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.

Mechanisms of Primary Membranous Nephropathy

“…Risk alleles for THSD7A-associated MNs remain unclear. Collectively, the involvement of HLA-DQA1 and HLA-DRB1 in PLA2R-associated MN pathogenesis is consistent with the current knowledge for the importance of T-cell dependent and B-cell-mediated autoimmunity to anti-receptor-caused autoimmune diseases [ 73 ], which include the receptor PLA2R in PMN.…”

Natural autoantibodies to the gonadotropin-releasing hormone receptor in polycystic ovarian syndrome

“…A reason for the low prevalence of GnRH-R-aAb may be given in the nature of the protein as a GPCR, with only small portions of the protein exposed to the extracellular space, i.e., the N-terminus and the three small extracellular loops. This feature may have also contributed to the relatively low concentrations of the GnRH-R-aAb identified, barely surpassing the noise level in several of the statistically positive samples, leaving three samples only with GnRH-R-aAb concentrations in a considerable range that may be disease-relevant, as the disruptive effects of aAb on physiological or endocrine pathways usually correlates to aAb titer [ 36 ].…”

Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients

“…The DEGs dataset of these leukocytes is displayed in Figure 2C and Dataset 3, except for monocytes, which were unable to be analyzed due to insufficient cell numbers. Also, the deficiency of meaningful differential genes in plasma cells, T cells, and mast cells was probably owing to the technical limits of isolating insufficient corresponding cells, since previous studies have confirmed their contributions in IMN (31)(32)(33). Macrophages highly expressed genes responsible for the regulation of leukocyte activation (ZFP36L2, AXL, and RPS3), inflammatory response (KNG1, ELF3, CXCR4, and LY86), and the antigen processing and presentation as well as immune response-regulating signaling pathway (HLA-DPA1, HLA-DPB1, and HLA-DRB1) (Figures 2D, E).…”