Receptor autoimmunity: diagnostic and therapeutic implications

Abstract

Receptor autoimmunity is one of the ways in which autoimmune diseases appear in humans. Graves' disease, myasthenia gravis, idiopathic membranous nephropathy, and autoimmune acute encephalitis are the major autoimmune diseases belonging to this particular group. Receptor autoimmune disease are dependent on the presence of autoantibodies directed against cell-surface antigens, namely TSH receptor in thyrocytes, acetylcholine receptor in neuromuscular junction, phospholipase 2 receptor in podocytes, and NMDA receptor in cortical neurons. In this article we outline the distinctive features of receptor autoimmunity and the specific relationship between the autoimmunology laboratory and the presence/concentration of autoantibodies. Some immunological features distinguish receptor autoimmunity. Anti-receptor autoantibody pathologies are considered T cell-dependent, B-cell-mediated autoimmune disorders: the knowledge about the presence of circulating and/or localized autoantibodies to target organs and identification of autoantigens involved in the autoimmune reaction is of paramount importance. Due to the close correlation between the concentration of anti-receptor autoantibodies, the autoimmune target of some cell-surface receptors and the intensity of symptoms, the measurement of these immunoglobulins has become central to diagnose autoimmune diseases in all affected patients, not just in clinically dubious cases. The measurement of autoantibodies is also relevant for differential diagnosis of autoimmune and non-autoimmune forms with similar symptoms. From the methodological point of view, quantitative immunoassay methods of measurement should be preferred over semi-quantitative ones, for the capacity of the first class of methods to define precisely the reference ranges and decision levels overcoming the measurement uncertainty of semi-quantitative methods.

Keywords: Autoimmune acute encephalitis; Cell-surface receptors; Graves’ disease; Idiopathic membranous nephropathy; Immunoassays; Myasthenia gravis; Receptor autoantibodies.