Yalçın Seyhun

Influence of cytokine gene polymorphisms on graft rejection in Turkish patients with renal transplants from living related donors.

BACKGROUND Certain cytokine gene polymorphisms (CGPs) have been shown to be associated with renal transplant rejection episodes or graft outcomes. We sought to evaluate the relationships between gene polymorphisms and acute rejection episodes (RG, n = 19) versus stable graft function (NRG, n = 71) in transplant recipients compared with healthy control subjects (HCG, n = 150). The follow-up time period was 18 months. Using polymerase chain reaction sequence-specific primers with the Heidelberg kit we genotyped 22 single nucleotide polymorphisms distributed across 13 cytokine and cytokine receptor genes. RESULTS Interleukin (IL)-2 TT/GT haplotype was found in 36.8% of RG patients and 6.7% of HCG but not among the NRG (P < .0001; .0007). The IL-2 GG/TT haplotype was observed among 13 NRG and nine HCG patients (P = .007); the IL-2 GG/GG haplotype, 18.7% HCG and 4.2% NRG patients (P = .0033); and the IL-2 TT/TT haplotype, five NRG and eight HCG patients, but none of the RG cohort (P > .05). The transforming-growth factor-beta 1 CG/CC haplotype was noted in 15 NRG (21.1%) and four HCG but no RG patients (P < .0001). The IL-2 +166 GT genotype was detected in 36.8% of RG, 8.5% of NRG, and 14.7% of HCG patients (P = .005, .0244). The IL-2 -330 GG genotype was demonstrated in 32 healthy controls and three nonrejection transplant patients (P = .0007). Significant differences were concluded between NRG and HCG for IL-6 565 AG, IL-1beta -511 TT and +3962 CC/CT/TT genotypes. DISCUSSION We observed significant differences among the frequencies of IL-2 gene polymorphisms among RG and NRG subjects, which agreed with previous clinical, but not in vitro studies.

Impact of HLA on the Underlying Primary Diseases in Turkish Patients with End-Stage Renal Disease

The number of patients with end stage renal disease (ESRD) is increasing faster than the number of renal transplantations performed per year worldwide. Of the primary diseases leading to ESRD, diabetic nephropathy is the leading cause. The purpose of the present study is to investigate the association of HLA with the primary diseases leading to ESRD in Turkish patients. A total of 3230 individuals comprising 587 ESRD patients and 2643 healthy controls were enrolled into the study. Class I HLA-A, -B typing was performed by CDC method, while class II HLA-DRB1 typing was performed by low resolution PCR-SSP. We found a significant negative association between almost all A locus antigens and primary disease groups classified as chronic glomerulonephritis and hypertensive nephrosclerosis (p < 0.05). HLA-B58 and HLA-DRB1*03 significantly correlated with amyloidosis and diabetic nephropathy, respectively. Determination of HLAs as risk factors for primary diseases leading to ESRD might be beneficial in preventing progression to ESRD and recurrence of the primary disease post-transplantation.

Relationship Between HLA Tissue Type, CMV Infection, and Acute Graft-vs-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: Single-Center Experience

After allogeneic hematopoietic stem cell transplantation, risk factors for cytomegalovirus (CMV) reactivation include pretransplantation donor and recipient CMV serologic status and posttransplantation development of acute graft-vs-host disease (aGvHD). Human leukocyte antigen (HLA) allele type is an additional factor in CMV infection. The present study included 108 patients who received an allogeneic stem cell graft from an HLA-identical sibling between 1993 and 2004. All recipients and donors were typed for HLA-A, HLA-B, and HLA-DR alleles using serologic or molecular methods. All recipients received grafts because of a hematologic disease from HLA full-matched donors. In pretransplantation seropositive patients with aGvHD, no significant difference was observed in patients who developed CMV infection compared with those without CMV infection. Seropositive patients without aGvHD but with posttransplantation CMV infection demonstrated a higher incidence of HLA-A30, HLA-B40, and HLA-DRB1*15 compared with those without CMV infection. In conclusion, it seems that certain HLA alleles may have either a protective or predisposing role in CMV reactivation, which might be helpful in estimating the risk of aGvHD and designing individualized therapy.

Human leukocyte antigen and major histocompatibility complex class I-related chain A antibodies after kidney transplantation in Turkish renal transplant recipients.

