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  • Review Article
  • Published:

Functional autoantibodies targeting G protein-coupled receptors in rheumatic diseases

Nature Reviews Rheumatology volume 13, pages 648–656 (2017)Cite this article

Subjects

Key Points

  • Certain autoantibodies specific for G protein-coupled receptors (GPCRs) can regulate the function of these cell surface receptors and are known as functional autoantibodies

  • Functional autoantibodies targeting different GPCRs might influence the outcome of autoimmune diseases

  • Growing evidence points to a pathological role of autoantibodies against endothelin receptor type A (ETAR) and type 1 angiotensin II receptor (AT1R)

  • Anti-AT1R and anti-ETAR autoantibodies can trigger the same signalling pathways as those activated by endogenous ligands, ultimately regulating the same cellular events

  • The concentration of anti-GPCR autoantibodies in the serum of healthy individuals is usually lower than in that of patients with autoimmune disorders

Abstract

G protein-coupled receptors (GPCRs) comprise the largest and most diverse family of integral membrane proteins that participate in different physiological processes such as the regulation of the nervous and immune systems. Besides the endogenous ligands of GPCRs, functional autoantibodies are also able to bind GPCRs to trigger or block intracellular signalling pathways, resulting in agonistic or antagonistic effects, respectively. In this Review, the effects of functional GPCR-targeting autoantibodies on the pathogenesis of autoimmune diseases, including rheumatic diseases, are discussed. Autoantibodies targeting β1 and β2 adrenergic receptors, which are expressed by cardiac and airway smooth muscle cells, respectively, have an important role in the development of asthma and cardiovascular diseases. In addition, high levels of autoantibodies against the muscarinic acetylcholine receptor M3 as well as those targeting endothelin receptor type A and type 1 angiotensin II receptor have several implications in the pathogenesis of rheumatic diseases such as Sjögren syndrome and systemic sclerosis. Expanding the knowledge of the pathophysiological roles of autoantibodies against GPCRs will shed light on the biology of these receptors and open avenues for new therapeutic approaches.

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Figure 1: The role of GPCRs in the regulation of human physiology.
Figure 2: Pathological effects of anti-GPCRs autoantibodies interfering with neuronal transmission.

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Acknowledgements

We thank Dr Lena F Schimke-Marques and Dr. Antje Müller from the Department of Rheumatology, University of Lübeck for her critical reading of the manuscript. We would also like to acknowledge the support and funding from the intramural grant of the University of Lübeck, German Systemic Sclerosis Network (DNSS), DFG grant RI 1056-11-1/2, Actelion Pharmaceutical GmbH Germany, GSK, CellTrend, Scleroderma Foundation, and Mirjam Lichy Foundation.

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  1. Department of Rheumatology and Clinical Immunology, University of Lübeck, Ratzeburger Allee 160, Lübeck, 23538, Germany

    Otavio Cabral-Marques & Gabriela Riemekasten

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  1. Otavio Cabral-Marques
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All the authors researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Gabriela Riemekasten.

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Cabral-Marques, O., Riemekasten, G. Functional autoantibodies targeting G protein-coupled receptors in rheumatic diseases. Nat Rev Rheumatol 13, 648–656 (2017). https://doi.org/10.1038/nrrheum.2017.134

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