Nicole Schoepke1, Riccardo Asero2, André Ellrich1, Marta Ferrer3, Ana Gimenez-Arnau4, Clive E H Grattan5, Thilo Jakob6,7, George N Konstantinou8, Ulrike Raap9, Per Stahl Skov10,11, Petra Staubach12, Arno Kromminga13,14, Ke Zhang15, Carsten Bindslev-Jensen16, Alvaro Daschner17, Tamar Kinaciyan18, Edward F Knol19, Michael Makris20, Nadine Marrouche21, Peter Schmid-Grendelmeier22,23, Gordon Sussman24, Elias Toubi25, Martin K Church1, Marcus Maurer1. 1. Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany. 2. Department of Allergology, Clinica San Carlo, Paderno Dugnano (MI), Italy. 3. Department of Allergy and Clinical Immunology, Clinica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), RETIC de Asma, Reacciones adversas y Alérgicas (ARADYAL), Pamplona, Spain. 4. Department of Dermatology, Hospital del Mar, IMIM, Universitat Autònoma Barcelona, Barcelona, Spain. 5. Guy's Hospital, London, UK. 6. Department of Dermatology and Allergology, University Medical Center Giessen and Marburg, Justus-Liebig University Gießen, Gießen, Germany. 7. Allergy Research Group, Medical Center, University of Freiburg, Freiburg, Germany. 8. Department of Allergy and Clinical Immunology, 424 General Military Training Hospital, Thessaloniki, Greece. 9. Department of Human Medicine and Health Sciences, University Clinic of Dermatology and Allergy, University of Oldenburg, Oldenburg, Germany. 10. RefLab ApS, Copenhagen, Denmark. 11. Odense Research Center of Anaphylaxis, ORCA, Odense, Denmark. 12. Department of Dermatology, University Medical Center Mainz, Mainz, Germany. 13. Bioagilytix Europe GmbH, Hamburg, Germany. 14. Institute of Immunology, University of Kiel, Kiel, Germany. 15. Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. 16. Department of Dermatology and Allergy Centre, Odense University Hospital, University of Southern Denmark, Odense, Denmark. 17. Servicio de Alergia, Instituto de Investigación Sanitaria (IIS)- Hospital Universitario de la Princesa, Madrid, Spain. 18. Department of Dermatology, Medical University of Vienna, Vienna, Austria. 19. Departments of Immunology and Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands. 20. Allergy Unit, 2nd Department of Dermatology and Venereology, Medical School, National and Kapodistrian University of Athens, Attikon" University Hospital, Athens, Greece. 21. Department of Dermatology, Norfolk and Norwich University Hospital, Norwich, UK. 22. Allergy Unit, Department of Dermatology, University Hospital, Zürich, Switzerland. 23. Christine Kühne Center for Allergy Research and Education CK-CARE, Davos, Switzerland. 24. Division of Allergy and Clinical Immunology, University of Toronto, Toronto, Ontario, Canada. 25. Faculty of Medicine, Bnai-Zion Medical Center, Technion, Haifa, Israel.
Abstract
BACKGROUND: Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high-affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU. METHODS: This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti-FcεRI and IgG anti-IgE; IgG-anti-thyroperoxidase (IgG anti-TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA). RESULTS: Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti-FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P < 0.016) but showed no other clinical or demographic differences from non-aiCSU patients. aiCSU patients also had markedly lower total IgE levels (P < 0.0001) and higher IgG anti-TPO levels (P < 0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively. CONCLUSIONS: aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management.
BACKGROUND:Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high-affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU. METHODS: This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti-FcεRI and IgG anti-IgE; IgG-anti-thyroperoxidase (IgG anti-TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA). RESULTS: Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti-FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P < 0.016) but showed no other clinical or demographic differences from non-aiCSU patients. aiCSU patients also had markedly lower total IgE levels (P < 0.0001) and higher IgG anti-TPO levels (P < 0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively. CONCLUSIONS: aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management.
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