Evaluation of the relationship between de-novo DSA development and CXCR5+PD-1+CD8+ T cells and PD-1/PD-L1 mRNA expression in kidney transplant recipients.

BACKGROUND AND AIMS: The relationship between the Follicular Cytotoxic T cell subgroup and expression levels of PD1/PD-L1 genes and the development of donor specific antibody (DSA) is unknown. In this study, we aimed to examine CD8+CXCR5+PD-1+ follicular cytotoxic T cell levels and expression levels of PD1/PD-L1 genes in peripheral blood lymphocytes in de-novo DSA positive and negative kidney transplant recipients (KTR). METHODS: In our study, expression of PD-1/ PD-L1 genes by Real-Time Quantitative PCR method and CD8+CXCR5+PD-1+ T cell expression levels by flow cytometric method were obtained from peripheral blood samples. 63 participants were included in the study (de-novo DSA positive recipients (n = 22, group 1), de-novo DSA negative recipients (n = 20, group 2) and healthy control (n = 21, group 3). All patients had negative PRA before kidney transplantation. Expression (%) levels of target cells were evaluated by flow cytometry method. IBM SPSS Statistics for Windows Version 22 and R.3.3.2 software were used to evaluate the data. RESULTS: The demographic data of the groups were similar. PD-1 mRNA expression was higher in de-novo DSA positive KTR than negative (respectively, 1.03 ± .29/.82 ± .15, p: .001). CD8+CXCR5+PD-1+ T cell expression levels were found to be higher in the de-novo DSA positive group than in the negative group and similar to the healthy group (respectively, 3.06 ± 1.98/.52 ± .40, p:.001, 3.06 ± 1.98/2.78 ± .59, p:.62). The percentage of CD8+CXCR5+PD-1+ expressing T cells was significantly lower in the HLA-Class II+ group than other groups (HLA CI/II/ I+II, respectively, 3.63 ± 2.72/1.65 ± .50/3.68 ± 1.67, p: .04). CONCLUSIONS: In our study, a significant relationship was found between DSA formation and PD-1 mRNA level and CD8+CXCR5+PD-1+ follicular cytotoxic T cell in KTR.

Relationship of HLA-B alleles on susceptibility to and protection from HIV infection in Turkish population.

OBJECTIVE: Many human leukocyte antigen (HLA)-B alleles are associated with an increased risk of Acquired Immune Deficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) progression; however, their distribution varies among different racial/ethnic groups. Abacavir used in the treatment of AIDS significantly increases the risk of hypersensitivity reactions in patients with HLA-B*57:01. The aim of this study was to determine the distribution of HIV-associated HLA-B subgroups (high and low resolution) and HLA-B*57:01 associated with Abacavir sensitivity in Turkiye. METHODS: This retrospective case-control study consisted of 416 (F/M:111/305) HIV positive patients and 416 (F/M:111/305) healthy controls. HLA-B alleles were identified using Luminex based low-resolution method and further subgrouped by sequence-based high-resolution typing. RESULTS: Our data showed that in patients with HIV-1 infection, HLA-B*15, *35, and *51 allele frequencies were higher, while the HLA-B*07, *14 and *55 allele frequencies were lower as compared to the controls. It was determined that HLA-B*15:01, *35:01, *35:08, and *51:01 alleles frequencies were higher in the patients with HIV-1 infection compared to the controls as HLA-B*07:02, *14:01, *44:01, and *55:01 allele frequencies were detected low. HLA-B*57:01 allele positivity, which is important in Abacavir hypersensitivity, was lower than controls, and this difference was not statistically significant. CONCLUSION: Our results suggest that, HLA-B*07, *14, and *55 alleles and HLA-B*07:02, *14:01, *44:01, and *55:01 subgroups might have a protective effect, while HLA-B*15, *35, and *51 alleles and HLA-B*15:01, *35:01, *35:08, and *51:01 subgroups might play a role in susceptibility to HIV-1 infection.

