Survivors of Ebola virus disease exhibit elevated levels of autoantibodies

Abstract

Abstract Survivors of Ebola virus disease (EVD) report a wide range of symptoms following recovery from acute viral infection, but underlying mechanisms are unclear. Many of these symptoms, collectively termed Post-Ebola Syndrome (PES), occur in the absence of detectable virus and resemble symptoms associated with autoimmune disease, such as arthralgia and myalgia, suggesting that EVD survivors may be experiencing a virus-induced autoimmune response. Studies in mice have shown that mice develop autoantibodies (autoAb) against HSP-60 and double stranded (ds) DNA that can bind to host tissues following Ebola virus (EBOV) infection. To determine if human EVD survivors also develop autoAb that may be associated with PES development, we profiled the humoral immune response of 354 survivors and 195 household contacts (HHC) from the 2014–2016 outbreak in Sierra Leone. Using Systems Serology, we measured the levels of antibodies against common autoantigens and found that EVD survivors had elevated levels of autoAb against dsDNA, HSP-60, IFNα, and citrullinated histone compared to HHC. As a subset of HHC were seropositive for EBOV glycoprotein (GP)-specific antibodies, separation of HHC into GP-seropositive and seronegative groups showed that the levels of autoAb in GP-seropositive HHC were elevated compared to GP-seronegative HHC, strongly suggesting that exposure/infection to EBOV tracks with presence of autoAb. As antibodies can activate innate immune cells via the antibody Fc domain, current studies are focused on analyzing the innate effector response mediated by these autoAb in EVD survivors and seropositive HHC. Together, our study highlights the potential role of autoAb in long-term sequelae associated with survival from EVD.