Potential role of autoantibodies belonging to the immunoglobulin G-3 subclass in cardiac dysfunction among patients with dilated cardiomyopathy

Circulation. 2002 Nov 5;106(19):2448-53. doi: 10.1161/01.cir.0000036746.49449.64.

Abstract

Background: Immunoadsorption capable of removing circulating autoantibodies represents an additional therapeutic approach in dilated cardiomyopathy (DCM). The role played by autoantibodies belonging to the immunoglobulin (Ig) subclass G-3 in cardiac dysfunction remains to be elucidated.

Methods and results: Patients with DCM (left ventricular ejection fraction <30%) participated in this case-control study. Nine patients underwent immunoadsorption with protein A (low affinity to IgG-3), and 9 patients were treated with anti-IgG, which removes all IgG subclasses. Immunoadsorption was performed in 4 courses at 1-month intervals until month 3. In the 2 groups, immunoadsorption induced comparable reduction of total IgG (>80%). IgG-3 was effectively eliminated only by anti-IgG adsorption (eg, during the first immunoadsorption course; protein A, -37+/-4%; anti-IgG, -89+/-3%; P<0.001 versus protein A). The beta1-receptor autoantibody was effectively reduced only by anti-IgG (P<0.01 versus protein A). Hemodynamics did not change in the protein A group. In the anti-IgG group during the first immunoadsorption course, cardiac index increased from 2.3+/-0.1 to 3.0+/-0.1 L x min(-1) x m(-2) (P<0.01 versus protein A). After 3 months, before the last immunoadsorption course, cardiac index was 2.2+/-0.1 L x min(-1) x m(-2) in the protein A group and 3.0+/-0.2 L x min(-1) x m(-2) in the anti-IgG group (P<0.01 versus protein A). Left ventricular ejection fraction increased only in the anti-IgG group (P<0.05 versus protein A).

Conclusions: Autoantibodies belonging to IgG-3 may play an important role in cardiac dysfunction of DCM. The removal of antibodies of the IgG-3 subclass may represent an essential mechanism of immunoadsorption in DCM.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Autoantibodies / blood*
  • Autoantibodies / isolation & purification
  • Autoantibodies / pharmacology
  • Calcium Signaling / drug effects
  • Cardiomyopathy, Dilated / complications
  • Cardiomyopathy, Dilated / physiopathology*
  • Cardiomyopathy, Dilated / therapy
  • Case-Control Studies
  • Cells, Cultured
  • Diuretics / therapeutic use
  • Echocardiography
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Immunoglobulin G / blood*
  • Immunoglobulin G / immunology*
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Immunosorbent Techniques
  • Male
  • Middle Aged
  • Myocardial Contraction / drug effects
  • Nitrates / therapeutic use
  • Protein Binding / immunology
  • Rats
  • Receptors, Adrenergic, beta-1 / immunology
  • Stroke Volume / drug effects
  • Treatment Outcome
  • Ventricular Dysfunction, Left / complications
  • Ventricular Dysfunction, Left / physiopathology*
  • Ventricular Dysfunction, Left / therapy

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Autoantibodies
  • Diuretics
  • Immunoglobulin G
  • Immunoglobulin M
  • Nitrates
  • Receptors, Adrenergic, beta-1