The relationship between COVID-19 and HLA in kidney transplant recipients, an evaluation of predictive and prognostic factors.

INTRODUCTION: The purpose of this study was to determine the predictive and prognostic factors for COVID-19 infection and its relationship with human leukocyte antigen (HLA) in kidney transplant recipients. MATERIAL AND METHOD: Three hundred fifty kidney transplant recipients were included in the study. Recipients were divided into two groups: COVID-19(+) (n = 100) and control (n = 250). The relationships between HLA frequencies, COVID-19 infection, and prognostic factors (age, donor type, immunosuppression protocol, etc.) were then evaluated. Logistic regression analysis, heatmap, and decision tree methods were used to determine predictive and prognostic factors. The study was performed retrospectively. RESULTS: Advanced age and deceased transplantation emerged as predictive of SARS-CoV-2 infection, while the presence of HLA-A*11, the HLA match ratio, and high-dose tacrolimus were identified as prognostic factors in kidney transplant recipients. HLA-A10, HLA-B*13, HLA-B22, and HLA-B*55 were shown to be associated with SARS-CoV-2 infection at univariate analysis, and HLA-B*57, HLA-DRB1*11, and HLA-DRB1*13 at logistic regression analysis. CONCLUSION: HLA-A10, HLA-B*13, HLA-B*55, HLA-B*57, HLA-DRB1*11, and HLA-DRB1*13 were identified for the first time in the literature associated with SARS-CoV-2 infection in kidney transplant recipients.

New markers for predictions of acute and chronic rejection and graft outcomes in kidney transplant recipients; HLA-G gene 3'UTR 14 bp polymorphism and sHLA-G.

The aim of this study was to evaluate the relation of Human Leukocyte Antigen-G (HLA-G) 14 bp ins/del (insertion/deletion) polymorphism and soluble HLA-G (sHLA-G) level with rejection in kidney transplant recipients. The study was planned as a case-control study involving two hundred fifty kidney transplant recipients. The case group consisted of 125 (female/male: 56/69) kidney transplant recipients diagnosed with acute (n = 52) and chronic rejection (n = 73). The control group consisted of one hundred twenty-five kidney transplant patients with no acute or chronic rejection matched by gender and age in the case group. The sHLA-G level in the recipient's plasma (at the time of rejection for the case, the same time as the case after the transplant for control) was analyzed by Enzyme-Linked Immunosorbent Assay (ELISA). HLA-G 3' untranslated region (3'UTR) polymorphism of recipient and donor was determined using agarose gel electrophoresis and DNA sequencing method. In our study, it was shown that acute rejection rate increased 1.06 times and chronic rejection rate increased 1.14 times in kidney transplant recipients with low serum sHLA-G levels. The rejection patients with the HLA-G 14 bp del/del genotype had higher sHLA-G levels post-transplantation. The frequency of acute rejection was lower in patients with HLA-G 14 bp del/del polymorphism than those with ins/ins and ins/del polymorphisms. This study proposes that HLA-G 3'UTR polymorphism and sHLA-G level might be useful in prediction of rejection in kidney transplant recipients.

Associations between cytokine gene polymorphisms and rheumatoid arthritis in Turkish population.

