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=15 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=Introduction

COVID-19 patients can develop autoantibodies against a variety of secreted and membrane proteins, including some expressed on lymphocytes. However, it is unclear what proportion of patients might develop anti-lymphocyte antibodies (ALAb) and what functional relevance they might have.

Methods

We evaluated the presence and lytic function of ALAb in the sera of a cohort of 85 COVID-19 patients (68 unvaccinated and 17 vaccinated) assigned to mild (N=63), or moderate/severe disease (N=22) groups. Thirty-seven patients were followed-up after recovery. We also analyzed in vivo complement deposition on COVID-19 patients’ lymphocytes and examined its correlation with lymphocyte numbers during acute disease.

Results

Compared with healthy donors (HD), patients had an increased prevalence of IgM ALAb, which was significantly higher in moderate/severe disease patients and persisted after recovery. Sera from IgM ALAb+ patients exhibited complement-dependent cytotoxicity (CDC) against HD lymphocytes. Complement protein C3b deposition on patients’ CD4 T cells was inversely correlated with CD4 T cell numbers. This correlation was stronger in moderate/severe disease patients.

Discussion

IgM ALAb and complement activation against lymphocytes may contribute to the acute lymphopenia observed in COVID-19 patients.