Autoimmune mediated G-protein receptor activation in cardiovascular and renal pathologies.
Antibodies directed against G-protein coupled receptors (GPCR) can act as allosteric receptor agonists or antagonists. Prototypic disease for agonistic antibody action is a Graves disease of the thyroid gland where antibodies that stimulate G-protein coupled thyroid-stimulating hormone receptor (TSHR) were first described 50 years ago. Myasthenia gravis is the prototype for antagonistic autoimmune actions, where antibodies directed against the nicotinic acetylcholine receptor (AChR) cause blockade of neuromuscular junctions. Antibodies and B-cells are increasingly recognised as major modulators of various cardiovascular and renal pathologies. We aim to critically review the notion that antibodies targeting other GPCRs may amplify or cause various cardiovascular and renal pathologies and summarise the current state of research, as well as perspectives in diagnostic and therapeutic strategies. In terms of targets we will focus on the alpha-adrenergic receptor (alpha(1)AR), the beta-adrenergic receptor (beta(1)AR), and the angiotensin II type 1 receptor (AT(1)R).
Department of Nephrology and Intensive Care Medicine, Charité Campus Virchow Clinic, Berlin, Germany. duska.dragun@charite.de
Duska
D
Dragun
Aurélie
A
Philippe
Rusan
R
Catar
Björn
B
Hegner
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007167:Immunotherapy; D007674:Kidney Diseases / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D011237:Predictive Value of Tests; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology; D018340:Receptors, Adrenergic, alpha-1 / Q000276:immunology; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000276:immunology*; D015398:Signal Transduction
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D001323:Autoantibodies; D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D043562:Receptors, G-Protein-Coupled