Immunohistological Changes in Dilated Cardiomyopathy Induced by Immunoadsorption Therapy and Subsequent Immunoglobulin Substitution

• DOI: 10.1161/01.cir.103.22.2681
• Publication Date: 2012-06-12T00:09:32Z
• Authors: Alexander Staudt; Frank Schäper; Verena Stangl; Andreas Plagemann; Marco Böhm; Kurt Merkel; Gerd Wallukat; Klaus D. Wernecke; Karl Stangl; Gert Baumann; Stephan B. Felix
• Keywords: Cardiomyopathy, Dilated; Male; Time Factors; CD3 Complex; CD8 Antigens; Heart Ventricles; Histocompatibility Antigens Class II; Middle Aged; Immunohistochemistry; 3. Good health; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Immunoglobulin G; CD4 Antigens; Receptors, Adrenergic, beta; Humans; Female; Immunosorbent Techniques; Autoantibodies

Background —Immunoadsorption (IA) and subsequent immunoglobulin (Ig) G substitution represent an additional therapeutic approach in dilated cardiomyopathy (DCM). It remains to be elucidated whether this treatment modulates myocardial inflammation, which is possibly a causal factor of ventricular dysfunction.

Methods and Results —From 25 DCM patients (EF <30%), 12 patients were randomized for IA therapy and subsequent IgG substitution at 1-month intervals until month 3. Before (<7 days) and after IA therapy, right ventricular biopsies were obtained from all patients. Biopsies were also obtained at intervals of 3 months from 13 patients without IA/IgG treatment (controls). IA/IgG treatment induced improvement in left ventricular ejection fraction from 21.3±1.7% (±SEM) to 27.0±1.3% ( P <0.01 versus baseline/controls) and reduction of the β-receptor autoantibody serum levels ( P <0.01 versus baseline/controls). The number of CD3 cells decreased from 5.7±0.8 to 2.9±0.5 cells/mm 2 ( P <0.01 versus baseline/controls). This decline was paralleled by a decrease in CD4 ( P <0.01 versus baseline/controls) and CD8 ( P <0.05 versus baseline/controls) lymphocytes. The number of leukocyte common antigen–positive cells (leukocytes) was reduced from 20.0±3.2 to 9.9±2.8 cells/mm 2 ( P <0.01 versus baseline/ P <0.05 versus controls). HLA class II expression decreased from 2.1±0.7% to 1.1±0.4% ( P <0.05 versus controls/baseline). The number of immunopositive cells and the expression of HLA class II in controls remained stable. In both groups, the degree of fibrosis remained unchanged.

Conclusions —IA and subsequent IgG substitution mitigate myocardial inflammation in DCM.