BACKGROUND This study was designed to determine whether human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related A (MICA) antibody (Ab) production during the first 6 months posttransplantation correlated with long-term graft survival and rejection rate. The study group included 147 first transplantations from either living related (LRDs) or deceased donors (DDs) who were divided into two subgroups: rejection (RG, n = 28) and nonrejection (NRG, n = 119). Serum samples (n = 441) collected from each patient on posttransplant days 30, 90, and 180 were tested for HLA and MICA Ab using the Luminex technique. RESULTS Among 82 Ab-positive patients (55.8%), 40 had both HLA and MICA, 33 only HLA, and 9 only MICA Ab in the posttransplant period. The rates of HLA class I, class II, or both Ab positivities were greater in the RG than the NRG (P = .011, .037, and .0275, respectively). At 180 days posttransplant, 64.3% of patients in the RG had Ab and 41.2% in the NRG (P = .0349). The data for the LRD (n = 116) group were similar to those for the entire group; whereas there was no significant difference in Ab positivity between RG and NRG patients who received organs from DDs. There was no significant difference with respect to HLA class II and/or MICA Ab positivity between RG and NRG among patients who lacked HLA class I Ab. DISCUSSION We confirmed that HLA and MICA Ab may be harmful posttransplant, promoting rejection processes and representing an important cause of graft failure. HLA class II and MICA Ab positivities were only important predictors of graft failure when present together with HLA class I positivity. Patients who developed HLA alone or both HLA and MICA Ab rejected their grafts more frequently than Ab-negative recipients.

Anti-HLA antibody profile of Turkish patients with end-stage renal disease.

Exposure to human leukocyte antigens (HLA) via blood transfusions, pregnancies, and previous transplantations can result in anti-HLA antibody production. The presence of anti-HLA antibodies in recipient sera before transplantation is an important risk factor. To demonstrate the anti-HLA antibody status of Turkish end-stage renal disease (ESRD) patients, 674 patients (mean age, 40.35 +/- 13.15 years; female/male, 328/346) were enrolled into the study. Anti-HLA antibody screening and identification tests were performed using an enzyme-linked immunosorbent assay (ELISA) method. The panel-reactive antibody (PRA)-negative group consisted of 564 (83.6%) and the PRA-positive group consisted of 110 (17.3%) patients. Of the 110 (17.3%) PRA-positive patients, 43 (6.4%) were class I (+) and class II (-); 19 (2.8%) were class I (-) and class II (+); 48 (7.1%) were both class I and II (+). The most frequent antibodies were directed against the A2 crossreactive group (CREG) and the A10 CREG with less frequent reactions against the B7 CREG, indicating antibodies to both frequent (members of A2 CREG) and relatively rare (members of A10 CREG and B7 CREG antigens). These data also suggested that some antibodies occur at greater than expected frequency because of shared epitopes. Our findings confirmed the significant correlation between female gender, pregnancy, failed graft history, long dialysis duration, and blood transfusions with PRA positivity (P < .05).

Characterization Of Minor Ha-1 In Patients Who Underwent Living Donor Kidney Transplantation

Amac: Son donem bobrek yetersizligi (SDBY) olan hastalar icin hayat standartlarini arttiran bir tedavi yontemi olan bobrek naklinde HLA uyumunun onemi bilinen bir gercektir. Alici ve verici arasindaki Insan Lokosit Antijenleri (Human Leukocyte Antigens, HLA) uyumunun, allojenik bobrek transplantasyonu sonrasi graft sagkalimi uzerine onemli bir etkisi vardir. Ancak HLA identik kardesler arasi yapilan transplantlar da graft kaybi ile sonlanabilmektedir. Minor histokompatibilite antijenleri (mHag) HA-1, 19. kromozom uzerindeki diallelik genlerce kodlanan, 9 aminoasitlik dusuk polimorfizm gosteren immunojenik bir peptiddir. Minor histokompatibilite antijenleri, HLA uyumlu solid organ transplantasyonlarinin graft rejeksiyonu icin potansiyel bir risk faktorudur. Yaptigimiz bu calismada bobrek transplantasyonunda mHA-1 uyumu veya uyumsuzlugunun, transplant sonrasi graft sagkalimi ile iliskisini arastirmayi amacladik.Hastalar ve Yontemler: Son donem bobrek yetersizligi tanisi konmus 59 hasta ile onlarin akraba vericileri calismaya alindi. Minor HA-1 genotipleri ise PCR-SSP yontemiyle ticari kitler kullanilarak yapildi.Bulgular: 59 hastada HH, RR, HR genotiplerinin sikliklari sirasi ile %17, %25 ve %58 idi. Rejeksiyon/rejeksiyon atagi saptanmasi ile mHA-1 uyumu acisindan anlamli bir fark saptanmadi (p=0.73, Or=1.44, guven araligi=0.36-5.74; Fischer’s Exact Test). Kronik Allograft Nefropatisi (KAN) gelisimi ile mHA-1 uyumu acisindan anlamli bir fark saptanmadi (p=0.61, Or=2.89, guven araligi=0.28-29.57; Fischer’s Exact Test).Sonuc: Yaptigimiz calismada canli donorden bobrek nakillerinde rejeksiyon ile HA-1 uyumsuzlugu arasinda anlamli bir fark saptayamadik