AUTHOR=Pérez-Díez Ainhoa , Liu Xiangdong , Calderon Stephanie , Bennett Ashlynn , Lisco Andrea , Kellog Anela , Galindo Frances , Memoli Matthew J. , Rocco Joseph M. , Epling Brian P. , Laidlaw Elizabeth , Sneller Mike C. , Manion Maura , Wortmann Glenn W. , Poon Rita , Kumar Princy , Sereti Irini 

TITLE=Prevalence of anti-lymphocyte IgM autoantibodies driving complement activation in COVID-19 patients

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1352330

DOI=10.3389/fimmu.2024.1352330

ISSN=1664-3224

ABSTRACT=COVID-19 patients can develop autoantibodies against a variety of secreted and membrane proteins, including some expressed on lymphocytes. It is unclear what proportion of patients might develop anti-lymphocyte antibodies (ALAb) and what their functional relevance may be. We evaluated the presence and lytic function of ALAb in a cohort of 85 COVID-19 patients (68 unvaccinated and 17 vaccinated) assigned into mild (N=63), or moderate/severe disease (N=22) groups. Thirty-seven patients were followed up after recovery. Compared to healthy donors (HD), patients had an increased prevalence of IgM ALAb, that was significantly higher in moderate/severe patients and persisted after recovery. Sera from IgM ALAb+ patients exhibited complement dependent cytotoxicity (CDC) against HD lymphocytes. Complement deposition on patients CD4 T cells inversely correlated with CD4 T cell numbers in moderate/severe patients. Thus, IgM ALAb and complement activation against lymphocytes may be contributing to the acute lymphopenia observed in COVID-19.