Distinct Patterns of Autoantibodies Against G-Protein–Coupled Receptors in Chagas' Cardiomyopathy and Megacolon

Abstract

The percentage of asymptomatic Chagas' patients who had a specific AAB pattern and had a beta1-AAB level above a defined cutoff point mirrors very well the epidemiological situation, which showed that clinical manifestations develop in nearly 30% of Chagas' patients and cardiomyopathy in nearly 90% of them. We hypothesize that beta1-, beta2-, and M2-AAB measurement might be a useful tool for risk assessment in the indeterminate state of Chagas' disease to select patients for earlier involvement in care programs. However, prospective studies are needed to further evaluate this hypothesis.

Aptamer Neutralization of Beta1-Adrenoceptor Autoantibodies Isolated From Patients With Cardiomyopathies

“…Similar results were obtained when serum from Chagas' cardiomyopathy patients, 7 which contains a mixture of several AABs, was tested. Only beta1-AABs were neutralized by aptamer 110, whereas beta2-and M2-AABs were unaffected ( Figure 3B).…”

“…As recently described in detail, 7 IgGs were prepared from patient serum by stepwise ammonium sulfate precipitation. Briefly, 1 mL of patient serum and 660 L saturated ammonium sulfate solution were mixed (final concentration 40% ammonium sulfate) and incubated for 18 hours at 4°C.…”

Infection With Trypanosoma cruzi and Progression to Cardiomyopathy

“…17,18 Finally, autoantibodies directed to β 1 -and β 2 -adrenoreceptors and muscarinic-2 receptors have been documented in asymptomatic carriers and have been used to predict progression to cardiomyopathy, but larger studies are needed to validate these markers. 23 What is our current knowledge of the progression of Chagas disease in asymptomatic seropositive blood donors? This is an important question today because a significant number of asymptomatic T cruzi carriers have migrated to developed countries, of which the United States has the largest burden of infected individuals.…”

Autoantibodies in Heart Failure and Cardiac Dysfunction

“…et al 4 immune complexes, activating the complement system, binding to surface receptors, and influencing downstream signaling. [5][6][7][8][9] The exact triggers for induction of an autoimmune responses are not well known, but various human autoimmune diseases display a myosin heavy chain (MHC)-linked association (multiple sclerosis, graves' disease, myasthenia gravis, rheumatoid arthritis). 10 -14 Although, during the last years, it has been discovered that autoimmunity plays an important role in the pathogenesis of myocarditis and dilated cardiomyopathy (DCM) in genetically predisposed individuals, to our knowledge barely any of the available genetic studies in familial DCM has taken into account the autoimmune phenotype markers in the characterization of patients and relatives.…”