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  • 1. Ebisawa, Motohiro
    et al.
    Moverare, Robert
    Sato, Sakura
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ito, Komei
    The predictive relationship between peanut- and Ara h 2-specific serum IgE concentrations and peanut allergy2015In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, ISSN 2213-2198, Vol. 3, no 1, p. 131-132.e1Article in journal (Refereed)
  • 2. Ebisawa, Motohiro
    et al.
    Movérare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Sato, Sakura
    Maruyama, Nobuyuki
    Borres, Magnus P.
    Komata, Takatsugu
    Measurement of Ara h 1-, 2-, and 3-specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children2012In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 23, no 6, p. 573-581Article in journal (Refereed)
    Abstract [en]

    Background: Food challenges are time-consuming, expensive, and not always possible to perform. Therefore, new tools to diagnose food allergy are desired. The aim was to evaluate IgE antibodies to peanut allergens in the diagnosis of peanut allergy in Japanese children using ImmunoCAP (R) and IgE immunoblotting.

    Methods: The study included 213-yr-old consecutive patients (n = 57) referred to our specialist clinic for investigation of current peanut allergy using food challenge. All children had a previous doctors diagnosis of peanut allergy and were on elimination diet. Serum samples were analyzed for IgE reactivity to peanut, recombinant (r) Ara h 1, 2, 3, 5, 8, and 9. IgE immunoblotting (n = 23) was performed using extracts from raw and roasted peanut.

    Results: Twenty-six of the children failed (allergic group), and 31 passed the peanut challenge (tolerant group). The rAra h 2 ImmunoCAP test was superior in its ability to differentiate between children in the allergic and tolerant groups with a sensitivity and specificity of 88% and 84%, respectively (cutoff, 0.35 kUA/l). The combination of rAra h 1, 2, and 3 resulted in a higher specificity (94%) when IgE to all of them was the criteria for positivity. ImmunoCAP generally showed a good agreement with immunoblotting using both raw and roasted peanut for IgE reactivity to Ara h 1, 2, and 3.

    Conclusions: Measurement of IgE antibodies to rAra h 1, 2, and 3 is useful in the diagnosis of peanut allergy and in the investigation of reactions to raw and roasted peanut.

  • 3. Englund, H.
    et al.
    Kuitunen, M.
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Borres, M. P.
    Makela, M.
    IgE and IgG(4) antibody levels towards milk components are associated with outcome of oral immunotherapy in Finnish milk allergic children2013In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no Suppl. s97, p. 327-327Article in journal (Other academic)
  • 4. Eriksson, C.
    et al.
    Lind, P.
    Nystrand, M.
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    A new automated anti-drug antibody screening assay with high sensitivity and drug tolerance2013In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no Suppl. s97, p. 142-142Article in journal (Other academic)
  • 5. Everberg, Henrik
    et al.
    Brostedt, Peter
    Öman, Hans
    Bohman, Svante
    Movérare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Affinity Purification of Egg-White Allergens for Improved Component-Resolved Diagnostics2011In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 154, no 1, p. 33-41Article in journal (Refereed)
    Abstract [en]

    Background: Egg is a common cause of food-allergic reactions, especially among young children. Some egg-allergic patients do, however, tolerate heated egg products and component-resolved diagnostics (CRD) may facilitate prediction of different disease manifestations. Commercially available preparations of the egg-white allergens, ovomucoid, ovalbumin, conalbumin and lysozyme, have been reported to contain impurities which interfere with accurate CRD. Methods: Commercial preparations of the 4 egg-white allergens were characterized using allergen-specific monoclonal chimeric human/mouse IgE antibodies in experimental ImmunoCAP (R) tests. Further purification of commercial ovomucoid, ovalbumin and conalbumin preparations was performed by chromatography based on affinity to monoclonal antibodies. Purity was monitored by size exclusion chromatography, SDS-PAGE, Western blotting and experimental ImmunoCAP tests using allergen-specific chimeric IgE antibodies. IgE reactivity to the highly purified egg components was analyzed in 83 samples from egg white-sensitized individuals. Results: Preparations of commercially available ovomucoid, ovalbumin and conalbumin were found to contain other egg allergens which were removed by chromatographic purification. No impurities were detected in the commercial lysozyme preparation. Previously unknown complexes between the target allergens and contaminating allergens were detected and removed by affinity chromatography. IgE reactivity to ovalbumin was most common in the analyzed samples (87%), followed by ovomucoid (72%), conalbumin (69%) and lysozyme (58%). Conclusions: In this study we demonstrate the advantage of using monoclonal antibodies for purification, and monoclonal chimeric IgE antibodies for characterization, of egg allergens intended for CRD. Our study also established that ovalbumin, ovomucoid, conalbumin and lysozyme are all major allergens.

