Significance of intragraft CD138+ lymphocytes and p-S6RP in pediatric kidney transplant biopsies.
BACKGROUND
We have previously shown that intragraft CD20+ B cells are associated with acute cellular rejection (ACR) and allograft loss. Phosphorylation of S6 ribosomal protein, a downstream target of the PI3K/Akt/mTOR pathway, promotes growth and proliferation of cells and could identify metabolically active cells such as alloantibody secreting plasma cells. Because CD20+ lymphocytes can differentiate into CD138+ plasma cells, we aimed to identify functionally active plasma cells by using intragraft CD138 quantification and p-S6RP staining and correlate these results with allograft rejection, function, and survival.


METHODS
We examined 46 renal transplant biopsies from 32 pediatric patients who were biopsied for clinical suspicion of rejection. Immunohistochemical staining for C4d, CD20, CD138, and p-S6RP was performed. Patient creatinine clearance and graft status was followed up postbiopsy.


RESULTS
Patients with greater than or equal to six CD138+ cells/high power field (hpf) had worse graft survival with a hazard ratio of 3.4 (95% CI 1.3-9.2) 2 years postbiopsy compared with those with 0 to 5 cells/hpf (P=0.016). CD138+ cells were stained for p-S6RP, indicating functionally active plasma cells. They were associated with ACR (P=0.004) and deteriorating graft function (R=0.22, P=0.001). Intragraft CD20+ and CD138+ cells found together in ACR were associated with poorer graft survival than either marker alone, hazard ratio 1.5 (95% CI 1.1-2.2, P=0.01).


CONCLUSIONS
A threshold of greater than or equal to six CD138+ metabolically active plasma cells per hpf, coexisting with CD20+ B cells, was associated with poor allograft function and survival. This may represent an additional antibody-mediated process present in the setting of ACR and could play an important role in characterization and treatment of transplant rejection.
Tsai
Eileen W
EW
Mattel Children's Hospital UCLA, Division of Pediatric Nephrology, Los Angeles, CA, USA. etsai@mednet.ucla.edu
Wallace
William D
WD
Gjertson
David W
DW
Reed
Elaine F
EF
Ettenger
Robert B
RB
D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis; D018951:Antigens, CD20 / Q000032:analysis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001706:Biopsy; D002102:Cadaver; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000276:immunology / Q000502:physiology; D006801:Humans; D007432:Intraoperative Period; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D019520:Living Donors; D008297:Male; D012189:Retrospective Studies; D053668:Syndecan-1 / Q000032:analysis* / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology; D055815:Young Adult
D015703:Antigens, CD; D018951:Antigens, CD20; D053668:Syndecan-1; D003404:Creatinine