Systemic Sclerosis (SSc) is a disease of unknown etiology characterized by fibrosis, small vessel fibrointimal proliferation, and autoantibody production; all possibly resulting from involvement of T-cells. Organ complications can be extensive, significantly increasing morbidity and mortality. Previous studies from our laboratory show evidence of oligoclonal T-cells proliferation in the skin and peripheral blood of SSc patients, in response to currently unidentified antigens. Putative antigens include microchimeric cells, CMV and DNA topoisomerase-l. The project aims to determine the specific role(s) T-cells play in SSc pathogenesis, and potential predictor molecular signatures that predispose patients to the complications of the disease.
Specific aims are to, 1)-determine the origin of clonally-expanded gamma/delta T-cells, using in-situ hybridization; 2)- identify antigens recognized by these clonally-expanded T-cells in skin biopsies and peripheral blood samples from maternal and offspring SSc patients, via transducing full-length TCR chain transcripts into beta chain TCR-negative mutant Jurkat T-cells or delta-chain TCR-negative mutant MOLT-13 T-cells and other appropriate cell lines; 3)-Use DNA microarray to assess risks for complications; and relate to sex and race.