  • 6. Glaumann, S.
    et al.
    Nilsson, C.
    Asarnoj, A.
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Johansson, S. G. O.
    Borres, M. P.
    Lilja, G.
    Nopp, A.
    IgG(4) antibodies and peanut challenge outcome in children IgE-sensitized to peanut2015In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 26, no 4, p. 386-389Article in journal (Refereed)
  • 7. Ito, Komei
    et al.
    Futamura, Masaki
    Movérare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Tanaka, Akira
    Kawabe, Tsutomu
    Sakamoto, Tatsuo
    Borres, Magnus P
    The usefulness of casein-specific IgE and IgG4 antibodies in cow's milk allergic children2012In: Clinical and Molecular Allergy, ISSN 1476-7961, E-ISSN 1476-7961, Vol. 10, no 1, p. 1-Article in journal (Refereed)
    Abstract [en]

    Background

    Cow's milk allergy is one of the most common food allergies among younger children. We investigated IgE antibodies to milk, and IgE and IgG4 antibodies to casein, α-lactalbumin and β-lactoglobulin in cow's milk allergic (CMA) and non-allergic (non-CMA) children in order to study their clinical usefulness.

    Methods

    Eighty-three children with suspected milk allergy (median age: 3.5 years, range: 0.8-15.8 years) were diagnosed as CMA (n = 61) or non-CMA (n = 22) based on an open milk challenge or convincing clinical history. Their serum concentrations of allergen-specific (s) IgE and IgG4 antibodies were measured using ImmunoCAP®. For the sIgG4 analysis, 28 atopic and 31 non-atopic control children were additionally included (all non-milk sensitized).

    Results

    The CMA group had significantly higher levels of milk-, casein- and β-lactoglobulin-sIgE antibodies as compared to the non-CMA group. The casein test showed the best discriminating performance with a clinical decision point of 6.6 kUA/L corresponding to 100% specificity. All but one of the CMA children aged > 5 years had casein-sIgE levels > 6.6 kUA/L. The non-CMA group had significantly higher sIgG4 levels against all three milk allergens compared to the CMA group. This was most pronounced for casein-sIgG4 in non-CMA children without history of previous milk allergy. These children had significantly higher casein-sIgG4 levels compared to any other group, including the non-milk sensitized control children.

    Conclusions

    High levels of casein-sIgE antibodies are strongly associated with milk allergy in children and might be associated with prolonged allergy. Elevated casein-sIgG4 levels in milk-sensitized individuals on normal diet indicate a modified Th2 response. However, the protective role of IgG4 antibodies in milk allergy is unclear.

  • 8. Ito, Komei
    et al.
    Sjölander, Sigrid
    Sato, Sakura
    Movérare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Tanaka, Akira
    Soderstrom, Lars
    Borres, Magnus
    Poorafshar, Maryam
    Ebisawa, Motohiro
    IgE to Gly m 5 and Gly m 6 is associated with severe allergic reactions to soybean in Japanese children2011In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 128, no 3, p. 673-675Article in journal (Refereed)
  • 9. Kuitunen, M.
    et al.
    Englund, H.
    Remes, S.
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Pelkonen, A.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Makela, M. J.
    High IgE levels to -lactalbumin, -lactoglobulin and casein predict less successful cow's milk oral immunotherapy2015In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 70, no 8, p. 955-962Article in journal (Refereed)
    Abstract [en]

