Increased serum IgG antibody response to Merkel cell polyomavirus oncoproteins in patients with autoimmune rheumatic diseases.

Abstract

Autoimmune rheumatic diseases (AIRDs) encompass a spectrum of disorders with a partially understood pathogenesis. A role for polyomaviruses in AIRDs occurrence has been reported. However, the involvement of Merkel cell polyomavirus (MCPyV), the main causative factor of Merkel cell carcinoma (MCC), an aggressive skin neoplasm related to immunosuppression, in AIRDs is unknown. The prevalence/serological profiles of immunoglobulin G (IgG) antibodies to MCPyV large and small T (LT/sT) oncoproteins and viral capsid proteins 1 and 2 (VP1/2) were investigated herein in 540 immunosuppressive treatment-naive AIRD patients, encompassing 447 rheumatoid arthritis (RA) and 93 ankylosing spondylitis (AS) patients by seven MCPyV-specific immunoassays. Control sera from 500 healthy subjects (HS) and 128 MCC patients were included. MCPyV DNA and LT/VP1 mRNAs were evaluated in peripheral blood mononuclear cells (PBMCs) from 75 randomly selected AIRD patients. AIRD patients exhibited higher prevalence and levels (optical densities) of serum anti-oncoprotein IgGs (12%-13%, 0.2-0.6) compared to HS (2%-7%, 0.1-0.4), but lower than MCC patients (70%-83%, 0.2-0.7) (P < .05), with the increase being more pronounced in AS (24%-29%, 0.3-0.8) than in RA (9%-11%, 0.2-0.8) (P < .05). Conversely, similar rates and levels of serum anti-capsid proteins IgGs were determined in most cases between study and control groups (60%-73%, 0.1-0.3) (P > .05). Moreover, receiver operating characteristic (ROC) curves indicated that the MCPyV serology can discriminate AIRD patients from HS (P < .0001). A fraction (11%) of AIRD PBMCs tested MCPyV DNA (7.4 ± 2.6 [copy/104 cells]) and mRNA-positive (0.5-0.1 [1/ΔCt]), while matched sera showed high rates and levels of anti-oncoproteins IgGs (38%-75%, 0.2-2). Our study provides the first evidence that AIRD patients are immunologically responsive to MCPyV oncoproteins, with a fraction of these patients presenting an increased presentation of MCPyV LT and sT antigens, possibly due to viral LT/sT oncogene expression in their PBMCs. These data suggest an association between MCPyV infection and AIRDs pathogenesis.