Toh Bh

Smooth muscle autoantibody (SMA) was first found in the sera of patients with chronic active hepatitis and subsequently in the sera of patients with other autoimmune liver diseases, viral infections, certain cancers, heroin addicts and female infertility. SMA from patients with chronic active hepatitis reacts with many muscle and 'non-muscle' tissues while SMA from patients with other diseases usually reacts only with smooth muscle. These differences in immunofluorescent staining reactions suggest that SMA is a heterogeneous group of autoantibodies reactive with different smooth muscle autoantigens. As further evidence for this are findings that broad-reacting SMA can be absorbed out by actin, whereas autoantibodies reactive only with smooth muscle cannot, and that different SMAs give different immunofluorescent staining patterns using fibroblasts in tissue culture. Such staining patterns correspond to reactivity with either microfilaments, microtubules or intermediate filaments, ubiquitous cytoplasmic structures which make up the 'cytoskeleton'. Autoantibodies to actin-like microfilaments appear specific for chronic active hepatitis, autoantibodies to microtubules occur in infectious mononucleosis whereas autoantibodies to intermediate filaments occur in infectious hepatitis, chickenpox, measles and mumps. Predictably, future studies will show that presence of SMA with specificities for other proteins in the three types of cytoplasmic filaments, and given more information on antigenicity of the proteins and pathogenicity of the corresponding autoantibodies.

The origins of autoantibodies remain largely unknown. Burnet suggested that self-reactive clones of B lymphocytes are deleted during ontogeny and that 'forbidden' clones of autoantibody-producing B lymphocytes arise as a consequence of somatic mutation of the variable regions of immunoglobulin genes. The alternative view, which is gaining increasing support, is that autoreactive B cells are present in all normal individuals but are held in check by control mechanisms, e.g. by the idiotypic network of Jerne. Autoantibodies segregate with clusters of autoimmune diseases and are useful diagnostic markers of these diseases. The autoantigens targeted by these autoantibodies are largely unknown. The precise molecular characteristics of these autoantigens are currently under active investigation by immunochemical and recombinant DNA methods. Precise definition of these autoepitopes should lead to sensitive immunoassays and studies directed at determining the pathogenicity of the autoantigens. The new knowledge gained in this way may lead to successful restoration of tolerance to self antigens.