Document Detail


Congenital heart disease linked to maternal autoimmunity against cardiac myosin.
MedLine Citation:
PMID:  24670798     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.
Authors:
Charles R Cole; Katherine E Yutzey; Anoop K Brar; Lisa S Goessling; Sarah J Van Vickle-Chavez; Madeleine W Cunningham; Pirooz Eghtesady
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2014-03-26
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  192     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-04-21     Completed Date:  2014-06-06     Revised Date:  2014-08-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4074-82     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoantibodies / immunology
Autoimmunity / immunology*
Blotting, Western
Cardiac Myosins / immunology*
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Heart Defects, Congenital / immunology,  pathology
Hypoplastic Left Heart Syndrome / immunology*,  pathology
Immunohistochemistry
Rats
Rats, Inbred Lew
Grant Support
ID/Acronym/Agency:
F32-HL103054/HL/NHLBI NIH HHS; R01-HL56267/HL/NHLBI NIH HHS; R21 HL104391/HL/NHLBI NIH HHS; R21-HL104391/HL/NHLBI NIH HHS; R37-HL35280/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies; EC 3.6.1.-/Cardiac Myosins

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