OBJECTIVE: Various cytokine polymorphisms have been associated with genetic risk factors predisposing to Rheumatoid Arthritis (RA) in different populations. To predict the clinical outcome as well as response to therapy in RA, studies aimed to describe genetic markers. The present study aims to search for polymorphisms of 13 cytokine coding genes in the Eastern Black Sea Region of Turkey. METHODS: DNAs of 49 patients and 96 healthy bone marrow and kidney donors were isolated from peripheral blood samples. Genotyping was performed using the Heidelberg Cytokine Typing Tray kit. PCR products were visualized on an agarose gel, and results were analyzed using the interpretation scheme provided with the kit. Arlequin 3.5 software was used for statistical analysis. RESULTS: No positive association was found between allele frequencies and the disease. However, a negative association was found for the IL-A -889 C allele (p=0.02, OR=0.533, Wald's 95% CI=0.318-0.893). IL-12 -1188 CC (p=0.01, OR=3.667, Wald's 95% CI=1.246-10.786), IL-4 -1098 GT (p=0.02, OR=2.405, Wald's 95% CI=1.129-5.125) genotypes were found positively associated with the RA, while IL-4 -590 CT (p=0.02, OR=0.422, Wald's 95% CI=0.201-0.886) was found negatively associated with the disease. In addition, IL-6 GG haplotype was found positively associated with the RA (p=0.02, OR=1.880, Wald's 95% CI=1.086-3.254). CONCLUSION: Our findings suggest that some polymorphisms of the IL-1A, IL-2, IL-4, IL-6 and IL-12 could be responsible for the susceptibility or protective to RA in our study population. Multi-centered and large numbers of subjects containing studies that search for cytokine polymorphisms will gather more information regarding the susceptibility to RA of Turkish patients.

Tacrolimus Variability: A Cause of Donor-Specific Anti-HLA Antibody Formation in Children.

BACKGROUND AND OBJECTIVES: The most important determinant of long-term graft survival in renal transplantation is adequate immunosuppression. Inadequate immunosuppression may lead to graft loss due to the presence of anti-HLA antibody. The aim of this study was to investigate the effect of variability in tacrolimus blood concentration on anti-HLA antibody development in pediatric recipients of living-donor renal transplants. METHODS: Pediatric recipients of living-donor renal transplants were retrospectively evaluated. Patients with a minimum of two years of follow-up who were administered tacrolimus were included in the study. Patients who had pretransplant anti-HLA antibody were excluded. Variability in tacrolimus blood concentration was assessed using the coefficient of variation ("tacrolimus CV") method. Tacrolimus CV was calculated separately for the first 6 months post-transplant, between 6 and 12 months post-transplant, and from the end of the first year post-transplant to the last follow-up. We constructed receiver operating characteristic (ROC) curves of the tacrolimus CV for each group to find the best cutoff value. RESULTS: A total of 67 patients (including 48 males; 72%) with a mean age of 15.16 ± 4.43 years were included in the study. Anti-HLA antibody positivity was detected in 12 patients (18%). More than three HLA mismatches and the presence of acute cellular rejection correlated with the development of anti-HLA antibody (p = 0.056, 0.009). Tacrolimus CVs for the three periods were 0.37 ± 0.11, 0.31 ± 0.18, and 0.35 ± 0.12, respectively. The cutoff value of tacrolimus CV for anti-HLA antibody development was calculated as 0.32 with a sensitivity of 90.91% and specificity of 50.94% [AUC (area under the curve) 0.713, p = 0.023]. During the second 6-month period and after a  year post-transplant, the percentage of patients with tacrolimus CV > 0.32 was significantly higher in the anti-HLA antibody positive group than in the antibody negative group (67% vs 31%, p = 0.027; 83% vs 47%, p = 0.033). The eGFR (estimated glomerular filtration rate) was similar for the anti-HLA antibody negative and positive groups (78.72 ± 2.86 vs 77.45 ± 8.08, p > 0.05). CONCLUSION: High tacrolimus concentration variability appears to be associated with anti-HLA antibody formation in pediatric recipients of living-donor renal transplants.

Investigation of Human Papillomavirus (HPV) and Epstein-Barr Virus (EBV) in antrochoanal polyps.

