Autoantibodies as Endogenous Modulators of GPCR Signaling

Endogenous self-reactive autoantibodies (AAs) recognize a range of G-protein-coupled receptors (GPCRs). They are frequently associated with cardiovascular, neurological, and autoimmune disorders, and in some cases directly impact disease progression. Many GPCR AAs modulate receptor signaling, but molecular details of their modulatory activity are not well understood. Technological advances have provided insight into GPCR biology, which now facilitates deeper understanding of GPCR AA function at the molecular level. Most GPCR AAs are allosteric modulators and exhibit a broad range of pharmacological properties, altering both receptor signaling and trafficking. Understanding GPCR AAs is not only important for defining how these unusual GPCR modulators function in disease, but also provides insight into the potential use and limitations of using therapeutic antibodies to modulate GPCR signaling.

Automated summary

Endogenous self-reactive autoantibodies can recognize G-protein-coupled receptors and are often associated with various diseases; they modulate receptor signaling, but the molecular details of their modulatory activity are still unclear. Technological advances have provided new opportunities to understand the function of GPCR AAs, which also helps to explore the potential roles and limitations of therapeutic antibodies in modulating GPCR signaling.