Elevated myeloid: plasmacytoid dendritic cell ratio associates with early acute cellular rejection in pediatric small bowel transplantation.
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.
Gupta
Ankit
A
Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Ashokkumar
Chethan
C
Ningappa
Mylarappa
M
Sun
Qing
Q
Higgs
Brandon W
BW
Snyder
Sara
S
Johnson
Matthew
M
Zeevi
Adriana
A
Abu-Elmagd
Kareem M
KM
Thomson
Angus W
AW
Mazariegos
George V
GV
Sindhi
Rakesh
R
D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007223:Infant; D007421:Intestine, Small / Q000637:transplantation*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
D015703:Antigens, CD; D039521:CD11c Antigen; D006684:HLA-DR Antigens