Autoimmunity induced by human cytomegalovirus in patients with systemic lupus erythematosus

healthy people, a primary infection with human cytomegalovirus (HCMV) is often mild or even asympto-matic, but may cause a mononucleosis-like syndrome with fever, arthralgia, fatigue, thrombo cyto penia, and anemia. During acute infection, HCMV infection often leads to immune dysfunction, including both immuno-suppression 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 & Th erapy, 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 pp65 336–439 [1]. Immune reactivity against this peptide was found in 14 to 20% of patients with rheumatoid arthritis, Sjögren's syndrome, and systemic sclerosis but in only 4% of healthy controls. Immunization of BALB/c mice with pp65 336–439 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. Th ese observations suggest that the HCMV pp65 336–439 peptide elicits production of antibodies that cross-react with nuclear proteins and are pathogenic in genetically suscep tible 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 infl ammation may occur periodically (reviewed in [2]). Even though the virus may not trigger autoimmune disease, it may be reactivated by an initial infl ammatory insult and thereafter sustain and exacerbate infl ammatory processes by producing type I cytokines and by specifi c mecha nisms that induce infl ammation and autoimmune reac tions. For example, HCMV infection induces expression of cyclo-oxygenase-2 and 5-lipoxygenase and induces production of prostaglandin E 2 , leukotriene B 4 , and IL-6 – all potent infl ammatory mediators [3-5]. HCMV proteins alone will also drive immune reactions to nonself-peptides. By defi nition, auto immune reactions occur in the absence of a pathogen in the aff ected organ. Emerging evidence, however, suggests that HCMV proteins are common in tissues aff …