Leukocyte phenotype and function predicts infection risk in renal transplant recipients

Background. The degree to which transplant recipients are immunosuppressed influences their risks of rejection, infection and cancer. Current measures of immune suppression are crude ( clinical events) or indirect ( drug exposure). We assessed a direct measure of immune status, leukocyte phenotype and function (LPF, a composite measure of five aspects of peripheral blood leukocyte phenotype and function), as a predictor of infection. Methods. A double-blind, prospective, cohort study was conducted, to determine the burden of infection in stable renal transplant recipients with moderate-severe ( Group I, n = 34) or minimal ( Group II, n 36) impairment of LPF, a composite score of: ( i) CD4 count; ( ii) lymphocyte proliferation in response to phytohaemagglutinin A ( PHA); ( iii) serum Ig concentrations; ( iv) neutrophil phagocytic function; and ( v) reactive oxygen species generation. Subjects completed a 6 month diary and each recorded infection was scored 1 - 4: 1, minor undefined infection ( e. g. URTI); 2, minor, microbiologically defined infection ( e. g. UTI); 3, major defined infection ( requiring hospitalization); 4, opportunistic infection ( e. g. Herpes zoster). Final infection score was the sum of all infective episodes. Subjects were then followed-up for 5 years for outcome measures. Results. Groups were well matched for age, sex, diabetes, serum creatinine, rejection and trough cyclosporin concentrations. Group I ( moderate to severe impairment of LPF) recorded a higher infection score, 2.4 +/- 2.8 vs 1.2 +/- 1.2 for Group II, P = 0.02, due to a higher incidence of moderate to severe infection. This relationship was confirmed by multivariate analysis ( OR 1.83, CI 1.08, 3.11, P = 0.03 per unit increase in infection score). During the 5 year follow-up period they had significantly more episodes of admission to hospital, and twice as many admissions due to infections, but no difference in malignancy, graft or patient outcome. Conclusion. LPF testing prospectively identified a cohort who incurred a higher burden of infection. Further studies are required to determine the predictive value of LPF for acute rejection, infection and cancer, and to determine whether adjustments to therapy on the basis of LPF can lead to improved outcomes.