Autoimmunity induced by human cytomegalovirus in patients with systemic lupus erythematosus

In healthy people, a primary infection with human cytomegalovirus (HCMV) is often mild or even asymptomatic, but may cause a mononucleosis-like syndrome with fever, arthralgia, fatigue, thrombocytopenia, and anemia. During acute infection, HCMV infection often leads to immune dysfunction, including both immunosuppression and autoimmune phenomena. HCMV infection results in production of autoantibodies, mainly against endothelial cells and smooth muscle cells, although anti-nuclear, anti-phospholipid, and anti-CD13 autoantibodies are also common. Emerging evidence implies that HCMV can precede the onset of auto-immune disease, and this is probably more common in individuals predisposed for autoimmunity.In a previous issue of Arthritis Research & Therapy, Hsieh and colleagues demonstrate that a majority of systemic lupus erythematosus (SLE) patients have antibodies to the C-terminus of pp65, in particular to the subfragment pp65336-439 [1]. Immune reactivity against this peptide was found in 14 to 20% of patients with rheumatoid arthritis, Sj？gren's syndrome, and systemic sclerosis but in only 4% of healthy controls. Immunization of BALB/c mice with pp65336-439 and C3b adjuvant resulted in production of multiple antibodies that recognize nuclear structures, including chromatin, centriole mitotic spindle type I/II, and double-stranded DNA, and the immunized mice had immunoglobulin deposition in kidney glomeruli [1]. Previously, this group showed that pp65 immunization induces early autoantibody production and glomerulonephritis in lupus-prone mice. These observations suggest that the HCMV pp65336-439 peptide elicits production of antibodies that cross-react with nuclear proteins and are pathogenic in genetically susceptible persons.HCMV is a ubiquitous pathogen that infects 60 to 90% of the world's population. After a primary infection, it resides in latently infected monocytes or premonocytic cells, and reactivation often driven by inflammation may occur periodically (