Autologous serum skin test reactions in chronic spontaneous urticaria differ from heterologous cell reactions

K. Baumann, J. Marcelino, P. S. Skov, M. C.P. Santos, I. Wyroslak, J. Scheffel, S. Altrichter, A. Woetmann, C. Costa, M. Maurer*

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Abstrakt

Background: Autoimmune chronic spontaneous urticaria (CSU) is due to mast cell (MC)-activating autoantibodies, which are screened for by the autologous serum skin test (ASST) and basophil tests (BTs). Many CSU patients are positive in only one of these tests. How often this occurs and why is currently unknown. Objectives: To characterize the prevalence of mismatched ASST and BTs in CSU patients, and to investigate possible reasons for these mismatches. Methods: We determined the rates of ASST+/BT− and ASST−/BT+ mismatches in published CSU studies. We assessed sera from 48 CSU patients by ASST, two BTs (basophil histamine release assay, BHRA; basophil activation test, BAT), a MC histamine release assay (MCHRA) and by ex vivo skin microdialysis (SMD). Results: The ASST/BT mismatch rate in published CSU studies was 31% (ASST+/BT−: 22%, ASST−/BT+: 9%). In our patients, the ASST/BHRA and ASST/BAT mismatch rate was 35.4% (ASST+/BHRA−: 18.8% and ASST−/BHRA+: 16.7%) and 31.3% (ASST+/BAT−: 6.3% and ASST−/BAT+: 25.0%), respectively, and the two BTs were significantly correlated (P = 0.0002). The use of heterologous MCs, in vitro and in situ, instead of basophils produced similar results (MCHRA mismatch: 47.9%, ASST+/MCHRA−: 18.8%, ASST−/MCHRA+: 29.2%; SMD mismatch: 40.0%, ASST+/SMD−: 10.0% and ASST−/SMD+: 30.0%), and the MCHRA was highly correlated with SMD results (P = 0.0002). Conclusions: The ASST and BTs show divergent results in a third of CSU patients. Mismatches cannot be explained by the choice of basophil assay, the type of heterologous cells exposed to CSU serum in vitro (basophils vs. mast cells), nor the experimental setting of heterologous skin mast cells (in vitro vs. in situ). Thus, serum-induced whealing, in CSU patients, seems to involve autologous skin signals modulating MC degranulation.

OriginalsprogEngelsk
TidsskriftJournal of The European Academy of Dermatology and Venereology
ISSN0926-9959
DOI
StatusE-pub ahead of print - 21. jan. 2021

Bibliografisk note

Funding Information:
Dr. Baumann has nothing to disclose. Dr. Marcelino has nothing to disclose. Dr. Skov has nothing to disclose. Dr. Pereira Santos has nothing to disclose. Dr. Wyroslak has nothing to disclose. Dr. Scheffel has nothing to disclose. Dr. Altrichter reports grants and personal fees from AstraZeneca, non‐financial support from Moxie, grants from Sanofi, grants from Novartis, grants and non‐financial support from Allakos, outside the submitted work. Dr. Woetmann has nothing to disclose. Dr. Costa has nothing to disclose. Dr. Maurer reports grants and personal fees from Allakos, personal fees from Aralez, grants from AstraZeneca, grants and personal fees from FAES, grants and personal fees from Genentech, grants and personal fees from Menarini, grants from LEO Pharma, grants and personal fees from Moxie, grants and personal fees from MSD, grants and personal fees from Roche, grants and personal fees from Sanofi, grants and personal fees from UCB, grants and personal fees from Uriach, grants and personal fees from Novartis, outside the submitted work.

Funding Information:
Intramural funding. Katrine Baumann was supported through an Industrial PhD Scholarship from Innovation Fund Denmark and a Research Fellowship from the European Academy of Allergy and Clinical Immunology (EAACI).

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