title: Cardiac myosin autoantibodies and acute rejection after heart transplantation in patients with dilated cardiomyopathy.
abstract: OBJECTIVE
  To determine whether humoral autoimmune responses associated with 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. Distribution of preformed (beta-CM) IgM-Abs in patients with and without rejection in the first postoperative year differed in the two groups. DCM patients 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 Lung Transplant (ISHLT) grade I and above] was 28% compared with 7% in rejection-free patients, P<0.05. IgM-positive patients had a greater frequency and severity of rejection episodes and required more immunosuppression. These patients had rejection earlier than Ab-negative patients, P<0.009. There was 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 this activity was present in patients who developed moderate rejection. IgG3-positive patients experienced more frequent rejections, as well as a greater incidence of grade 3A/B rejection as the first episode, than did Ab-negative patients (50% vs. 15%), P<0.05. Frequency of endocardial infiltrates was statistically higher in IgG3-positive patients.
  
  
  CONCLUSIONS
  Proinflammatory characteristics of preformed IgG3 and IgM antibodies in DCM patients may influence the frequency and severity of cardiac rejection after transplantation.
authors.affiliation: Department of Cardiothoracic Surgery and Transplant Medicine, National Heart and Lung Institute of Imperial College School of Medicine, Royal Brompton and Harefield Trust, Harefield Hospital, Middlesex, UK.
authors.forename: R S
authors.initials: RS
authors.lastname: Warraich
authors.forename: A
authors.initials: A
authors.lastname: Pomerance
authors.forename: A
authors.initials: A
authors.lastname: Stanley
authors.forename: N R
authors.initials: NR
authors.lastname: Banner
authors.forename: M J
authors.initials: MJ
authors.lastname: Dunn
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
mesh_terms: D000208:Acute Disease; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D002311:Cardiomyopathy, Dilated / Q000601:surgery*; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000601:surgery; D009206:Myocardium / Q000276:immunology*; D009218:Myosins / Q000276:immunology*; D011184:Postoperative Period; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D001323:Autoantibodies; D009218:Myosins