The vascular basement membrane in systemic sclerosis skin: heterogeneity of type IV collagen

In systemic sclerosis (SS) changes in the dermal microvasculature include endothelial cell damage, a reduction in the number of vessels, and vascular basement membrane thickening. The basement membrane is a critical component of the vessel, and alterations in its structure may lead to changes in the surrounding tissue. In SS the altered basement membrane is associated with the subsequent development of fibrosis. To investigate the relationship between vascular basement membrane changes in affected skin and disease progression, immunohistochemical analyses were performed using both polyclonal and monoclonal antibodies against type IV collagen, the major basement membrane collagen. Using two monoclonal antibodies directed against different conformational epitopes within the (alpha 1)2 (alpha 2) helical domain, type IV collagen was detected in normal skin, and uninvolved SS skin, but not in later grades of disease. Identical results were obtained using a monoclonal antibody against a sequential determinant on the denatured alpha 1 (IV) chain. The use of a polyclonal antibody, however, showed that type IV collagen was present in all grades of disease, suggesting an alteration in the composition of type IV collagen with disease progression.