Prevalence of anti-lymphocyte IgM autoantibodies driving complement activation in COVID-19 patients.
- 2024
Discussion: IgM ALAb and complement activation against lymphocytes may contribute to the acute lymphopenia observed in COVID-19 patients. Copyright © 2024 Perez-Diez, Liu, Calderon, Bennett, Lisco, Kellog, Galindo, Memoli, Rocco, Epling, Laidlaw, Sneller, Manion, Wortmann, Poon, Kumar and Sereti. 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.
English
1664-3224
PMC11061367 [pmc]
*Autoantibodies
*Complement Activation
*COVID-19
*Immunoglobulin M
*SARS-CoV-2
Adult
Aged
Autoantibodies/bl [Blood]
Autoantibodies/im [Immunology]
CD4-Positive T-Lymphocytes/im [Immunology]
Complement Activation/im [Immunology]
Complement C3b/im [Immunology]
COVID-19/bl [Blood]
COVID-19/im [Immunology]
Female
Humans
Immunoglobulin M/bl [Blood]
Immunoglobulin M/im [Immunology]
Lymphocytes/im [Immunology]
Lymphopenia/bl [Blood]
Lymphopenia/im [Immunology]
Male
Middle Aged
Prevalence
SARS-CoV-2/im [Immunology]--Automated
MedStar Washington Hospital Center
Medicine/Infectious Disease
Journal Article
Research Support, Non-U.S. Gov't