Glycosaminoglycans in autoimmunity

Abstract

Alteration of the distribution pattern and composition of glycosaminoglycans (GAG) and proteoglycans may play an important role in the development of autoimmune diseases. Recent experiments indicate that anti-DNA antibodies cross-reacting with hyaluronic acid, heparan sulphate and chondroitin sulphate are present in patients with systemic lupus erythematosus. Furthermore, elevated hyaluronic acid antibody levels correlating with the disease score have been found in the sera of patients with autoimmune thyroid disease in comparison to controls. In vitro, T lymphocytes from patients with this disease increased the production of hyaluronic acid by cultured human retro-orbital fibroblasts. Fibroblast stimulation, as well as elevated collagen and GAG production, could be shown in chicken cell lines which spontaneously develop an autoimmune syndrome analogous to human scleroderma. To analyse the structure and distribution pattern of different GAG compounds in the tissues and body fluids of patients with autoimmune diseases a highly specific HPLC method was developed, which revealed increased urinary chondroitin sulphate and dermatan sulphate concentrations in patients with autoimmune thyroid disease in comparison to controls, concentrations which were positively correlated with disease severity and disease activity. Furthermore, the renal GAG excretion in patients with autoimmune diabetes mellitus was studied, and markedly higher excretion in patients compared to healthy controls was found, which was correlated with the duration of the disease and diabetic late complications. Thus, GAG polysaccharides not only appear to play a major role in the pathogenesis of autoimmune diseases, but have been successfully introduced as an activity marker of the disease.