Adhesion and lymphocyte costimulatory molecules in systemic rheumatic diseases

Adhesion molecules expressed on the surface of immune cells transduce a variety of cell-activating signals and mediate important interactions by binding to multiple specific counter-receptors expressed on other cells or on extracellular matrix components. A large number of aberrations in the expression of cell-bound molecules at the mRNA and protein level in vivo have been described in patients with autoimmune connective tissue diseases. In vitro studies suggest the presence of functional abnormalities of adhesive pathways, at least at some points of the disease. Increased circulating levels of isoforms of several adhesion molecules have also been demonstrated in these patients. The possible involvement in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome and systemic sclerosis of E-, P- and L-selectins, of some integrins and of several adhesion molecules of the immunoglobulin superfamily that in addition participate in lymphocyte costimulation will be discussed in this review. Further studies on migration and recruitment patterns of immune cells into inflamed tissues, as well as on possible defects of lymphocyte activation in these patients, are expected to expand our knowledge on systemic autoimmune responses and identify targets for specific immunotherapy.