    BackgroundA new treatment option for persistent cow's milk allergy (CMA) is oral immunotherapy (OIT). Not all patients develop tolerance during therapy, and markers to identify those who will benefit from it are needed. The objective was to study the IgE and IgG(4) antibody profiles to milk and milk proteins before and after OIT in relation to clinical outcome. MethodsSeventy-six children (5-17years) with challenge-verified CMA were subjected to a 6-month OIT protocol. The treatment aimed at reaching a maintenance dose of 200ml CM (high dose=HD). Those who did not reach target were analysed as a low-dose (LD) group. Sera were characterized before and after OIT regarding serum levels of IgE and IgG(4) to milk and five milk allergen components evaluated together with clinical CMA symptoms and outcome of OIT. ResultsFifty-five (72%) patients reached the maintenance dose (HD) during therapy. High specific IgE levels towards the milk allergens -lactalbumin (P=0.048), -lactoglobulin (P=0.006) and casein (P=0.015) before OIT start were associated with lower maintenance dose reached. Patients who developed desensitization had a larger increase in IgG(4) levels to -lactalbumin (P=0.034), -lactoglobulin (P=0.010), casein (P=0.047) and lactoferrin (P=0.030) during treatment than those who failed. ConclusionsComponent-resolved diagnostics before OIT can help to identify children with lower probability of a successful OIT outcome, as high IgE levels to -lactalbumin, -lactoglobulin and casein are associated with lower maintenance dose reached. An increase in the IgG(4) concentration to milk components during treatment indicated effective desensitization.

  • 10. Lundkvist, M.
    et al.
    Engdahl, E.
    Holmen, C.
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Olsson, T.
    Hillert, J.
    Fogdell-Hahn, A.
    Characterization of anti-natalizumab antibodies in multiple sclerosis patients2013In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 6, p. 757-764Article in journal (Refereed)
    Abstract [en]

    Background: A small proportion of multiple sclerosis (MS) patients treated with natalizumab develop anti-drug antibodies. Objective: The objective of this paper is to characterize the anti-natalizumab antibody response and to investigate differences between persistently and transiently antibody-positive patients. Methods: Screening for anti-natalizumab antibodies was performed using a standardized bridging ELISA. Antibody-positive samples were further analyzed for IgM and IgG1-4 antibodies using ELISA and ImmunoCAP (R). Results: Anti-natalizumab antibodies developed in 57 of 1379 (4.1%) treated patients after a median treatment duration of three months. Of the positive patients, 20 (35%) patients reverted to negative, 19 (33%) patients were confirmed persistently positive and 18 (32%) patients were unconfirmed positive. Significantly higher anti-natalizumab antibody levels were detected in persistently compared to transiently positive patients. A cutoff value predicting persistence of antibodies could be determined with a sensitivity of 0.84 and a specificity of 0.80. IgM and IgG4 antibody levels were significantly higher in persistently compared to transiently positive patients, and IgG1, IgG2 and IgG4 increased significantly over time. Conclusions: The level of total anti-natalizumab antibodies in a first positive sample can be used to predict patients at risk for persisting antibody positivity. However, neither IgM nor IgG1-4 antibodies could be used to discriminate between transiently and persistently positive patients.

  • 11. Lundkvist, Malin
    et al.
    Engdahl, Elin
    Holmen, Carolina
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Olsson, Tomas
    Hillert, Jan
    Fogdell-Hahn, Anna
    Anti-Natalizumab Antibodies in Patients with Multiple Sclerosis2012In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 76, no 2, p. 206-207Article in journal (Other academic)
  • 12.
    Maruyama, N.
    et al.
    Kyoto Univ, Grad Sch Agr, Lab Food Qual Design & Dev, Uji, Kyoto 6110011, Japan..
    Nakagawa, T.
    Aichi Childrens Hlth & Med Ctr, Dept Allergy, Obu, Aichi, Japan..
    Ito, K.
    Aichi Childrens Hlth & Med Ctr, Dept Allergy, Obu, Aichi, Japan..
    Cabanos, C.
    Kyoto Univ, Grad Sch Agr, Lab Food Qual Design & Dev, Uji, Kyoto 6110011, Japan..
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Thermo Fisher Sci, Uppsala, Sweden..
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Thermo Fisher Sci, Uppsala, Sweden..
    Tanaka, A.
    Thermo Fisher Sci, Tokyo, Japan..
    Sato, S.
    Sagamihara Natl Hosp, Clin Res Ctr Allergol & Rheumatol, Dept Allergy, Sagamihara, Kanagawa, Japan..
    Ebisawa, M.
    Sagamihara Natl Hosp, Clin Res Ctr Allergol & Rheumatol, Dept Allergy, Sagamihara, Kanagawa, Japan..
    Measurement of specific IgE antibodies to Ses i 1 improves the diagnosis of sesame allergy2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 1, p. 163-171Article in journal (Refereed)
    Abstract [en]

