Document Detail


Myocardial infarction triggers chronic cardiac autoimmunity in type 1 diabetes.
MedLine Citation:
PMID:  22700956     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients with type 1 diabetes (T1D) suffer excessive morbidity and mortality after myocardial infarction (MI) that is not fully explained by the metabolic effects of diabetes. Acute MI is known to trigger a profound innate inflammatory response with influx of mononuclear cells and production of proinflammatory cytokines that are crucial for cardiac repair. We hypothesized that these same pathways might exert "adjuvant effects" and induce pathological responses in autoimmune-prone T1D hosts. Here, we show that experimental MI in nonobese diabetic mice, but not in control C57BL/6 mice, results in a severe post-infarction autoimmune (PIA) syndrome characterized by destructive lymphocytic infiltrates in the myocardium, infarct expansion, sustained cardiac autoantibody production, and T helper type 1 effector cell responses against cardiac (α-)myosin. PIA was prevented by inducing tolerance to α-myosin, demonstrating that immune responses to cardiac myosin are essential for this disease process. Extending these findings to humans, we developed a panel of immunoassays for cardiac autoantibody detection and found autoantibody positivity in 83% post-MI T1D patients. We further identified shared cardiac myosin autoantibody signatures between post-MI T1D patients and nondiabetic patients with myocarditis, which were absent in post-MI type 2 diabetic patients, and confirmed the presence of myocarditis in T1D by cardiac magnetic resonance imaging techniques. These data provide experimental and clinical evidence for a distinct post-MI autoimmune syndrome in T1D. Our findings suggest that PIA may contribute to worsened post-MI outcomes in T1D and highlight a role for antigen-specific immunointervention to selectively block this pathway.
Authors:
Raju V S R K Gottumukkala; HuiJuan Lv; Lizbeth Cornivelli; Amy J Wagers; Raymond Y Kwong; Roderick Bronson; Garrick C Stewart; P Christian Schulze; William Chutkow; Howard A Wolpert; Richard T Lee; Myra A Lipes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science translational medicine     Volume:  4     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-15     Completed Date:  2012-10-19     Revised Date:  2014-01-29    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  138ra80     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoantibodies / immunology
Autoimmunity / immunology*
Diabetes Mellitus, Type 1 / immunology*
Mice
Myocardial Infarction / immunology*
Myocardium / immunology*
Grant Support
ID/Acronym/Agency:
HL077554/HL/NHLBI NIH HHS; P30 DK36836/DK/NIDDK NIH HHS; R01 DK072090/DK/NIDDK NIH HHS; R01 HL091157/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies
Comments/Corrections
Comment In:
Nat Rev Endocrinol. 2012 Sep;8(9):504   [PMID:  22751343 ]

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