Cardiac autoantibodies in dilated cardiomyopathy become undetectable with disease progression.

Abstract

Objective-To determine the relation of cardiac autoantibody and disease status in a consecutive series of patients with dilated cardiomyopathy by prospective antibody testing at diagnosis and at follow up.

Prospective Familial Assessment in Dilated Cardiomyopathy

“…Further work on IgG subclass 20 and epitope mapping 21 for the individual antibodies may lead to an improvement in the predictability of the various tests. [13][14][15][16][17][18][19][20][21][22] In type 1A diabetes mellitus, standardization and quantification of islet cell antibody has been advantageous to refine its PPV, particularly in relation to high-titer antibody conferring additional risk. 3 To date, this is the first study showing that AHAs identify symptom-free relatives at risk of DCM; the follow-up is relatively short, and the study was not initially planned to prospectively test AHAs as disease predictors.…”

“…In type 1 diabetes mellitus, a staging of preclinical disease has been proposed for siblings of affected children based on a combination of the initial number of antibodies and FPIR to intravenous glucose: no prediabetes (no antibodies), early prediabetes (1 antibody specificity, normal FPIR), advanced prediabetes (2 or more antibodies, normal FPIR), and late prediabetes (at least 1 antibody, reduced FPIR). 29 By analogy, if the same applies to DCM, the staging could be as follows: no pre-DCM (negative AHAs, normal echocardiogram), early (positive AHAs, normal echocardiogram), advanced (AHA-positive and positivity for 1 or more of the other antibodies described in DCM [13][14][15][16][17][18][19][20][21][22] ), and late pre-DCM (at least 1 antibody marker and LVE or dFS). Although 98% of relatives with negative AHAs and AHA is a predictor in the entire cohort (AHA-positive or -negative probands).…”

“…7,22 The frequency of AHAs in healthy relatives of DCM patients was compared with that observed in our established control groups of noninflammatory heart disease (nϭ160, 80 males, age 37Ϯ17 years, of whom 55 had rheumatic heart disease, 67 had hypertrophic cardiomyopathy, and 38 had congenital defects), ischemic heart disease (nϭ141, 131 males, age 44Ϯ14 years), and normal subjects (nϭ270, 123 males, age 35Ϯ11). 7,13,22 Forty-one of the 141 ischemic patients (age 47Ϯ12 years, 28 males; 31 in New York Heart Association class III and 10 in class IV) had suffered a documented myocardial infarction 6 months to 10 years (median 2 years) previously; ejection fraction ranged from 16% to 44% (mean 30Ϯ7%). 7 …”

“…15,16 Although myosin is one of the relevant antigens responsible for the AHAs detected by indirect immunofluorescence, Western blotting, or ELISA in DCM, it is unknown whether subjects classified as seronegative for 1 antibody are positive for another, which is the temporal sequence of appearance of the various antibodies (antimyosin, troponin, ␤-adrenoceptor, mitochondrial, and other antigens) and whether single or multiple antigen-specific antibody tests will be superior to a non-antigen-specific technique such as indirect immunofluorescence as screening tools. [13][14][15][16][17][18][19][20][21][22] Collaborative work among laboratories testing the individual antibodies is warranted. Further work on IgG subclass 20 and epitope mapping 21 for the individual antibodies may lead to an improvement in the predictability of the various tests.…”

“…7,8 -10 Circulating autoantibodies to distinct cardiac autoantigens, including ␣-and ␤-myosin heavy chain, are found in animal models 11,12 and in humans, [13][14][15][16][17][18][19][20][21][22] which represent autoimmune markers in a subset of patients. 1,[7][8][9]13 With indirect immunofluorescence, organ-and disease-specific anti-heart autoantibodies (AHAs) are found in Ϸ30% of DCM patients at clinical presentation 22 and in 20% to 30% of their symptomfree relatives. 7 We have reported that symptom-free relatives of DCM patients with subtle echocardiographic changes, in particular, left ventricular enlargement (LVE) or depressed fractional shortening (dFS) at baseline, have increased medium-term risk for DCM development.…”