title: Peripheral Treg count and it's determinants in unsensitized and sensitized chronic kidney disease patients.
abstract: OBJECTIVE
  Sensitization to HLA antigens resulting in anti-HLA antibodies (panel reactive antibodies; PRA) is a major problem in chronic kidney disease (CKD) patients awaiting transplantation. Induction of anti-HLA antibodies normally occurs through blood transfusion, pregnancy and prior transplantation. However, some patients develop these antibodies for unknown immunological reasons. It is hypothesized that deviations in immune regulation may account for PRA positivity in these patients. We, therefore, investigated whether a quantitative deficiency in peripheral natural regulatory T cells (CD4(+)CD25(high)Foxp3(+); nTreg) plays a role in this phenomenon.
  
  
  METHODS
  Peripheral blood mononuclear cells from 14 patients with positive (Class I and Class II; 10-100 %) and 25 patients with negative PRA, who had not previously been sensitized by blood transfusion, pregnancy and prior transplantation and who had not received any immunomodulatory treatment within the last year, were analyzed for absolute lymphocyte and nTreg numbers through flow cytometry. Samples from 10 healthy people were also used as control.
  
  
  RESULTS
  Mean absolute nTreg numbers were determined to be severely reduced in CKD patients (12 ± 9; n = 39) compared with healthy individuals (53 ± 17; n = 10) (p = 0.008). However, absolute nTreg numbers were similar between PRA- (12 ± 11) and PRA+ (11 ± 8) groups. Interestingly, there was a moderate correlation between the nTreg numbers and HLADR2 genotype (n = 9, r = 0.508, p < 0.05).
  
  
  CONCLUSIONS
  This is the first study to demonstrate that the quantitative peripheral nTreg deficiency in CKD patients does not show a causal relationship with the presence of anti-HLA antibodies.
authors.affiliation: Department of Internal Medicine, School of Medicine, Akdeniz University, Antalya, Turkey.
authors.forename: Cansu
authors.initials: C
authors.lastname: Topal
authors.forename: Sadi
authors.initials: S
authors.lastname: Köksoy
authors.forename: Gültekin
authors.initials: G
authors.lastname: Süleymanlar
authors.forename: Gülşen
authors.initials: G
authors.lastname: Yakuboğlu
authors.forename: F
authors.initials: F
authors.lastname: Fevzi Ersoy
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000276:immunology*; D015802:HLA-DR2 Antigen / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D015802:HLA-DR2 Antigen