Targeting CD20+ B-lymphocytes in inflammatory dilated cardiomyopathy with rituximab improves clinical course: a case series

Abstract

Background: The aetiology of dilated cardiomyopathy (DCM) is highly heterogeneous including genetic and/or acquired (infective, toxic, immune, endocrine, and nutritional) factors. The major part of acquired DCM in developed countries is caused by either viral or autoimmune myocarditis. It is believed that the activation of the T-lymphocyte cell system is the major pathomechanism underlying autoimmune myocarditis and inflammatory DCM (DCMi). However, in the hearts of a subset of patients, a significant number of CD20+ B-lymphocytes can be detected too. Limited information exists on the role of B-cell-dependent mechanisms in the progression of DCMi. Particularly CD20+ B-lymphocytes, which can be targeted by anti-CD20+ B-lymphocytes antibodies or inhibitors, might contribute to the pathogenesis of myocardial damage beyond antibody production.

Case summary: Here, we present a case series of six patients with subacute and chronic endomyocardial biopsy-proven CD20+ B-lymphocyte-associated DCMi, where symptomatic heart failure therapy, with or without combined immunosuppressive therapy with steroid-based treatment regime, was insufficient to improve cardiac function. Five patients improved clinically several weeks after a standard infusion protocol with rituximab, a chimeric monoclonal antibody against the pan-B-cell surface molecule CD20.

Discussion: Our case series shows that CD20+ B-lymphocyte persistence can play a pathophysiologic role in a subset of DCMi patients and highlights the potential of targeting CD20+ B cells in patients with prominent CD20+ B-lymphocyte persistence.

Keywords: B-lymphocytes; CD20+; Case report; Inflammatory dilated cardiomyopathy; Rituximab.

Figure 1

Pie graph representations of CD20+ B-lymphocytes-association with inflammatory dilated cardiomyopathy. (A) The pie chart represents 82 patients (red) with endomyocardial biopsies CD20+ B-lymphocytes infiltrates (>7 cells/mm²) out of 156 inflammatory dilated cardiomyopathy patients. (B) The main pie chart represents 24 endomyocardial biopsies-proven inflammatory dilated cardiomyopathy patients who were treated with prednisolone/azathioprine for 6 months, 16 patients (blue) were responders and eight patients (yellow) were non-responders. The pie-of-pie represents the steroid non-responders of which five patients (dark red) showed high-persistent endomyocardial biopsies CD20+ B-lymphocyte infiltrates (average 20.8 cells/mm²), and three patients (orange) with newly identified low-grade CD20+ B-lymphocytes in the follow-up biopsies (average 12.50 cells/mm²).

Figure 2

Representative pictures of CD20+ B-lymphocytes (A, C) and CD138+ plasma cells (B, D) infiltrates in paraffin-embedded endomyocardial biopsies of two patients with CD20+ myocarditis, indicating that the CD20 staining pattern differs from that from CD138 staining. Magnification x 200; CD 138: Anti-CD20: monoclonal mouse antibody, clone 8J662 (Fa. Biomol, Hamburg, Germany); Anti-CD138; clone B-A38 (Roche Diagnostics, Mannheim, Germany).