Its Paradoxical Binding In Vivo to the Apical Surface o f the Follicular Epi thel ium

Several autoantibodies have been described in autoimmune thyroid diseases with specificities for antigens localized to the ("microsomal") acinar cell cytoplasm, colloid space (thyroglobulin, second colloid antigen), and surface membrane (TSH-receptor and other as yet unidentified moieties) (1). If circulating antibodies play any direct role in the pathogenesis of human thyroid disease, for example by mediating cytolysis, or by blocking or stimulating function and growth (2), they must be able to interact in vivo with their specific antigens. This interaction will depend upon the accessibility of autoantigenic determinants on the cell surface, on basal membranes, and in the circulation, and the availability of adequate amounts of antibody in intravascular and interstitial fluids. Immunohistological examination of the affected target tissue, by direct immunofluorescence (IFL) l with labeled anti-immunoglobulin (Ig) or anti-complement sera, is an accepted way of looking for evidence of in vivo autoreactivity. Glands from patients with autoimmune thyroid disease have been repeatedly screened by this procedure and granular deposits of Ig often associated with complement, were described in the colloid, in the connective-tissue stroma and along the follicular basement membrane (FBM; references 3-6). Thyroglobulin is the most likely target for colloid-bound Ig and is also believed to be involved in some instances in immune complexes deposited around the FBM (7). On the other hand, no direct evidence was found under these conditions concerning binding in vivo of autoreactive Ig on the follicular epithelium, though the presence of Ig deposits on isolated cells from thyrotoxic glands has been mentioned (8). Recently, it has been established that the cytoplasmic microsomal autoantigen is also present on the cell surface of human thyroid cells maintained in monolayer cultures (9). The same cell surface autoantigen is involved in the complement-