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A humanized HLA-DR4 mouse model for autoimmune myocarditis

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)22-26
JournalJournal of Molecular and Cellular Cardiology
Volume107
Early online date18 Apr 2017
DOIs
DateAccepted/In press - 17 Apr 2017
DateE-pub ahead of print - 18 Apr 2017
DatePublished (current) - Jun 2017

Abstract

Abstract Myocarditis, the principal cause of dilated cardiomyopathy and heart failure in young adults, is associated with autoimmunity to human cardiac α-myosin (hCAM) and the DR4 allele of human major histocompatibility II (MHCII). We developed an hCAM-induced myocarditis model in human HLA-DR4 transgenic mice that lack all mouse MHCII genes, demonstrating that immunization for 3 weeks significantly increased splenic T-cell proliferative responses and titres of IgG1 and IgG2c antibodies, abolished weight gain, provoked cardiac inflammation and significantly impaired cardiac output and fractional shortening, by echocardiography, compared to adjuvant-injected mice. Neither cardiac dilatation nor fibrosis occurred at this time point but prolonging the experiment was associated with mortality. Treatment with mixtures of hCAM derived peptides predicted to have high affinity for DR4 significantly preserved ejection fraction and fractional shortening. Our new humanized mouse model of autoimmune cardiomyopathy should be useful to refine hCAM-derived peptide treatment.

    Research areas

  • Autoimmunity, Myocarditis, Cardiomyopathy, Heart failure

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via ELSEVIER at http://www.sciencedirect.com/science/article/pii/S0022282817300664#!. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 136 KB, PDF document

    Licence: CC BY

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