| Myocardial infarction triggers chronic cardiac autoimmunity in type 1 diabetes. | |
| | |
MedLine Citation:
|
PMID: 22700956 Owner: NLM Status: In-Data-Review |
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 |
Related Documents
:
|
17060106 - Characterization of microvascular dysfunction after acute myocardial infarction by card... 19423956 - The value of 99mtc-mibi myocardial perfusion imaging in differentiation of heart failur... 21651806 - Levosimendan and mortality after coronary revascularisation: a meta-analysis of randomi... 12845246 - Electrocardiographic gated (99m)tc-sestamibi spect immediately after primary percutaneo... 15668826 - Access-site complications after rescue percutaneous coronary intervention during thromb... 2557716 - Radionuclide assessment of right ventricular regional wall motion abnormalities in ante... |
Publication Detail:
|
Type: Journal Article |
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: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101505086 Medline TA: Sci Transl Med Country: United States |
Other Details:
|
Languages: eng Pagination: 138ra80 Citation Subset: IM |
Affiliation:
|
Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus.
Next Document: Successful treatment of ebola virus-infected cynomolgus macaques with monoclonal antibodies.