CYTOKINE POLYMORPHISM PROFILE IN HEART TRANSPLANT RECIPIENTS WITH HYPOTENSION, ACIDOSIS, AND VASODILATATION (HAV) SYNDROME
J. Chemmalakuzhy, M.R. Costanzo, P. Meyer, C.B. Jakobsen, J Short, W. Piccione , W. Kao, E. Winkel, M. Saltzberg, A. Heroux, J. Parrillo, A.R. Tambur Rush Medical College, Chicago, Illinois, U.S.A.

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HAV syndrome became a prominent early complication post heart transplantation (HT) in recent years. Pathogenesis of this syndrome is yet to be determined. The current study was designed to investigate whether the genetic profile of cytokine secretion can serve as a marker to identify patients at high risk to develop HAV syndrome.

Fifty two HT recipients [age 52 ± 7 yrs, 72% male, 32% African American (AA), ischemia time 200 ± 20 mins, given triple immunosuppression without anti-lymphocyte antibodies] were analyzed into 2 groups: 30 (58%) who developed HAV [SVR < 800 dines/sec/cm-5 + serum bicarbonate < 20 mEq/L] and 22 (42%) who did not. Promoter polymorphism of five cytokine genes was assessed in all patients as well as in 49 healthy controls. Specifically, PCR-SSP typing was performed to identify single nucleotide substitutions at 1-3 sites in the promoter region. Patients were classified as either High or Low producers of TNF-alpha and IL-6; and as High, Intermediate or Low producers of TGF-beta, IFN-gamma and IL-10.

HT recipients with and without HAV were similar in therapy with ACE inhibitors, IV inotropes, and isoproterenol. Minor variations were noted between the two patients groups, however, no statistically significant differences were observed between HT recipients with or without HAV syndrome regarding phenotypic expression of the above mentioned cytokine promoters. The genotypic profile of the individual nucleotide substitutions was also analyzed. The overall make-up of alleles in HAV syndrome patients, HT recipients without HAV syndrome as well as in healthy controls was comparable. Our overall analysis included multiple donor and recipient parameters. Interestingly, multivariate analysis indicated that increased recipient (p=.0004) and donor (p<.04) weight, as well as ischemia time (p=.0015) are independent predictors of HAV and its severity. It is still likely that cytokine levels at the transplantation site contribute to the severity of HAV pathogenesis. Nevertheless, in our study population, development of HAV syndrome could not be attributed to polymorphism in cytokine gene promoters.