Immunoglobulin G3 cardiac myosin autoantibodies correlate with left ventricular dysfunction in patients with dilated cardiomyopathy: immunoglobulin G3 and clinical correlates.
BACKGROUND
Effector functions of an aberrant immune response have been implicated in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). The immunologic determinants of myocardial dysfunction, however, remain poorly understood. This study sought to determine the relation of different immunologic responses to hemodynamic dysfunction in DCM.


METHODS
Immunoglobulin (Ig) G class/subclass response ELISA (enzyme-linked immunosorbent assay) against cardiac myosin heavy chain, histologic characteristics (DALLAS criteria), immunohistochemistry, plasma interleukin-4 and plasma interferon gamma (IFN-gamma) were determined in patients (n = 76) with clinically suspected myocarditis or DCM. Patients were prospectively evaluated, both clinically and hemodynamically, on admission (baseline) and at 6-month follow-up.


RESULTS
Indices of hemodynamic dysfunction (by cardiac catheterization and transthoracic echocardiography) correlated significantly with an Ig subclass response. IgG3 levels correlated with left ventricular ejection fraction (P =.02), pulmonary capillary wedge pressure (P <.0001), left ventricular end-systolic volume index (P =.002), left ventricular end-diastolic volume index (P =.033), left ventricular end-diastolic pressure (P =.04), right ventricular end-diastolic pressure (P =.039), and left ventricular end-systolic dimension and left ventricular end-diastolic dimension (P <.05). Patients positive for IgG3 (predominantly male, P =.01) had depressed left ventricular ejection fraction (< or =45%, relative risk 3.0, 95% CI 1.5-5.7, P =.005) at baseline and 6 months. Mitral-septal separation at follow-up improved in patients negative for IgG3 (P =.018), and the number of patients on conventional therapy in this group declined at 6-month follow-up (P <.05). Lymphocyte counts/high-power field; CD2, CD3, CD4, and CD8 (independent of IgG class/subclass response and left ventricular dysfunction) were significantly higher in patients positive for IFN-gamma (25%). A positive IFN-gamma response was higher in patients positive for IgG3. These patients, positive for IgG3 and IFN-gamma (10%), had significantly shorter duration of clinical symptoms: 0.17 years (0.12-2.36 y) versus 1.01 years (0.49-5.35 y, P =.04).


CONCLUSIONS
IgG3 reactivity correlated with depressed myocardial dysfunction. This may render this subclass Ig a surrogate target for therapeutic intervention in DCM. With IFN-gamma, IgG3 may reflect a more aggressive disease.
Warraich
Rahat S
RS
Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College School of Medicine, Royal Brompton and Harefield Trust, Harefield Hospital, Middlesex, UK. r.warraich@ic.ac.uk
Noutsias
Michel
M
Kazak
Ilkay
I
Seeberg
Bettina
B
Dunn
Micheal J
MJ
Schultheiss
Heinz-Peter
HP
Yacoub
Magdi H
MH
Kuhl
Uwe
U
Kasac
Ilkay
I
D000328:Adult; D015551:Autoimmunity; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011669:Pulmonary Wedge Pressure; D012737:Sex Factors; D013318:Stroke Volume; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018487:Ventricular Dysfunction, Left / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000502:physiology
D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma