue was higher and bulbar weakness was the dominant symptom (65%). Compared to their matched population controls, LOMG patients were more obese (OR 13.7, p=0.015), ate less fish (OR 4.1, p=0.012), tended to smoke more (OR 4.1, p=0.086) and tended to be employed as manual laborers more often (OR 2.82, p=0.083). Mental health problems and sickness benefits were more common among MG patients than in controls and MG patients were less regularly doing focused physical activity.

CONCLUSIONS: It is important to consider disease-specific differences when tailoring the management of individual MG patients. There is a need for improved knowledge on how to apply primary and secondary prevention measures to lifestyle disorders in MG patients without risk of deterioration.

Keywords
Early-onset MG, MG subgroups, Myasthenia Gravis, environmental factors, fatigue, late-onset MG, lifestyle
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-359968 (URN)10.1111/ane.13017 (DOI)000449696000012 ()30155967 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2018-09-07 Created: 2018-09-07 Last updated: 2019-06-27Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2178-9413

Search in DiVA

Show all publications