title: Preformed IgG antibodies against major histocompatibility complex class II antigens are major risk factors for high-grade cellular rejection in recipients of heart transplantation.
abstract: BACKGROUND
  Preformed anti-HLA antibodies reacting specifically with donor lymphocytes have been associated with acute vascular rejection and early cardiac allograft failure. However, the effect of preformed anti-HLA antibodies directed against allogeneic major histocompatibility complex (MHC) class I or II antigens of a donor panel on heart transplantation outcome has not been extensively studied.
  
  
  RESULTS
  The study group consisted of 68 patients who received cardiac transplants between 1989 and 1996 and who were at high risk for developing anti-HLA antibodies before transplantation. The effect of preformed antibodies against allogeneic MHC class I or class II antigens on the development of early high-grade cellular rejection and on cumulative annual rejection frequency was determined. Both patients with left ventricular assist devices and retransplantation candidates had a similar increase in the frequency of IgG anti-MHC class II antibodies (IgG anti-II) compared with control subjects (P<0.0001), whereas the frequency of IgG anti-MHC class I antibodies (IgG anti-I) was elevated only in patients with left ventricular assist devices. Pretransplantation IgG anti-II predicted early development of high-grade cellular rejection (P=0.006) and higher cumulative annual rejection frequency (P<0.001) in both of these sensitized patient groups. Among retransplantation recipients, a match between donors 1 and 2 at HLA-A additionally predicted an earlier time to a high-grade cellular rejection.
  
  
  CONCLUSIONS
  These results emphasize the importance of specifically screening heart transplantation candidates for the presence of IgG antibodies directed against MHC class II molecules and suggest that strategies aimed at their reduction may have an impact on the onset and frequency of high-grade cellular rejections after transplantation.
authors.affiliation: Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Itescu
authors.forename: T C
authors.initials: TC
authors.lastname: Tung
authors.forename: E M
authors.initials: EM
authors.lastname: Burke
authors.forename: A
authors.initials: A
authors.lastname: Weinberg
authors.forename: N
authors.initials: N
authors.lastname: Moazami
authors.forename: J H
authors.initials: JH
authors.lastname: Artrip
authors.forename: N
authors.initials: N
authors.lastname: Suciu-Foca
authors.forename: E A
authors.initials: EA
authors.lastname: Rose
authors.forename: M C
authors.initials: MC
authors.lastname: Oz
authors.forename: R E
authors.initials: RE
authors.lastname: Michler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000937:Antigen-Antibody Reactions; D002874:Chromosome Mapping; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics; D016027:Heart Transplantation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D011300:Preoperative Care / Q000379:methods; D012307:Risk Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D015234:HLA-A Antigens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G