Immunologic aspects of scleroderma.
Now that the immune involvement in scleroderma is well established, attention is focused on defining the precise mechanisms in immune activation, the nature of autoantigens, the clinical description of disease subsets as defined by autoantibodies, the cytokine network, and the participation of various immune cells in the disease. Yet the exact trigger of immune involvement is still elusive. Interaction of immune cells with the vascular endothelium, through cell-cell interactions and the effect of cytokines, is one of the earliest changes in scleroderma. It is still unclear whether immune alteration follows or precedes endothelial changes. Nonetheless, involvement of the adhesion molecules cascade is well documented. A nucleolar location has been suggested for all of the major autoantigens in scleroderma, with the nucleolus as the primary autoantigen molecular structure. Topoisomerase-I homology to viral proteins continues to be the focus of investigation; however, molecular mimicry in scleroderma autoimmunity is still unproven. Enhanced expression and responses to interleukin-1 and interleukin-6 by scleroderma fibroblasts emphasize the interactive nature of fibroblasts and demonstrate the ability of nonimmune cells to produce immune mediators. Circulating autoantibodies to interleukin-6 and interleukin-8 add another dimension to our understanding of cytokine network regulation in scleroderma. Circulating markers reflecting T-cell activation in vivo continue to be observed. Adenosine deaminase is the most recent indicator described. Nonetheless, the exact phenotype of the principal effector T cell in scleroderma is still not known. A restricted usage of the V beta gene repertoire of the double-negative alpha/beta T cells propose this cell type as the alloreactive cell in scleroderma.(ABSTRACT TRUNCATED AT 250 WORDS)
Kahaleh
B
B
Division of Rheumatology, Medical College of Ohio, Toledo 43699.
D001323:Autoantibodies / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D006801:Humans; D008213:Lymphocyte Activation; D012595:Scleroderma, Systemic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D016207:Cytokines