    Background The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis. Objective The aim was to identify the allergen components useful to diagnose sesame-allergic children with the goal to reduce the number of OFCs needed. Methods Ninety-two sesame-sensitized children were consecutively enrolled and diagnosed based on OFC or convincing history. Specific IgE to purified native 11S globulin (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S), and two recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or ImmunoCAP (rSes i 1/streptavidin application). Results Based on area under curve (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was shown to have the best diagnostic performance of the allergen components in ELISA. The experimental rSes i 1 ImmunoCAP test had larger AUC (0.891; 95% CI, 0.826-0.955) compared to the commercially available sesame ImmunoCAP (0.697; 95% CI, 0.589-0.805). The clinical sensitivity and specificity for the rSes i 1 ImmunoCAP test at optimal cut-off (3.96 kUA/L) were 86.1% and 85.7%, respectively. Conclusion and Clinical Relevance Sensitization to Ses i 1 is strongly associated with clinical sesame allergy. Measurement of specific IgE to rSes i 1 could reduce the numbers of OFCs needed.

  • 13.
    Maruyama, Nobuyuki
    et al.
    Kyoto Univ, Grad Sch Agr, Lab Food Qual Design & Dev, Kyoto 6110011, Japan..
    Sato, Sakura
    Sagamihara Natl Hosp, Clin Res Ctr Allergol & Rheumatol, Sagamihara, Kanagawa, Japan..
    Yanagida, Noriyuki
    Sagamihara Natl Hosp, Dept Pediat, Sagamihara, Kanagawa, Japan..
    Cabanos, Cerrone
    Kyoto Univ, Grad Sch Agr, Lab Food Qual Design & Dev, Kyoto 6110011, Japan..
    Ito, Komei
    Aichi Childrens Hlth & Med Ctr, Dept Allergy, Obu, Japan..
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Thermo Fisher Sci, Uppsala, Sweden..
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Thermo Fisher Sci, Uppsala, Sweden..
    Tanaka, Akira
    Thermo Fisher Sci, Tokyo, Japan..
    Ebisawa, Motohiro
    Sagamihara Natl Hosp, Clin Res Ctr Allergol & Rheumatol, Sagamihara, Kanagawa, Japan..
    Clinical utility of recombinant allergen components in diagnosing buckwheat allergy2016In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, ISSN 2213-2198, Vol. 4, no 2, p. 322-+Article in journal (Refereed)
  • 14.
    Moverare, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Ahlstedt, Staffan
    Bengtsson, Ulf
    Borres, Magnus P.
    van Hage, Marianne
    Poorafshar, Maryam
    Sjolander, Sigrid
    Akerstrom, Johanna
    van Odijk, Jenny
    Evaluation of IgE Antibodies to Recombinant Peanut Allergens in Patients with Reported Reactions to Peanut2011In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 156, no 3, p. 282-290Article in journal (Refereed)
    Abstract [en]