OBJECTIVES/HYPOTHESES: This study aimed to investigate the presence of HPV (HPV types 11 and 16) and EBV in antrochoanal polyps and to contribute to the current literature in this regard. STUDY DESIGN: A case-control study. METHODS: A total of 100 patients (including 43 patients undergoing surgery for antrochoanal polyp, 27 patients undergoing surgery for nasal polyp, and 30 patients undergoing surgery for hypertrophic inferior turbinate) were included in this study. DNA was isolated from formalin-fixed, paraffin-embedded samples with the aid of the Bioneer's AccuPrep Genomic DNA Extraction Kit. In the obtained genomic DNAs, while the detection of HPV DNA was performed using the nested-PCR method, the detection of HPV types 11/16 and EBV DNA was performed using the RT-PCR method. RESULTS: The mean age of the patients with antrochoanal polyp was 26.7 ±â€¯15.4 years (range 7-70). There were 20 (46.5%) women and 23 (53.5%) men in the antrochoanal polyp group. HPV DNA was positively detected using the nested-PCR method in 14 (32.6%) of the patients with antrochoanal polyp and in 3 (11.1%) of the patients with nasal polyp. HPV DNA was not detected in the hypertrophic inferior turbinate group (control group). There was a statistically significant difference between all groups in terms of HPV DNA positivity. In the antrochoanal polyp group, 2 patients had HPV 11 positivity and 12 patients had HPV 16 positivity. In the nasal polyp group, 1 patient had HPV 11 positivity and 2 patients had HPV 16 positivity. EBV DNA was positively detected in 16 (37.2%) of the patients with antrochoanal polyp, in 11 (40.7%) of the patients with nasal polyp and in 8 (26.7%) of the patients with hypertrophic inferior turbinate, respectively. There was no statistically significant difference between the groups in terms of EBV DNA positivity. CONCLUSIONS: This study demonstrates that there is a need for further studies investigating the presence of viruses in antrochoanal polyps.

The associations of HLA-A, -B, DRB1 alleles and haplotypes in Turkish lymphoma patients.

A significant association between lymphomas and HLA alleles has been shown in previous studies. However, the frequency of HLA alleles and haplotypes has not been studied in Turkish lymphoma patients. We studied HLA-A, -B, -DRB1 alleles and haplotypes in 80 adult lymphomas and 360 unrelated normal subjects by PCR-SSOP method using Luminex technology. The allele frequencies of HLA-A*29, B*07, and DRB1*11 were higher in patients with Hodgkin's lymphoma (HL) compared with the controls [OR; 5.65 (95%CI; 2.16-14.81), P=0.001], [OR; 3.00 (95%CI; 1.50-5.99), P=0.003)], and [OR; 1.80 (95%CI; 1.08-3.01), P=0.002); respectively]. In patients with non-Hodgkin's lymphoma (NHL) HLA-B*51 and DRB1*04 allele frequencies were higher than controls [OR; 2.25 (95%CI; 1.27-4.00), P=0.007] and [OR; 2.14 (95%CI; 1.20-3.78), P=0.01]. The most frequently observed haplotypes were A*02 B*35 DRB1*11 (7.50% vs. 1.89%) in HL patients, A*02 B*51 DRB1*11 (5.00% vs. 1.96%) in NHL patients, and A*02 B*35 DRB1*13 (2.19%) in the controls. We detected four haplotypes specific to NHL, five haplotypes to HL patients. Seven haplotypes were unique to controls. Our findings suggest that in HL patients, HLA-A*29, B*07, and DRB1*11 alleles, and in NHL patients, HLA-B*51 and DRB1*04 alleles might be presumptive predisposing factors.

Inflammatory cytokine gene polymorphism profiles in Turkish patients with ulcerative colitis.

