ASSOCIATION BETWEEN CIRCULATING HLA ANTIBODY AND HISTOPATHOLOGIC DIAGNOSIS OF HUMORAL REJECTION.

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ASSOCIATION BETWEEN CIRCULATING HLA ANTIBODY AND HISTOPATHOLOGIC DIAGNOSIS OF HUMORAL REJECTION.
Steven K. Takemoto, PhD , Petros A. Ayele, MD , Brandy T. Oeser , David W. Gjertson, PhD , Michael C. Fishbein, MD , Jon A. Kobashigawa, MD and Elaine F. Reed, PhD . Los Angeles CA, UCLA, 90095, Immunogenetics Center ; Los Angeles CA, UCLA, 90095, Surgical Pathology and Los Angeles CA, UCLA, 90095, Cardiology .

This study examines the incidence of antibody (Ab) and humoral rejection (HR) diagnosis after cardiac transplantation in a large series where immunoflourescence (IF) to diagnose HR in biopsy specimens is routinely performed during the discharge biopsy.
Sera samples for 200 cardiac transplant recipients (mean 11.4 samples per patient, TxYear 1997-2001) were screened by ELISA for antibody reactive to HLA class I and class II antigens. Criteria for transplant coronary artery disease (TCAD) was ≥30% artery occlusion.
PreTx Ab was present in 16%; 10 had +ve T-cell FXM, 16 +ve B-cell FXM, and 6 with DTT T-cell PRA >10%. Denovo Ab was detected in 44%; 23 with class I, 27 with class II, 32 with class I & II, and 4 ELISA -ve with DTT T-cell PRA>10%. Four preTx Ab +ve cases were postTx ELISA -ve.
Of 109 recipients with IF within 6 months, 13 (12%) had HR; 4/12 (33%) with preTx Ab; 7/48 (15%) with denovo and 2/49 (4%) with no detectable Ab (P=0.015); 1/19 with class I, 2/14 with class II and 8/22 (36%) with both I & II Ab (P<0.001). Denovo Ab +ve with both class I & II Ab had highest odds ratio for HR (9.2, 95% CI 1.5-57.7, P=0.02). None/5 B-cell FXM +ve cases had HR. 3-year TCAD-free survival was 96% for Ab –ve, 83% for preTx and 95% for denovo Ab +ve patients (P=0.3).
Of 39 cases with initial IF after 6 months, 8 (21%) had HR; 1/11 had preTx, 5/16 (31%) denovo and 2/12 were Ab -ve. Ab preceded HR diagnosis in 62% (13/21) cases.
Antibody was detected in 60% of cardiac Tx recipients (16% pre, 44% denovo). HR incidence was 12%. Denovo class I & II Ab had highest OR for HR. Three-year followup were insufficient to ascertain an impact of Ab or HR diagnosis on graft outcome.