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Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). It develops approximately 4 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS-C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS-C, diagnosis, treatment, follow-up, and the role of COVID-19 vaccinations. MIS-C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short-term outcome, MIS-C patients should be followed-up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID-19 vaccination is a safe and effective measure to prevent MIS-C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS-C developed by the Immunology Section of the EAACI.

Additional file 1: Table S1. Systematic search strategy. Table S2. Systematic search on IgE autoantibodies in patients with atopic dermatitis. AD: atopic dermatitis, RC: rhino conjunctivitis, NA: nonatopic, HC: healthy controls without allergic symptoms, PS: psoriasis, CA: contact allergy, UA: urticaria. Table S3. Autoreactive T cells in patients with atopic dermatitis. AD: atopic dermatitis, RC: rhinoconjunctivitis, HC: healthy controls, NA: non-atopic, CD: chronic dermatoses, PS: psoriasis, ns: non-sensitized, ABPA: allergic bronchopulmonary aspergillosis. * median.

BACKGROUND: Desensitization is a method for inducing temporary tolerance to allergen. The mechanism underlying desensitization is yet to be established.METHODS: Basophil granulocytes in whole blood from grass pollen allergic subjects were desensitized ex vivo by sequential addition of increasing allergen concentrations. At each step basophil activation (CD193(+) CD63(+) ) was monitored with and without (background activation) allergen challenge at optimal concentration. The sequential desensitization protocol was compared to a single-dose desensitization protocols with threshold and subthreshold allergen concentrations. Incubation intervals and allergen concentrations were varied in order to optimise the protocol.RESULTS: Sequential desensitization effectively reduced basophil response. The single-dose subthreshold protocol and single-dose threshold protocols did not reduce basophil activation with optimal allergen challenge from a mean 57.1 (95% CI 32.7-81.5) to 50.4% (95% CI 16.3-84.4; n=5; p=0.43) and 45.0% (95% CI 23.1-66.9; p=0.14) respectively, while the sequential desensitization protocol reduced activation to a mean 37.2% (95% CI 16.3-58.1; p=0.018). Reducing incubation time from 10 to 5 minutes increased mean background activation from 22.4 (95% CI 11.7-33.1) to 30.0% (95% CI 19.7-40.3; n=5; p=0.026). Increasing time intervals from 10 to 20 minutes reduced background activation from 30.9 (95% CI 22.8-39.0) to 21.9% (95% CI 16.0-27.7; n=5; p=0.020). Increasing allergen concentrations intervals from 2-fold to 5- and 10-fold did not have significant effect on basophil activation.CONCLUSIONS: Sequential desensitization ex vivo effectively attenuates the basophil response to allergen. Increasing the time spent at each step improves desensitization. This protocol could be valuable for investigation of the mechanism of desensitization. This article is protected by copyright. All rights reserved.