    Background: Peanut may cause severe reactions in allergic individuals. The objective was to evaluate IgE antibodies to various recombinant (r) peanut and birch pollen allergens in relation to IgE levels to whole peanut extract and severe allergic reactions to peanut. Methods: Seventy-four Swedish peanut-allergic patients (age: 14-61 years) reported previous peanut exposure and associated symptoms using a questionnaire. Their IgE reactivity to peanut, birch pollen and individual allergen components was analyzed using ImmunoCAP(R). Results: Of the 48 subjects sensitized to Ara h 1, 2 or 3, 60% had peanut-specific IgE levels >15 kU(A)/l, while 100% of the subjects without detectable IgE to these allergens had low peanut-specific IgE levels (<10 kU(A)/l). The levels of IgE to rAra h 8, rBet v 1 and birch pollen were highly correlated (r(S) = 0.94, p < 0.0001). Fifty-eight patients reported adverse reactions after accidental or deliberate peanut exposure (oral, inhalation or skin) of whom 41 had IgE to rAra h 1, 2 or 3. Symptoms of respiratory distress were associated with sensitization to Ara h 1, 2 or 3 (56 vs. 18%, p < 0.01). Two cases of anaphylaxis were reported among the individuals sensitized to Ara h 1-3. IgE to rAra h 8, rAra h 9, profilin or cross-reactive carbohydrate determinants were not associated with severe symptoms. Conclusions: The results indicate that IgE reactivity to Ara h 1, 2 and 3 is associated with severe reactions after exposure to peanut in Swedish patients.

  • 15.
    Movérare, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Thermo Fisher Sci, ImmunoDiagnost, Uppsala, Sweden.
    Blume, Karin
    Thermo Fisher Sci, ImmunoDiagnost, Uppsala, Sweden..
    Lind, Peter
    Thermo Fisher Sci, ImmunoDiagnost, Uppsala, Sweden..
    Crevel, Rene
    Unilever SEAC, Colworth Sci Pk, Sharnbrook, Beds, England..
    DeWitt, Asa Marknell
    Thermo Fisher Sci, ImmunoDiagnost, Uppsala, Sweden..
    Cochrane, Stella
    Unilever SEAC, Colworth Sci Pk, Sharnbrook, Beds, England..
    Measurement of human IgG subclass antibodies to allergens with new research ImmunoCAP assays2017In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 306-306Article in journal (Other academic)
  • 16.
    Movérare, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Thermo Fisher Sci, ImmunoDiagnost, POB 6460, SE-75137 Uppsala, Sweden..
    Blume, Karin
    Thermo Fisher Sci, ImmunoDiagnost, POB 6460, SE-75137 Uppsala, Sweden..
    Lind, Peter
    Thermo Fisher Sci, ImmunoDiagnost, POB 6460, SE-75137 Uppsala, Sweden..
    Crevel, Rene
    Unilever SEAC, Colworth Sci Pk, Sharnbrook, Beds, England..
    DeWitt, Åsa Marknell
    Thermo Fisher Sci, ImmunoDiagnost, POB 6460, SE-75137 Uppsala, Sweden..
    Cochrane, Stella
    Unilever SEAC, Colworth Sci Pk, Sharnbrook, Beds, England..
    Human Allergen-Specific IgG Subclass Antibodies Measured Using ImmunoCAP Technology2017In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 172, no 1, p. 1-10Article in journal (Refereed)
    Abstract [en]

    Background: Knowledge of human IgG subclass antibody responses to various allergens has been hampered by a lack of reliable standardized assays. The aim here was to develop quantitative immunoassays for human IgG1, IgG2, and IgG3 antibodies using ImmunoCAP (R) technology and to evaluate their application. Methods: Enzyme conjugates with isotype-specific monoclonal antibodies and calibrators composed of purified myeloma paraproteins were developed for each assay and used together with other standardized assay reagents for the Phadia (R) 100 instrument. The calibrators were adjusted to the international reference preparation IRP 67/86. The assays were characterized and used together with other standard ImmunoCAP assays to measure antibodies to various allergens in preliminary studies. Results: The new assays had limits of quantitation of 1.0 (IgG1), 4.6 (IgG2), and 0.04 mg(A)/L (IgG3), and coefficients of variation of <20%. Only some minor cross -reactivity with IgG2 was observed for the specific IgG1 assay. The specific IgG2 assay showed a bias for the allotype G2m(23) and compensation factors were used to adjust the measured concentrations accordingly. Preliminary studies indicated a strong and stable IgG4 antibody response to P-lactoglobulin in healthy individuals, a high IgG1 and even higher IgG2 antibody response to house dust mite in sensitized and nonsensitized subjects, and a mixed IgG subclass response to venom allergens in allergic patients with increasing IgG4 antibody levels during venom immunotherapy. Conclusions: The new research assays are valuable tools for immunological studies, enabling the characterization of antibody profiles using a standardized approach, and facilitating data interpretation and the comparison of results across studies.

