Effective Anti–SARS-CoV-2 Immune Response in Patients With Clonal Mast Cell Disorders

Julien Rossignol (1, 2) , Amani Ouedrani (3, 4) , Cristina Bulai Livideanu (5) , Stéphane Barete (6) , Louis Terriou (7) , David Launay , Richard Lemal , Celine Greco , Laurent Frenzel , Cecile Meni , Christine Bodemere-Skandalis , Laura Polivka , Anne-Florence Collange , Hassiba Hachichi , Sonia Bouzourine , Djazira Nait Messaoud , Mathilde Negretto , Laurence Vendrame , Marguerite Jambou , Marie Gousseff , Stéphane Durupt , Jean-Christophe Lega , Jean-Marc Durand , Caroline Gaudy , Gandhi Damaj , Marie-Pierre Gourin , Mohamed Hamidou , Laurence Bouillet , Edwige Le Mouel , Alexandre Maria , Patricia Zunic , Quentin Cabrera , Denis Vincent , Christian Lavigne , Etienne Riviere , Clement Gourguechon , Marie Courbebaisse , David Lebeaux , Béatrice Parfait , Gérard Friedlander , Anne Brignier , Ludovic Lhermitte , Thierry Jo Molina , Julie Bruneau , Julie Agopian , Patrice Dubreuil , Dana Ranta , Alexandre Mania , Michel Arock , Isabelle Staropoli , Olivier Tournilhac (8) , Olivier Lortholary (1, 2) , Olivier Schwartz (9) , Lucienne Chatenoud (3, 4) , Olivier Hermine (1, 2)

1 CEREMAST - Centre de référence des mastocytoses
2 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
3 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
4 CHU Necker - Enfants Malades [AP-HP]
5 CEREMAST - Centre de Référence des Mastocytoses de Toulouse
6 CHU Pitié-Salpêtrière [AP-HP]
7 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
8 CHELTER - Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias
9 CNRS-UMR3569 - Virus et Immunité - Virus and immunity

Background Mast cells are key players in innate immunity and the TH2 adaptive immune response. The latter counterbalances the TH1 response, which is critical for antiviral immunity. Clonal mast cell activation disorders (cMCADs, such as mastocytosis and clonal mast cell activation syndrome) are characterized by abnormal mast cell accumulation and/or activation. No data on the antiviral immune response in patients with MCADs have been published. Objective To study a comprehensive range of outcomes in patients with cMCAD with PCR- or serologically confirmed coronavirus disease 2019 and to characterize the specific anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response in this setting. Methods Clinical follow-up and outcome data were collected prospectively over a 12-month period by members of the French Centre de Référence des Mastocytoses rare disease network. Anti–SARS-CoV-2–specific T-cell activity was measured with an ELISA, and humoral responses were evaluated by assaying circulating levels of specific IgG, IgA, and neutralizing antibodies. Results Overall, 32 patients with cMCAD were evaluated. None required noninvasive or mechanical ventilation. Two patients were admitted to hospital for oxygen and steroid therapy. The SARS-CoV-2–specific immune response was characterized in 21 of the 32 patients. Most had high counts of circulating SARS-CoV-2–specific, IFN-γ–producing T cells and high titers of neutralizing antispike IgGs. The patients frequently showed spontaneous T-cell IFN-γ production in the absence of stimulation; this production was correlated with basal circulating tryptase levels (a marker of the mast cell burden). Conclusions Patients with cMCADs might not be at risk of severe coronavirus disease 2019, perhaps due to their spontaneous production of IFN-γ.

Keywords: SARS-CoV-2; COVID-19; Mast cells; Mastocytosis; Clonal mast cell activation syndrome; Mast cell activation dis- orders; T cells; B cells

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Virology

Julien Rossignol, Amani Ouedrani, Cristina Bulai Livideanu, Stéphane Barete, Louis Terriou, et al.. Effective Anti–SARS-CoV-2 Immune Response in Patients With Clonal Mast Cell Disorders. The Journal of Allergy and Clinical Immunology: In Practice, 2022, 10 (5), pp.1356-1364.e2. ⟨10.1016/j.jaip.2021.12.038⟩. ⟨pasteur-03697054⟩