AIM: To investigate IL-1α, IL-1ß, IL-1R , IL-4RA, TGF-ß, TNF-α and IFN-γ, genes polymorphism in Turkish patients with ucerative colitis (UC). METHODS: An analysis was carried out at Trabzon Karadeniz Technical University Medicine Faculty Gastroenterology polyclinics between March 2005 and May 2011 on 51 patient with UC (cases) and 100 healthy individuals (controls). PCR-SSP and cytokine gene panel (Helderberg kits) based techniques for analysis of gene polymorphisms were used. RESULTS: Changes in allelic frequencies of each of the investigated eight cytokine genes polymorphisms in patient with ulcerative colitis were found. Among the allelic genes analyzed here, the highest statistically significant change was observed in the position TNF-α -308 G/A (339.7%). The following increases were observed in IL-IR mspa T/C variation (179.4%), IFN-γ 5644A/T variation (77.4%), and in IL-1ß -511T/C SNPs (35.9% ). In other analyzed genes, allelic changes were found to be decreasing for TGF- ß codon10C / T (-71.9%), IL4RA + 1902G / A (-47.3 %), and for IL- 1α -889T / C (-37.7%). The lowest negative change (-25.9%) was observed in the allele frequency in IL- 1ß 3962T / C (p les than 0.000). In addition, there were changes in genotypic frequencies investigated seven gene polymophic site and only one of cytokine gene IL-1ß 3962TT/TC/CC was not changed. CONCLUSION: Genes polymorphism is not itself the only determining factor for clinical diagnoses. However, it can be used in the clinical diagnosis of UC in order to determine the low level or high level variations in cytokine gene polymorphisms.

Anti-carbonic anhydrase II antibodies in end-stage renal disease patients.

OBJECTIVE: The aim of this study was to investigate the presence of anti-carbonic anhydrase (CA II) autoantibodies in patients with end-stage renal disease (ESRD) and relationships between the autoantibody titers and ghrelin, glucose, blood urea nitrogen (BUN) and creatinine. SUBJECTS AND METHODS: Serum CA II autoantibody titers, malondialdehyde (MDA), BUN, creatinine and ghrelin levels were measured in 45 ESRD patients and 45 healthy subjects. RESULTS: The CA II autoantibody titers in the ESRD group (0.170 ± 0.237) were significantly higher than those in the control group (0.079 ± 0.032; p = 0.035). MDA and ghrelin levels were also significantly higher in the ESRD group (p < 0.001). A weak positive correlation was determined between anti-CA II antibody titers and MDA, and a negative correlation was observed between ghrelin levels and anti-CA II antibody titers (r = 0.287, p = 0.028 and r = -0.278, p = 0.032, respectively). CONCLUSIONS: In ESRD patients, the results showed the development of an autoimmune response against CA II. This suggests that anti-CA II antibodies could be involved in the pathogenesis of ESRD.

C950T and C1181G osteoprotegerin gene polymorphisms in myeloma bone disease.

OBJECTIVES: Bone disease is one of the hallmarks of multiple myeloma (MM). The role of osteoprotegerin (OPG) in the RANK/RANKL/OPG signaling system is well defined in the myeloma bone disease. Polymorphisms of the TNFRSF11B gene encoding OPG have been studied in various bone diseases. However, relationship between the levels of OPG and development of bone lesions regardless of RANKL is yet unknown. In this study, the effects of OPG gene polymorphism on the development of bone lesions in MM were investigated. METHODS: C950T and C1181G polymorphisms of the OPG gene were studied in 52 MM patients (36 with bone lesions and 16 without bone lesions) and in another 20 control subjects using DNA sequencing. RESULTS: 1181 G and 950 T alleles were overrepresented in MM patients having bone lesions. 950 TT/1181 GG haplotype frequency and TT/GG combined haplotype were also higher in MM patients having bone lesions compared to MM patients without bone lesions or to control. DISCUSSION: This is the first study searching for the relationship between OPG gene variants C950T (promoter), C1181G (exon 1), and myeloma bone disease. It was concluded that the presence of polymorphic 1181 G/950 T alleles and 950 TT/1181 GG genotypes may play a role in the development of bone disease.

Accuracy of HLA-DQ genotyping in combination with IgA anti-tissue transglutaminase serology and a "scoring system" for the diagnosis of celiac disease in Turkish children.

