tetano
Editor, Senior Moderator
Front Immunol
. 2024 Apr 17:15:1352330.
doi: 10.3389/fimmu.2024.1352330. eCollection 2024. Prevalence of anti-lymphocyte IgM autoantibodies driving complement activation in COVID-19 patients
Ainhoa Pérez-Díez[SUP] 1 [/SUP], Xiangdong Liu[SUP] 1 [/SUP], Stephanie Calderon[SUP] 1 [/SUP], Ashlynn Bennett[SUP] 1 [/SUP], Andrea Lisco[SUP] 1 [/SUP], Anela Kellog[SUP] 1 [/SUP], Frances Galindo[SUP] 2 [/SUP], Matthew J Memoli[SUP] 3 [/SUP], Joseph M Rocco[SUP] 1 [/SUP], Brian P Epling[SUP] 1 [/SUP], Elizabeth Laidlaw[SUP] 1 [/SUP], Mike C Sneller[SUP] 1 [/SUP], Maura Manion[SUP] 1 [/SUP], Glenn W Wortmann[SUP] 4 [/SUP], Rita Poon[SUP] 5 [/SUP], Princy Kumar[SUP] 6 [/SUP], Irini Sereti[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID-19; anti-lymphocyte Ab; autoantibodies; complement activation; complement deposition; complement-dependent cytotoxicity; convalescent COVID-19; lymphopenia.
. 2024 Apr 17:15:1352330.
doi: 10.3389/fimmu.2024.1352330. eCollection 2024. Prevalence of anti-lymphocyte IgM autoantibodies driving complement activation in COVID-19 patients
Ainhoa Pérez-Díez[SUP] 1 [/SUP], Xiangdong Liu[SUP] 1 [/SUP], Stephanie Calderon[SUP] 1 [/SUP], Ashlynn Bennett[SUP] 1 [/SUP], Andrea Lisco[SUP] 1 [/SUP], Anela Kellog[SUP] 1 [/SUP], Frances Galindo[SUP] 2 [/SUP], Matthew J Memoli[SUP] 3 [/SUP], Joseph M Rocco[SUP] 1 [/SUP], Brian P Epling[SUP] 1 [/SUP], Elizabeth Laidlaw[SUP] 1 [/SUP], Mike C Sneller[SUP] 1 [/SUP], Maura Manion[SUP] 1 [/SUP], Glenn W Wortmann[SUP] 4 [/SUP], Rita Poon[SUP] 5 [/SUP], Princy Kumar[SUP] 6 [/SUP], Irini Sereti[SUP] 1 [/SUP]
Affiliations
- PMID: 38694513
- PMCID: PMC11061367
- DOI: 10.3389/fimmu.2024.1352330
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.
Keywords: COVID-19; anti-lymphocyte Ab; autoantibodies; complement activation; complement deposition; complement-dependent cytotoxicity; convalescent COVID-19; lymphopenia.