Induction of cardiomyopathy in severe combined immunodeficiency mice by transfer of lymphocytes from patients with idiopathic dilated cardiomyopathy

Growing evidence suggests that autoimmune mechanisms play an important role in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). The aim of the study was to evaluate the effects of transfer of lymphocytes from pati ents with DCM into severe combined immunodeficiency (SCID) mice on the hear t structure and function. Thirty CB-17 SCID (6-8 weeks old) mice were used and divided into 3 groups (n=10). Mice were injected intraperitoneally with up to 25 x 10(6) peripher al blood lymphocytes (PBL) from either patients with DCM which contain huma n autoantibodies against cardiac beta (1)-adrenegic receptors and M-2-musca rinic receptors (DCM group) or PBL from healthy controls (control-H group). Ten mice did not receive any injections and were used as baseline controls (control-N group). Echocardiography and morphological studies were perform ed seventy five days after the transfer. Results showed that in DCM group, left ventricle dimensions (LVD) in diastole were increased (4.2 +/- 0.1mm) as compared to both control-H group (3.8 +/- 0.1mm) and control-N group (3. 6 +/- 0.1mm) (p < 0.01). Further, there was a trend for increased LVD in sy stole. Fractional shortening was not different between groups. Histological evaluation revealed accumulation of human lymphocytes in the capillaries a nd scarce infiltration of the lymphocytes in the hearts from DCM group. Dif fuse fibrosis was significant increased in DCM mice as compared to mice rec eiving PBL from normal subjects (2.2 +/- 0.3 % vs. 0.8 +/- 0.1 %, p < 0.01) . In conclusion, transfer of the PBL from the patients with DCM was able to induce early stage of heart dilatation in SCID mice. These data provide fo r the first time the direct evidence supporting that the autoimmune mechani sm is important in the pathogenesis of human DCM.