  • 17.
    Movérare, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Kosunen, T. U.
    Haahtela, T.
    Change in the pattern of IgE reactivity to timothy grass and birch pollen allergens over a 20-year period2006In: Journal of investigational allergology & clinical immunology, ISSN 1018-9068, E-ISSN 1698-0808, Vol. 16, no 5, p. 274-278Article in journal (Refereed)
    Abstract [en]

    Background: Several studies have shown that the prevalence of allergy and allergen sensitization has increased in recent years. However, the changes in the pattern of IgE reactivity to individual allergens are mostly unknown.

    Objective: The aim of this preliminary study was. to assess the change in IgE reactivity profile to individual timothy grass and/or birch pollen allergens in sera from sensitized individuals randomly collected 20 years apart.

    Methods: Serum samples from 51 sensitized individuals were obtained from 2 cross-sectional surveys performed in 1973 and 1994 using random samples from Vammala, Finland. The sera were analyzed for IgE reactivity to timothy grass and/or birch pollen extracts, recombinant (r)Phl p 1, 2, 5, 6, 7, 11, 12, native (n)Phl p 4, and rBet v 1, 2 and 4 by immunoassay (ImmunoCAP).

    Results: The median (range) concentrations of IgE antibodies to timothy grass and birch pollen were higher in 1994 than in 1973 (6.47 [0.35 to > 100] kU(A)/L vs 1.53 [0.40-25.3] kU(A)[L; P=.0035). The prevalence of IgE reactivity to some allergens was higher in 1994 than in 1973, particularly rPhl p 5 (52% vs 19%), rPhl p 6 (43% vs 12%), and rBet v 1 (100% vs 29%). There was a correlation between timothy grass pollen-specific serum IgE levels and the numbers of IgE reactivities to individual allergens (p=0.76, P <.001).

    Conclusions: The increase in specific IgE levels together with a possible increase in the prevalence of IgE reactivity to the major allergens Phl p 5 and Bet v 1 between 1973 and 1994 may have contributed to the increase in atopic conditions in Finland.

  • 18.
    Movérare, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Larsson, Håkan
    Carlsson, Raimo
    Holmquist, Ingrid
    Mugwort-Sensitized Individuals from North Europe, South Europe and North America Show Different IgE Reactivity Patterns2011In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 154, no 2, p. 164-172Article in journal (Refereed)
    Abstract [en]

    Background: Sensitization to weed pollen allergens at the molecular level is not fully understood. We studied IgE reactivity to the major mugwort allergen Art v 1 in relation to allergens from other weed pollen and cross-reactive components in mugwort-sensitized subjects. Methods: Art v 1 and Amb a 1 were affinity purified and coupled to experimental ImmunoCAP (R) tests. Samples from North Europe (n = 50), South Europe (n = 19) and North America (n = 41) were analyzed for IgE against mugwort pollen, weed allergen components, pan-allergens and cross-reactive carbohydrate determinants (CCDs). Results: The prevalence of IgE reactivity (> 0.35 kU(A)/l) to Art v 1 was significantly higher in samples from North Europe than in those from North America. IgE to Amb a 1 was more common in North America than in North and South Europe, while IgE to Par j 2 was common in South Europe, less common in North America, and absent in North Europe. IgE to Art v 3 in mugwort-allergic patients was more common in North Europe than in South Europe and North America, while IgE to Sal k 1 was similar between the areas. Subjects with an Art v 1/mugwort-specific IgE ratio < 0.5 had more often IgE to Amb a 1, profilin, polcalcin and CCDs than subjects with a ratio > 0.5. Conclusions: Mugwort-sensitized subjects have different IgE reactivity profiles to weed allergens, reflecting their exposure to various pollens. Subjects with a low ratio between the IgE levels to Art v 1 and mugwort have a diverse IgE reactivity profile, indicating a role for cross-reactive allergens in their mugwort sensitization.

