Immunologic aspects of scleroderma

Activation of both cellular and humoral immunity are early events in systemic sclerosis (SSc) that appear to contribute to disease pathogenesis. Recent reports suggest that CD4+ and CD8+ T cells and a subset of gamma delta T cells each may play a role in the disease. Interest in potential profibrotic effects of transforming growth factor-beta in SSc continues. Expression of a variety of adhesion molecules is increased on fibroblasts and endothelial cells in SSc patients, as are circulating levels of the same molecules. Different autoantibody specificities are generated in B cells from tight-skin mice by use of identical VH genes, with similar V kappa genes but different J kappa segments. Centromeric proteins, topoisomerase I, RNA polymerases I, II, and III, fibrillarin, and upstream binding factor may become autoantibody targets in SSc because they are presented to the immune system as part of larger multiunit complexes. Homology between target autoantigens and infectious agents suggests that molecular mimicry initiates some autoantibody responses in SSc patients. Genetic factors influence the pattern of autoantibodies produced in different populations. Exogenous agents can induce autoantibodies in humans and mice that are similar to those seen in spontaneous SSc.