Cardiac myosin autoantibodies and acute rejection after heart transplantation in patients with dilated cardiomyopathy

Objectives. To determine whether humoral autoimmune responses associated wi th dilated cardiomyopathy (DCM) influence the postoperative clinical course following cardiac transplantation. Methods. ELISA levels of preformed cardiac myosin (CM) autoantibodies (Abs) in patients with a pretransplant diagnosis of dilated cardiomyopathy (DCM) (n=64) and ischemic heart disease (IHD, n 53) were correlated with cardiac rejection, immunosuppression, and the incidence of endocardial infiltrates after transplantation. Results. alpha- and beta-CM autoantibody (IgG and IgM) levels were similar in DCM and IHD patients but were statistically higher than in controls. Dis tribution of preformed (beta-CM) IgM-Abs in patients with and without rejec tion in the first postoperative year differed in the two groups. DCM patien ts rejected earlier P=0.006, and the frequency of rejection at 3 months was statistically higher than in IHD patients. Frequency and reactivity of IgM -Abs in DCM patients with rejection [International Society for Heart and Lu ng Transplant (ISHLT) grade I and above] was 28% compared with 7% in reject ion-free patients, P<0.05. IgM-positive patients had a greater frequency an d severity of rejection episodes and required more immunosuppression. These patients had rejection earlier than Ab-negative patients, P<0.009. There w as no correlation between antibody status and rejection in IHD patients or with IgG in either group. Distribution of IgG subclass differed in the two diseases. DCM patients had significantly higher IgG3 reactivity; 70% of thi s activity was present in patients who developed moderate rejection. IgG3-p ositive patients experienced more frequent rejections, as well as a greater incidence of grade 3A/B rejection as the first episode, than did Ab-negati ve patients (50% vs. 15%), P<0.05. Frequency of endocardial infiltrates was statistically higher in IgG3-positive patients. Conclusion, Proinflammatory characteristics of pre formed IgG3 and IgM anti bodies in DCM: patients may influence the frequency and severity of cardiac rejection after transplantation.