HLA-DR incompatibility predicts heart transplant rejection independent of immunosuppressive prophylaxis.
To determine whether immunosuppressive prophylaxis reduces the effect of HLA-DR incompatibility on rejection, we compared clinical and immunologic variables of patients given horse antithymocyte globulin, OKT3, or no immunosuppressive prophylaxis. Median follow-up was 27 months. Groups were similar in race; preoperative HLA reactivity; ABO matching; number of HLA-A, -B, -C, and -DR mismatches; and rejection severity. Patients given immunosuppressive prophylaxis were younger (p = 0.04), had a greater frequency of preoperative ischemic disease (p = 0.03), and had a higher 6-month rejection rate (p = 0.02). A highly significant association was found between the number of mismatches at the HLA-DR locus and rejection severity (p = 0.005). Within the OKT3-based immunosuppressive prophylaxis group and the no immunosuppressive prophylaxis group a significant association was found between the number of HLA-DR mismatches and rejection severity (p = 0.01 and p = 0.009, respectively). A similar trend was identified in the group given horse antithymocyte globulin-based immunosuppressive prophylaxis. Logistic regression, used to identify independent predictors of rejection, showed that the number of HLA-DR mismatches and not the use or type of immunosuppressive prophylaxis is significantly associated with rejection (p = 0.0009). One-year patient survival was 83% in the group with two HLA-DR mismatches and 85% in the group with one or no HLA-DR mismatch. Thus the lower rejection rates in patients with one or no HLA-DR mismatch were not associated with a 1-year survival, which was better than that of patients with two HLA-DR mismatches. The potential benefit of HLA-DR matching on rejection and patient survival must be confirmed by larger prospective studies.
Costanzo-Nordin
M R
MR
Department of Medicine, Loyola University Chicago, Maywood, Ill. 60153.
Fisher
S G
SG
O'Sullivan
E J
EJ
Johnson
M
M
Heroux
A
A
Kao
W
W
Mullen
G M
GM
Radvany
R
R
Robinson
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000627:therapeutic use; D001379:Azathioprine / Q000008:administration & dosage / Q000627:therapeutic use; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000150:complications / Q000503:physiopathology; D005260:Female; D005544:Forecasting; D006084:Graft Rejection / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D006684:HLA-DR Antigens / Q000032:analysis*; D016027:Heart Transplantation / Q000276:immunology* / Q000502:physiology; D006648:Histocompatibility / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000627:therapeutic use; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D015996:Survival Rate
D000961:Antilymphocyte Serum; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone; D008775:Methylprednisolone