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Evidence of autoantibodies against cardiac troponin I and sarcomeric myosin in peripartum cardiomyopathy

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Abstract

Peripartum cardiomyopathy (PPCM) is a major cause of pregnancy-related maternal heart failure that develops towards the end of pregnancy or in the months following delivery. In small retrospective case series, autoimmune responses in the pathogenesis of PPCM have been proposed upon identification of autoantibodies (AABs) to cardiac antigens. However, their clinical and prognostic relevance still remain unclear. In this study, we evaluated the presence of circulating AABs against cardiac sarcomeric myosin (MHC) and troponin I (TnI) in the sera of PPCM patients and in relation to clinical presentation. In this case–control study, 70 patients diagnosed with PPCM and 50 pregnancy-matched healthy women with normal cardiac function were enrolled. Clinical assessment, echocardiography and blood tests were performed at baseline and at 6 ± 2 months follow-up. The presence of serum AABs against MHC (anti-MHC) and TnI (anti-TnI) was determined with a custom-made enzyme-linked immunosorbent assay (ELISA). The seropositivity for these AABs was correlated with the severity of LV dysfunction and the occurrence of pericardial effusion indicative of perimyocardial inflammation at baseline. Potential impact of these AABs on disease progression was evaluated with regard to functional (left ventricular ejection fraction) and clinical improvement at follow-up. Either anti-MHC or anti-TnI or both AABs were detected in the serum of 46 % of PPCM patients and in 8 % of healthy controls. In PPCM the presence of either one of these AABs was associated with significantly lower baseline LVEF and lower rate of full cardiac recovery at follow-up. Patients who were seropositive for anti-TnI AABs showed more frequently pericardial effusion indicative of a more pronounced immune response of the peri-/myocardium in these patients. Further studies are required to clarify cellular and molecular circuits leading to elevated levels of AABs and their pathophysiological relevance for disease initiation and progression in PPCM.

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Acknowledgments

We thank B. Ritter, S. Gutzke, M. Jungesblut and S. Tammen for excellent assistance and Dr. Mirco Müller and Anna-Maria Müller for proofreading. We thank all clinical centers and patients who provided data and blood samples for the German registry. This study was supported by the German Research Foundation (DFG), the German Federal Ministry of Education and Research (BMBF) and the Cluster of Excellence “Regenerative Biology to Reconstructive Therapy” (Rebirth). Dr. Arash Haghikia received a scholarship from the “Junge Akademie” program of Hannover Medical School.

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Authors and Affiliations

  1. Department of Cardiology and Angiology, Hannover Medial School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Arash Haghikia, Johann Bauersachs & Denise Hilfiker-Kleiner

  2. Department of Cardiology, Pulmonology, and Vascular Medicine, University of Heidelberg, Heidelberg, Germany

    Ziya Kaya, Philipp Ehlermann, Renate Oettl & Hugo A. Katus

  3. Department of Cardiology, General Hospital Nuernberg, Paracelsus Medical University, Nuernberg, Germany

    Johannes Schwab

  4. Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany

    Ralf Westenfeld

  5. Department of Internal Medicine III, University Hospital of Saarland, Homburg/Saar, Germany

    Katrin Bachelier

  6. Department of Gynecology and Prenatal Medicine, Hannover Medical School, Hannover, Germany

    Constantin S. von Kaisenberg

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  1. Arash Haghikia
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395_2015_517_MOESM1_ESM.jpg

Supplementary Figure S1: The median time interval between delivery and diagnosis is shown by this graph. This interval did not differ significantly between AAB negative patients and AAB positive patients (JPEG 55 kb)

395_2015_517_MOESM2_ESM.jpg

Supplementary Figure S2: Graph reveals comparison of the baseline LVEF in patients with anti-TnI (A) and anti-Myosin (B) AABs with different titres. Note, that increasing titres were not associated with different levels of LV dysfunction at baseline (JPEG 83 kb)

395_2015_517_MOESM3_ESM.jpg

Supplementary Figure S3: Graph depicts the disease development with regard to the NT-proBNP level stratified by quartiles as compared to the 1st quartile. Note, that neither one quartile showed significantly different rates of patients with cardiac improvement or full recovery (JPEG 69 kb)

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Haghikia, A., Kaya, Z., Schwab, J. et al. Evidence of autoantibodies against cardiac troponin I and sarcomeric myosin in peripartum cardiomyopathy. Basic Res Cardiol 110, 60 (2015). https://doi.org/10.1007/s00395-015-0517-2

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