- Paper Report
- Open Access
Does HCMV infection trigger the vascular damage in SSc?
- Oliver Distler1
© Current Science Ltd 2000
- Published: 9 November 2000
- endothelial cells
Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular and immunological abnormalities. The aim of this study was to identify disease-relevant autoantigens.
Using random peptide library screening, a peptide was identified that was recognized by serum IgG from most SSc patients, but not from healthy controls and only by a minority of serum IgG from rheumatoid arthritis and systemic lupus erythematosus patients. Affinity purified IgG antibodies from the SSc sera against this peptide showed binding activity to different autoantigens such as fibrillarin and cytochrome C as well as to the human cytomegalovirus (HCMV) late protein UL94. In addition, the cross-reactive epitope of this peptide shared homology with the endothelial cell marker NAG-2. Antibodies against the SSc peptide and the HCMV late protein UL94 both specifically recognized integrin-NAG-2 complexes. When human umbilical vein endothelial cells (HUVECs) were incubated with the affinity-purified antibodies, the antibodies bound to the cell surface, and a dose- and time-dependent apoptosis-inducing effect was found that was inhibited by preabsorption with both the SSc and the viral peptide. Moreover, anti-NAG-2 antibodies induced apoptosis of HUVECs.
Random peptide library screening, ELISA, immunoprecipitation, internucleosomal DNA fragmentation measurement
Neidhart M, Kuchen S, Distler O, Bruhlmann P, Michel BA, Gay RE, Gay S: Increased serum levels of antibodies against human cytomegalovirus and prevalence of autoantibodies in systemic sclerosis.
Arthritis Rheum 1999, 42:389-392 (PubMed abstract).
Pandey JP, LeRoy EC: Current comment: human cytomegalovirus and the vasculopathies of autoimmune diseases (especially scleroderma), allograft rejection and coronary restenosis.
Arthritis Rheum 1998, 41:10-15.