Abstract
Autoantibodies directed against G-protein-coupled receptors (GPCR-AAB), an autoantibody type discovered in the 1970s, affect functionally their targets and are therefore called functional autoantibodies. GPCR-AAB are increasingly accepted as the origin or amplifier of various diseases. Here, we describe the present “gold standard” for measurement of GPCR-AAB in human blood. This bioassay monitors the chronotropic activity of GPCR-AAB by recording the spontaneous beating of cultured neonatal rat cardiomyocytes. The construction of this bioassay and its procedure and standardization for GPCR-AAB measurement are described in detail and also include the application of the bioassay for GPCR-AAB differentiation related to first the targeted receptors and IgG subclasses carrying the GPCR-AAB and second the extracellular receptor-binding site and specific epitopes targeted by the GPCR-AAB.
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References
Salamunić I (2010) Laboratory diagnosis of autoimmune diseases – new technologies, old dilemmas. Biochem Med 20:45–56
Pyle GA, Petersen VB, Hall R (1977) Interaction of thyroid-stimulating antibodies with the human thyrotrophin receptor. J Endocrinol 75:401–407
Cossio PM, Diez C, Szarfman A, Kreutzer E, Candiolo B, Arana RM (1974) Chagasic cardiopathy. Demonstration of a serum gamma globulin factor which reacts with endocardium and vascular structures. Circulation 49:13–21
Sterin-Borda L, Cossio PM, Gimeno MF, Gimeno AL, Diez C, Laguens RP, Meckert PC, Arana RM (1976) Effect of chagasic sera on the rat isolated atrial preparation: immunological, morphological and function aspects. Cardiovasc Res 10:613–622
Borda E, Pascual J, Cossio P, De la Vega M, Arana R, Sterin-Borda L (1984) A circulating IgG in Chagas’ disease which binds to ß-adrenoceptors of myocardium and modulates their activity. Clin Exp Immunol 57:679–686
Chen CR, Tanaka K, Chazenbalk GD, McLachlan SM, Rapoport B (2001) A full biological response to autoantibodies in Graves’ disease requires a disulfide-bonded loop in the thyrotropin receptor N terminus homologous to a laminin epidermal growth factor-like domain. J Biol Chem 276:14767–14772
Wallukat G, Schimke I (2014) Agonistic autoantibodies directed against G-protein-coupled receptors and their relationship to cardiovascular diseases. Semin Immunopathol 36:351–363
Bornholz B, Wallukat G, Roggenbuck D, Schimke I (2017) Autoantibodies against G-protein-coupled receptors in cardiovascular diseases: basics and diagnostics. In: Nussinovitch U (ed) The heart in rheumatologic, inflammatory and autoimmune diseases: pathophysiology, clinical aspects and therapeutic approaches. Academic Press, London. isbn:9780128032671
Becker NP, Müller J, Göttel P, Wallukat G, Schimke I (2017) Cardiomyopathy – an approach to the autoimmune background. Autoimmun Rev 16:269–286
Wallukat G, Wollenberger A (1987) Effects of the gamma globulin fraction of patients with allergic asthma and dilated cardiomyopathy on chronotropic beta adrenoceptor function in cultured neonatal rat heart myocytes. Biomed Biochim Acta 46:S634–S639
Boivin-Jahns V, Jahns R, Boege F (2018) Relevant effects of beta1-adrenoceptor autoantibodies in chronic heart failure. Front Biosci (Landmark Ed) 23:2146–2156
Nguemo F, Saric T, Pfannkuche K, Watzele M, Reppel M, Hescheler J (2012) In vitro model for assessing arrhythmogenic properties of drugs based on high-resolution impedance measurements. Cell Physiol Biochem 29:819–832
Nikolaev VO, Boivin V, Störk S, Angermann CE, Ertl G, Lohse MJ, Jahns R (2007) A novel fluorescence method for the rapid detection of functional beta1-adrenergic receptor autoantibodies in heart failure. J Am Coll Cardiol 50:423–431
Preuss B, Tunaru S, Henes J, Offermann S, Klein R (2014) A novel luminescence-based method for the detection of functionally active antibodies to muscarinic acetylcholine receptors of the M3 type (mAchR3) in patients’ sera. Immunology 177:179–189
Li H, Kem DC, Reim S, Khan M, Vanderlinde-Wood M, Zillner C, Collier D, Liles C, Hill MA, Cunningham MW, Aston CE, Yu X (2012) Agonistic autoantibodies as vasodilators in orthostatic hypotension: a new mechanism. Hypertension 59:402–408
Li H, Yu X, Liles C, Khan M, Vanderlinde-Wood M, Galloway A, Zillner C, Benbrook A, Reim S, Collier D, Hill MA, Raj SR, Okamoto LE, Cunningham MW, Aston CE, Kem DC (2014) Autoimmune basis for postural tachycardia syndrome. J Am Heart Assoc 3:e000755. https://doi.org/10.1161/JAHA.113.000755
Wallukat G, Wollenberger A, Morwinski R, Pitschner HF (1995) Anti-beta 1-adrenoceptor autoantibodies with chronotropic activity from the serum of patients with dilated cardiomyopathy: mapping of epitopes in the first and second extracellular loops, vol 27, pp 397–406
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Wallukat, G., Wenzel, K., Schimke, I. (2019). Analytics of Functional Autoantibodies in Patients with Chagas Disease. In: Gómez, K., Buscaglia, C. (eds) T. cruzi Infection. Methods in Molecular Biology, vol 1955. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9148-8_19
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DOI: https://doi.org/10.1007/978-1-4939-9148-8_19
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