Elevated Myeloid: Plasmacytoid Dendritic Cell Ratio Associates With Early Acute Cellular Rejection in Pediatric Small Bowel Transplantation
ABSTRACT 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).
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.
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.
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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ABSTRACT: Background: In the last years many studies have been designed to predict risk of acute rejection and to adapt the immunosuppressive therapy. The importance of dendritic cells (DCs) in the immune response, especially their role in tolerance is known. Thus, we investigated the influence of tacrolimus (TAC)-based and of cyclosporine A (CsA)-based immunosuppressive therapies on dendritic cells and the incidence of rejection in heart transplant recipients. Methods: Groups consisted of 14 CsA treated and 15 TAC treated patients. At different study time points (0, 3 and 6 months after study begin) peripheral blood from the patients was drawn to analyse (1) blood concentration of CsA or TAC (trough value) and (2) percentages of plasmacytoid and myeloid DC (p and mDC) subsets using flow cytometry. Histological rejection grading was performed of endomyocardial biopsies. Results: TAC treated patients had significantly higher values of pDCs (CsA group 53.9%±13.0%; TAC group 67.5%±8.4%; p<0.05) and significantly lower values of mDCs than CsA treated patients (CsA group 58%±19.0%; TAC group 45.2%±10.7%; p<0.05). In general, HTx patients with rejection grade of ≥2 had significant lower values of pDCs (55.1%±16.2%) compared to patients without rejection (63.6%±10.5%; p<0.05). TAC-treated patients had significantly less rejections CsA-treated patients (CsA group 0.86±0.95; TAC group 0.2±0.4; p<0.05). Conclusions: Our results showed that HTx patients with high pDCs had a lower risk for rejection and that TAC-treated patients had higher pDCs values compared to CsA-treated patients. Future studies need to define individual pDC values to predict acute cellular rejection. © 2014 International Clinical Cytometry Society.Cytometry Part B Clinical Cytometry 09/2014; 86(5). DOI:10.1002/cyto.b.21169 · 2.23 Impact Factor
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ABSTRACT: The incidence of early rejection after intestinal transplantation correlates with heightened risk of graft loss and mortality. Many different induction or pre-conditioning protocols have been reported in the last 10 yr to improve outcomes; however, sepsis remains prevalent and diminishes long-term results. We recently began a "2-dose" alemtuzumab trial protocol - 15 mg at day 0 and 15 mg repeated on day 7 - with the hope of reducing our infection rate. We compared three different protocols used at our institution (daclizumab, conventional "4-dose" alemtuzumab, and "2-dose" alemtuzumab). There was a significantly lower rate of early rejection with the "2-dose" alemtuzumab protocol in our study group of mainly (88%) intestinal grafts without accompanying liver engraftment with its protective immunologic effect. Sepsis remained low. Longer follow-up will be required to evaluate the effects of this new protocol on longer-term outcomes.Clinical Transplantation 07/2013; 27(4). DOI:10.1111/ctr.12166 · 1.49 Impact Factor
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ABSTRACT: One of the most intensively studied holothurians, Holothuria scabra has been discussed in the literature since 1833. The species is important for several reasons: (1) it is abundant and widely distributed in shallow soft-bottom habitats throughout the Indo-Pacific; (2) it has a high value on the Asian markets, where it is mainly sold as beche-de-mer; and (3) it is the only tropical holothurian species that can currently be mass produced in hatcheries. Research on H. scabra continues but because of commercial exploitation, wild stocks are declining. This review compiles data from 14 these and 352 technical reports and scientific papers pertaining to the biology, ecology, aquaculture and fisheries of H. scabra. Although several references are likely to have been missed by our investigation, we present the most complete reference list to date, including obscure material published by local institutions and/or in foreign languages. Our main aim was to summarize and critically discuss the abundant literature on this species, making it more readily accessible to all those wishing to conduct fundamental research, or aquaculture and stock enhancement programmes, on H. scabra across its entire geographic range.Advances in Marine Biology 01/2001; DOI:10.1016/S0065-2881(01)41003-0 · 5.00 Impact Factor