Elevated myeloid: plasmacytoid dendritic cell ratio associates with late, but not early, liver rejection in children induced with rabbit anti-human thymocyte globulin.
BACKGROUND
Dendritic cells (DC) play an important role in the induction and regulation of immune responses.


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, cross-sectionally, once, in 48 children, and longitudinally (pretransplant and at days 1-60, 61-200, and 201-400 posttransplant) in 30 children after liver transplantation (LTx). All children received cadaveric (n=53) or live donor (n=25) liver allografts with rabbit anti-human thymocyte globulin induction and steroid-free tacrolimus therapy. Rejectors in both groups were those children (n=35), who experienced biopsy-proven acute cellular rejection (ACR) within 60 days of DC monitoring.


RESULTS
Among rejectors in the longitudinal and cross-sectional cohorts, the MDC:PDC ratio was higher and was associated with decreased PDC frequencies. Logistic regression analysis, leave-one-out cross-validation, and receiver operating characteristic analysis applied to 30 cross-sectional subjects revealed that an MDC:PDC ratio more than or equal to 1.78 was associated with rejector status with sensitivity and specificity of 76.9% and 88.2%, respectively. Sensitivity and specificity were replicated in the 18 remaining cross-sectional subjects (88.8% and 78.8%, respectively), but not in longitudinally monitored subjects, during the early 60-day period after LTx (30.76% and 62.50%, respectively). A significant negative correlation was observed between tacrolimus whole blood concentrations and PDC frequencies (Spearman r=-0.370, P=0.005) in 48 cross-sectional subjects in whom DC subsets were monitored 1 to 3 years after LTx, but not during the early post-LTx period.


CONCLUSIONS
We conclude that an elevated MDC:PDC ratio associates with liver graft rejection, which occurs after first year in children induced with rabbit anti-human thymocyte globulin.
Gupta
Ankit
A
Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15217, USA.
Kumar
Chethan Ashok
CA
Ningappa
Mylarappa
M
Sun
Qing
Q
Higgs
Brandon W
BW
Snyder
Sara
S
Zeevi
Adriana
A
Thomson
Angus W
AW
Mazariegos
George V
GV
Sindhi
Rakesh
R
D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D022423:Myeloid Cells / Q000145:classification / Q000276:immunology / Q000473:pathology; D011817:Rabbits; D012307:Risk Factors; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage; D013997:Time Factors
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016559:Tacrolimus
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