  • 19. Nozawa, Asako
    et al.
    Okamoto, Yoshihisa
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kurihara, Kazuyunki
    Monitoring Ara h 1, 2 and 3-sIgE and sIgG4 antibodies in peanut allergic children receiving oral rush immunotherapy2014In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, no 4, p. 323-328Article in journal (Refereed)
    Abstract [en]

    Background: The aim was to study the clinical efficacy and safety of rush oral immunotherapy (OIT) for severe peanut-allergic children and to measure the antibody responses. Methods: Eighteen Japanese children were enrolled after a positive double-blind, placebo-controlled food challenge (DBPCFC). The patients ingested peanuts up to 3-5 times a day every 30 min, increasing the dose by 20% every time. The goal dose was 3.5-7 g. IgE, IgG, and IgG4 antibody levels to peanut, and peanut allergen components were measured during up to 3 yr of maintenance treatment. Results: Two children dropped out due to side effects. Sixteen patients (14 boys and two girls, median: 9 yr range: 5-14 yr) achieved the goal dose after a median of 11 days (range: 4-19 days). Their median threshold dose at DBPCFC was 0.20 g (range: 0.015-1.0 g). All were sensitized to Ara h 2. Fourteen of them had a history of previous anaphylaxis. In total, 173 adverse events were observed during the treatment (27% of the total ingestions) of which 74 needed medications. The median IgE, IgG, and IgG4 antibody levels to peanut increased during rush OIT. The IgG4 levels were high during the whole maintenance phase. IgE and IgG4 antibodies to Ara h 2 dominated the serological response during the treatment. Conclusions: The present rush OIT protocol for children with severe peanut allergy was effective and relatively safe. A sustained Ara h 2-specific IgG4 antibody response characterized the treatment.

  • 20. Sato, Sakura
    et al.
    Yamamoto, Mikita
    Yanagida, Noriyuki
    Ito, Komei
    Ohya, Yukihiro
    Imai, Takanori
    Nagao, Mizuho
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Thermo Fisher Sci.
    Movérare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Thermo Fisher Sci.
    Ebisawa, Motohiro
    Jug r 1 sensitization is important in walnut-allergic children and youth.2017In: Journal of Allergy and Clinical Immunology: In Practice, ISSN 2213-2198, E-ISSN 2213-2201, Vol. 5, no 6, p. 1784-1786.e1Article in journal (Other academic)
  • 21. Wedbäck, Anna
    et al.
    Enbom, Håkan
    Eriksson, Nils E.
    Moverare, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Malcus, Inga
    Seasonal non-allergic rhinitis (SNAR)--a new disease entity?: A clinical and immunological comparison between SNAR, seasonal allergic rhinitis and persistent non-allergic rhinitis2005In: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 43, no 2, p. 86-92Article in journal (Refereed)
    Abstract [en]

    We have earlier described a group of patients suffering from rhino-conjunctivitis during the early pollen season, but with negative allergological investigation. The present study aimed to evaluate this syndrome called Seasonal Non-Allergic Rhinitis (SNAR). Seventeen patients with SNAR were compared with 20 patients with seasonal allergic rhinitis (SAR) and 13 patients with persistent non-allergic rhinitis (PNAR). They were analyzed with skin prick tests (SPT) and nasal provocation tests (NPT) with pollen extracts, and for IgE antibodies in serum and inflammation mediators in nasal lavage. Daily symptoms and medicine consumption were recorded. Late reactions after SPT occurred in two SNAR, eight SAR and two PNAR patients. Weak immediate and late reactions after NPT were induced in 3/15 and 7/15 SNAR patients, respectively, and in 1/13 and 5/13 PNAR patients. All SAR patients had immediate and 9/18 had late reactions. The total IgE levels were lower in SNAR compared to SAR. In the SNAR group 1/15 was positive in Phadiatop. Increased tryptase levels after NPT were only observed in SAR. The SNAR patients had high daily symptom scores already before birch pollen season. Sneezing was more common in SNAR and SAR than in PNAR; eye-symptoms more prominent in SAR than in SNAR or PNAR. SNAR seems to be different from SAR and PNAR regarding immunological mechanism and symptom period. We conclude that the cause of SNAR is unknown

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