Growing evidence suggests that the autoimmune mechanism plays an important role in the pathogenesis of
dilated cardiomyopathy. The purpose of this study was to evaluate the effect on the cardiac structure and function by the transfer of
immunoglobulin G (
IgG) and/or lymphocytes from rabbits immunized with a synthetic
peptide corresponding to the sequence of the second extracellular loop of beta1-adrenoceptor (beta
peptide) into
severe combined immunodeficiency (SCID) mice. CB-17 SCID mice were injected intraperitoneally with 2 mg of
IgG and/or 1 x 10(7) peripheral blood lymphocytes (PBL) from either rabbits immunized with both beta1
peptide and adjuvant (beta group), and adjuvant or rabbits with adjuvant only (N group). Thirty-five SCID mice were divided into seven groups: (1) N-
IgG group; (2) N-PBL group; (3) N-IgG+PBL group; (4) beta-
IgG group; (5) beta-PBL group; (6) beta-IgG+PBL group; and (7) control group. Morphological, serological and endocrinological studies were performed 70 days after the transfer. Results showed that heart weight and heart
weight/body weight ratio in the beta-IgG+PBL group tended to be increased as compared with those in other groups. All mice in the beta-
IgG group, two in the beta-PBL group and four in the beta-IgG+PBL group showed high titer of rabbit anti-beta1-adrenoceptor
antibodies.
Brain natriuretic peptide in the beta-IgG+PBL group showed a significant increase as compared with those in the control group and N-IgG+PBL. Pathohistologically, focal infiltration of inflammatory cells in the myocardium was observed in one mouse of the beta-IgG+PBL group. Rabbit CD3-positive T-lymphocytes in the myocardium were observed in two mice of the beta group. In conclusion, transfer of
IgG and PBL from rabbits immunized with beta1
peptide was able to induce the early stages of myocardial damage in SCID mice. These data provide direct evidence that the autoimmune mechanism is important in the pathogenesis of
dilated cardiomyopathy.