What Makes Antibodies Against G Protein-Coupled Receptors so Special? A Novel Concept to Understand Chronic Diseases

Abstract

Expressions of G protein-coupled receptors (GPCR) on immune and tissue resident cells are the consequence of the cellular environment, which is highly variable. As discussed here, antibodies directed to GPCR (GPCR abs), their levels and correlations to other abs, serve as biomarkers for various diseases. They also could reflect the individual interplay between the environment and the immune system. Thus, GPCR abs could display pathogenic chronic conditions and could help to identify disease-related pathways. Moreover, by acting as ligands to their corresponding receptors, GPCR abs modulate autoimmune as well as non-autoimmune diseases. This article introduces GPCR abs as drivers for diseases by their capability to induce a specific signaling and by determining immune cell homeostasis. The identification of the individual GPCR ab function is challenging but might be pivotal in the comprehension of the aetiology of diseases. This, hopefully, will lead to the identification of novel therapeutic strategies. This article provides an overview about concepts and recent developments in research. Accordingly, GPCR abs could represent ideal candidates for precision medicine. Here, we introduce the term antibodiom to cover the network of abs with GPCR abs as prominent players.

Autoantibodies to Vasoregulative G-Protein-Coupled Receptors Correlate with Symptom Severity, Autonomic Dysfunction and Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…GPCR AAB specifically bind to their corresponding receptors, which can have functional consequences. Both stimulating agonistic and inhibiting antagonistic effects were described [13,15,48]. Considering an agonistic function, several associations of AAB with symptoms that we found are plausible.…”

Autoantibodies and SARS-CoV2 infection: The spectrum from association to clinical implication: Report of the 15th Dresden Symposium on Autoantibodies

“…Unfortunately, this review could not cover the whole spectrum of presentations on this topic because the research data underlying some of the presentations were not yet published. This included presentations on the potential role of autoantibodies directed against G-protein coupled receptors (GPCR) [ 44 ] and autoantibodies to the angiotensin converting enzyme (ACE)2 [ 45 , 46 ]. It can be speculated that the first are involved in the clinical manifestations associated with Long-COVID because clinical manifestations resemble diseases, like fibromyalgia and silicon-induced autoimmunity, due to an autoantibody-mediated dysregulation of the autonomic nervous system [ 47 , 48 ].…”

Functionally Active Antibodies to the Angiotensin II Type 1-Receptor Measured by a Luminometric Bioassay Do Not Correlate With Clinical Manifestations in Systemic Sclerosis: A Comparison With Antibodies to Vascular Receptors and Topoisomerase I Detected by ELISA

“…This has, indeed, been postulated for antibodies to G-protein coupled receptors (GPCR). It has been argued that the secretion of anti-GPCR antibodies may suppress excessive immune responses and prevent tissue damage ( 48 ). The hypothesis that the functionally active anti-AT 1 R-antibodies may belong to the pool of naturally occurring antibodies is underlined by our observation that they have been been detected in a rather high prevalence of 70% in patients with viral and toxic liver diseases.…”