Systemic sclerosis immunoglobulin G autoantibodies bind the human cytomegalovirus late protein UL94 and induce apoptosis in human endothelial cells

Systemic sclerosis is an autoimmune disease characterized by immunological and vascular abnormalities. Autoantibodies against intracellular antigens a re associated with particular clinical features of the disease(1), whereas autoantibodies against cell surface antigens may be pathogenic by inducing endothelial cell damage(2,3), considered the primary event in the pathogene sis of the disease. Latent human cytomegalovirus infection may contribute t o progression of systemic sclerosis through its ability to infect endotheli al cells(4); however, direct links between human cytomegalovirus infection and systemic sclerosis are still lacking(5). Molecular mimicry is one of th e mechanisms that account for the link between infection and autoimmunity(6 -8). Here we have identified an immunodominant peptide using systemic scler osis serum screening of a random peptide library; such peptide shares homol ogy with autoantigens and with the human cytomegalovirus late protein UL94 (ref. 9). Immunoglobulin C antibodies against the peptide affinity-purified from the sera of patients with systemic sclerosis specifically recognized the viral product and autoantigens; moreover, such antibodies induced endot helial cell apoptosis through specific interaction with the cell surface in tegrin-NAG-2 protein complex(10). Our results provide evidence that antibod ies against human cytomegalovirus cause apoptosis of endothelial cells(11), considered the initial pathogenic event of systemic sclerosis, and indicat e a previously unknown mechanism for the etiological link between human cyt omegalovirus infection and autoimmunity.