Low-dose oral cholecalciferol is associated with higher numbers of Helios(+) and total Tregs than oral calcitriol in renal allograft recipients: an observational study.
Regulatory T cells (Tregs) are a cornerstone of graft acceptance. High numbers of Tregs are associated with better long-term graft survival. Recently, Vitamin D was suggested as an immunomodulator, in addition to its classical role in calcium metabolism. Vitamin D modulates Tregs and might, thereby, promote graft acceptance and long-term graft survival.



One hundred twenty-three renal allograft recipients attending either Heidelberg nephrology or Giessen internal medicine clinic were enrolled in this cross- sectional study. Sixteen healthy controls were studied in addition. Sixty-nine patients were receiving no vitamin D, 38 calcitriol, and 16 cholecalciferol supplementations. We evaluated whether there was a difference in the absolute numbers of Helios(+), Helios(-), CTLA-4(+), IFNg(+), and total Tregs among the patient groups.



Cholecalciferol supplementation was associated with higher absolute numbers of Helios(+), CTLA-4(+), and total Tregs than calcitriol (p < 0.001, p = 0.004, p = 0.001 respectively). Helios(+) Tregs were also higher in cholecalciferol than no vitamin D supplementation patients (p = 0.001), whereas CTLA-4(+) and total Tregs were similar in both groups (p = NS). Helios(+), Helios(-), CTLA-4(+), IFNg(+), and total Tregs were similar in the cholecalciferol and healthy control groups (p = NS).



Our findings indicate that cholecalciferol, even when administered at low dosages, has a stabilizing effect on Tregs (particularly the Helios + subset), in contrast to calcitriol which showed neither a stabilizing nor a proliferation-inducing effect on the same cell population.
Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany. M_Gaafar1984@hotmail.com.|Nephrology Unit, Internal Medicine Department, Assiut University, Assiut, Egypt. M_Gaafar1984@hotmail.com.
Mostafa G
MG
Aly
Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany.
Karina
K
Trojan
Department of Internal Medicine, University of Giessen, Klinikstrasse 33, D-35385, Giessen, Germany.
Rolf
R
Weimer
Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
Christian
C
Morath
Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany.
Gerhard
G
Opelz
Nephrology Unit, Internal Medicine Department, Assiut University, Assiut, Egypt.
Mohammed A
MA
Tohamy
Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany.
Volker
V
Daniel
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D064591:Allografts / Q000187:drug effects / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage*; D002762:Cholecalciferol / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051740:Ikaros Transcription Factor / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000639:trends; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism*
C111431:IKZF2 protein, human; D051740:Ikaros Transcription Factor; D002762:Cholecalciferol; D002117:Calcitriol
Calcitriol; Cholecalciferol; Renal transplantation; Treg