Anti-β1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease

Labovsky, Vivian; Smulski, Cristian R.; Gómez, Karina Andrea; Levy, Gabriela Vanesa; Levìn, Mariano J.

doi:10.1111/j.1365-2249.2007.03381.x

Cited by 61 publications

(40 citation statements)

References 40 publications

(73 reference statements)

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“…Another promising option would be the inhibition or elimination of the high percentage of pathogenetic autoantibodies found in chronic Chagas' heart disease [66,67]. It has been shown for patients with dilated cardiomyopathy and also recently suggested for patients with Chagas' cardiomyopathy that a significant benefit could be achieved if the autoantibodies against the beta 1-receptor were eliminated by immunoabsorption [68][69][70][71]. Since the current immunoabsorption techniques for beta 1-receptor autoantibodies in DCM are based on the elimination of the whole IgG fraction, they might be suitable for chronic Chagas' disease patients carrying autoantibodies against the beta 1-receptor and also for those carrying autoantibodies against the beta 2-and muscarinergic 2-receptors.…”

Section: Therapymentioning

confidence: 97%

Chronic Chagas’ heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine

et al. 2010

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Chagas' disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America. Nearly 30% of infected patients develop life-threatening complications, and with a latency of 10-30 years, mostly Chagas' heart disease which is currently the major cause of morbidity and mortality in Latin America, enormously burdening economic resources and dramatically affecting patients' social and labor situations. Because of increasing migration, international tourism and parasite transfer by blood contact, intrauterine transfer and organ transplantation, Chagas' heart disease could potentially become a worldwide problem. To raise awareness of this problem, we reflect on the epidemiology and etiopathology of Chagas' disease, particularly Chagas' heart disease. To counteract Chagas' heart disease, in addition to the general interruption of the infection cycle and chemotherapeutic elimination of the infection agent, early and effective causal or symptomatic therapies would be indispensable. Prerequisites for this are improved knowledge of the pathogenesis and optimized patient management. From economic and logistics viewpoints, this last prerequisite should be performed using laboratory medicine tools. Consequently, we first summarize the mechanisms that have been suggested as driving Chagas' heart disease, mainly those associated with the presence of autoantibodies against G-protein-coupled receptors; secondly, we indicate new treatment strategies involving autoantibody apheresis and in vivo autoantibody neutralization; thirdly, we present laboratory medicine tools such as autoantibody estimation and heart marker measurement, proposed for diagnosis, risk assessment and patient guidance and lastly, we critically reflect upon the increase in inflammation and oxidative stress markers in Chagas' heart disease.

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Section: Therapymentioning

confidence: 97%

Chronic Chagas’ heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine

et al. 2010

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“…To this end, a linear 26-meric peptide, which corresponds to the 2 nd extracellular loop (amino acid position 197-222) of the human ␤1-AR, was immobilized onto microtiter plates. 16,17 This kind of assay is fully high-throughput screening adapted, but its use as a screening assay with diagnostic relevance had not yet been simultaneously investigated in a larger population of patients and age-matched control subjects who did not report any known heart disease.…”

Section: Discussionmentioning

confidence: 99%

Detection of Anti–β1-AR Autoantibodies in Heart Failure by a Cell-Based Competition ELISA

Holthoff

Zeibig

Jahns-Boivin

et al. 2012

Circulation Research

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Rationale: Autoantibodies directed against the second extracellular loop of the cardiac ␤1-adrenergic receptor (␤1-AR) are thought to contribute to the pathogenesis of dilated cardiomyopathy (DCM) and Chagas heart disease. Various approaches have been used to detect such autoantibodies; however, the reported prevalence varies largely, depending on the detection method used.Objective: We analyzed sera from 167 DCM patients (ejection fraction <45%) and from 110 age-matched volunteers who did not report any heart disease themselves, with an often used simple peptide-ELISA approach, and compared it with a novel whole cell-based ELISA, using cells expressing the full transgene for the human ␤1-AR. Additionally, 35 patients with hypertensive heart disease with preserved ejection fraction were investigated. Methods and Results:The novel assay was designed according to the currently most reliable anti-TSH receptor antibody-ELISA used to diagnose Graves disease ("third-generation assay") and also detects the target antibodies by competition with a specific monoclonal anti-␤1-AR antibody (␤1-AR MAb) directed against the functionally relevant ␤1-AR epitope. Anti-␤1-AR antibodies were detected in Ϸ60% of DCM patients and in Ϸ8% of healthy volunteers using the same cutoff values. The prevalence of these antibodies was 17% in patients with hypertensive heart disease. Anti-␤1-AR antibody titers (defined as inhibition of ␤1-AR MAb-binding) were no longer detected after depleting sera from IgG antibodies by protein G adsorption. In contrast, a previously used ELISA conducted with a linear 26-meric peptide derived from the second extracellular ␤1-AR loop yielded a high number of false-positive results precluding any specific identification of DCM patients. Conclusions:We established a simple and efficient screening assay detecting disease-relevant ␤1-AR autoantibodies in patient sera yielding a high reproducibility also in high throughput screening. The assay was validated according to "good laboratory practice" and can serve as a companion biodiagnostic assay for the development and evaluation of antibody-directed therapies in antibody-positive heart failure. (Circ Res. 2012;111:675-684.)

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“…In this context, the elimination of pathogenetic AABs, such as the pathogenic β 1-AABs, via apheresis techniques has been suggested for Chagas heart disease [90] . The idea of using apheresis in the treatment of Chagas heart disease is supported by the well-documented benefits of β -1-AAB immunoadsorption in patients with DCM [91] .…”

Section: Therapymentioning

confidence: 99%

Chronic Chagas disease: from basics to laboratory medicine

Haberland

Saravia

Wallukat

et al. 2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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Chagas disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America and has huge potential to become a worldwide problem, due to increasing migration, and international tourism, as well as infectant transfer by blood contact and transfusion, intrauterine transfer, and organ transplantation. Nearly 30% of chronically-infected patients become symptomatic, often with a latency of 10–30 years, developing life-threatening complications. Of those, nearly 90% develop Chagas heart disease, while the others manifest gastrointestinal disease and neuronal disorders. Besides interrupting the infection cycle and chemotherapeutic infectant elimination, starting therapy early in symptomatic patients is important for counteracting the disease. This would be essentially supported by optimized patient management, involving risk assessment, early diagnosis and monitoring of the disease and its treatment. From economic and logistic viewpoints, the tools of laboratory medicine should be especially able to guarantee this. After summarizing the basics of chronic Chagas disease, such as the epidemiological data, the pathogenetic mechanisms thought to drive symptomatic Chagas disease and also treatment options, we present tools of laboratory medicine that address patient diagnosis, risk assessment for becoming symptomatic and guidance, focusing on autoantibody estimation for risk assessment and heart marker measurement for patient guidance. In addition, increases in levels of inflammation and oxidative stress markers in chronic Chagas disease are discussed.

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Anti-β1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease

Cited by 61 publications

References 40 publications

Chronic Chagas’ heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine

Chronic Chagas’ heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine

Detection of Anti–β1-AR Autoantibodies in Heart Failure by a Cell-Based Competition ELISA

Chronic Chagas disease: from basics to laboratory medicine

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