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  • Title: Elevated myeloid: plasmacytoid dendritic cell ratio associates with early acute cellular rejection in pediatric small bowel transplantation.
    Author: Gupta A, Ashokkumar C, Ningappa M, Sun Q, Higgs BW, Snyder S, Johnson M, Zeevi A, Abu-Elmagd KM, Thomson AW, Mazariegos GV, Sindhi R.
    Journal: Transplantation; 2010 Jan 15; 89(1):55-60. PubMed ID: 20061919.
    Abstract:
    BACKGROUND: Acute cellular rejection affects more than 60% of children after small bowel transplantation (SBTx). Dendritic cells (DCs) are potent antigen-presenting cells, modulate immune responses to gut microbes, and may serve as markers of rejection-prone small bowel transplantation (SBTx). METHODS: Myeloid CD11c DC (MDC), which may have inflammatory functions, and plasmacytoid CD123 DC (PDC), which may have tolerogenic potential, were measured by flow cytometric analysis, longitudinally (pretransplant, and at days 1 to 60, 61 to 200 posttransplant) in 23 children after SBTx. All children received cadaveric allografts with rabbit anti-human thymocyte globulin induction and steroid-free tacrolimus maintenance therapy. Rejectors were those children (n=16), who experienced biopsy-proven acute cellular rejection within 60 days of SBTx. RESULTS: Of 69 maximum possible observations, 62 were available for analysis. Among rejectors, a significantly higher MDC:PDC ratio (P=0.004) was associated with numerically higher MDC counts and significantly lower PDC frequencies (P=0.017) during the 1- to 60-day time period, compared with nonrejectors. Logistic regression analysis, leave-one-out cross-validation, and receiver operating characteristic analysis revealed that MDC:PDC ratio more than or equal to 1.52 was associated with rejector status with sensitivity/specificity of 86/67% during the 1- to 60-day risk period for early SBTx rejection. Repeated measures analysis showed a significantly higher MDC:PDC ratio (P=0.043, F-test) among rejectors, compared with nonrejectors in cumulative data for pre-SBTx and 1- to 60-day time points. No correlation was seen between DC subsets and tacrolimus blood concentration at any time point. CONCLUSIONS: We conclude that an elevated MDC:PDC ratio associates with early small bowel allograft rejection and may, therefore, identify at-risk recipients in the clinic.
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