HIV patients produce IgM autoantibodies with anti-lymphocyte reactivities and complement-mediated lytic function that persist after anti-retroviral therapy

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

We have previously found that in the setting of another viral infection, such as SARS-CoV-2, infected individuals harbored IgM, and not IgG, auto-antibodies (auto-Ab) that persisted after disease recovery. We wondered if people living with HIV (PLWH) might also have IgM auto-Ab in conjunction to the previously described IgG auto-Ab. In a pilot study and using a flow-based assay, we found that at four to 112 weeks after initiation of anti-retroviral therapy (ART), 83% of PLWH had IgM autoAb specific for targets present on CD4, CD8 and/or B lymphocyte membranes. We also found IgG auto-Ab albeit in much lower percentage of patients. Plasma containing auto-reactive IgM Ab induced lymphocyte killing by complement dependent cytotoxicity (CDC) in vitro, which was dependent on the presence of both active complement and IgM. The degree of plasma CDC activity against CD4 T cells inversely correlated with its respective patient CD4 counts. In addition, 53% of PLWH displayed C3b complement deposition on their CD4 T cells, which correlated with the patient’s level of anti-CD4 IgM Ab but not with IgG anti-CD4 Ab, suggesting that IgM anti-CD4 Ab is able to trigger complement activation both in vitro and in vivo. In a longitudinal evaluation of 39 PWH, we found the prevalence of IgM or/and IgG ALAb to be the highest before or soon after ART initiation with 74% of participants having anti-CD4 Ab, being IgM the predominant isotype. Importantly, the Ab persisted for at least two years of ART, remaining detectable in 49% of PWH.