The aim of the study was to analyze the accuracy of (i) HLA-DQ typing and anti-tissue transglutaminase antibodies immunoglobulin A (tTG-IgA) serology and (ii) a "simple scoring system" (SSS) for the diagnosis of celiac disease (CD). The study included 91 patients with positive tTG-IgA, who had been tested for HLA-DQ. Patients were divided into 3 groups: typical CD, atypical CD, and non-CD. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV), positive (PLR) and negative likelihood ratio (NLR) and accuracy of the test combining genotyping and tTG-IgA positivity and the simple scoring system for the diagnosis of CD were evaluated. The combination of genotyping and strong tTG-IgA positivity had a sensitivity of 93.5%, specificity of 61.5%, PPV of 93.5%, NPV of 61.5%, PLR of 2.4, NLR of 0.1 and accuracy of 89% for "CD." SSS had a higher specificity (84.6%), higher PPV (97.3%), higher NPV (68.7%), higher PLR and higher accuracy (92.3%). The combination of genotyping and strong tTG-IgA positivity missed two patients with typical CD (4%) and three patients with atypical CD (10.7%). Two cases with malabsorptive symptoms (33.3%) and three patients without malabsorptive symptoms (42.8%) would have been misdiagnosed as CD if these tests were used. Intestinal biopsy is still mandatory for diagnosis of CD in Turkish children.

Associations of HLA-DRB1 alleles with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in northern east part of Turkey.

AIM: The aim of this study was to investigate the associations between human leukocyte antigen (HLA)-DRB1 alleles with genetic susceptibility to rheumatoid arthritis (RA) and production of antibodies against cyclic citrullinated peptide (anti-CCP antibody) and rheumatoid factor (RF) in Turkish RA patients. METHODS: We studied 291 RA patients and 253 controls. Genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide probes hybridization method. Serum levels of anti-CCP antibody, IgM-RF and high sensitive C-reactive protein titers were measured by commercial kits using immunological methods. RESULTS: We found that HLA-DRB1*04 and *09 alleles were associated in anti-CCP+ and anti-CCP+ RA patients (P < 0.0001 and P < 0.001, respectively), while DRB1*01 and *04 were determined to be higher in RF+ RA patients (P < 0.001 and P < 0.0001, respectively). Moreover, DRB1*11 and DRB1*13 alleles were determined to be lower in RF and anti-CCP/RF+ RA patients (P < 0.001 for both). HLA-DRB1*04 was identified as a common responsible allele for susceptibility to the disease in anti-CCP, RF and anti-CCP/RF- RA patients (P = 0.0018, P = 0.0004 and P = 0.0023, respectively). HLA-DRB1*13 allele alone was found to be protective against to anti-CCP+ and RF- RA (P = 0.0003 and P = 0.006, respectively). On the contrary, there was no protective allele in anti-CCP/RF- RA as well as anti-CCP- RA patients. CONCLUSION: This study indicates that associate and protective HLA-DRB1 allele distributions are different in autoantibody (anti-CCP or RF or anti-CCP/RF)+ RA and autoantibody- RA patients, with exceptions of DRB1*04 and DRB1*13.

HLA-DRB1 allele distribution and its relation to rheumatoid arthritis in eastern Black Sea Turkish population.

Rheumatoid arthritis (RA [MIM 180300]) is a complex, polygenic inflammatory autoimmune disease, resulting from interactions between genetic and environmental factors. Some of the RA-associated HLA-DRB1 alleles have shared epitope, but their distribution varies among different racial/ethnic groups. This study was aimed at investigating the distribution of HLA-DRB1 alleles in patients with RA in eastern Black Sea region of Turkey. DNA samples of 320 patients with RA and 360 healthy controls were studied for the determination of HLA-DRB1 allele distribution using PCR-SSP method. The allele frequencies of HLA-DRB1*01, *04, and *09 were higher in patients with RA compared with the controls (P < 0.005, P < 0.0001, and P < 0.01, respectively). On the other hand, in patients with RA, HLA-DRB1*13 allele was lower than the controls (P < 0.001). Of the HLA-DRB1*04 subgroups, *0401 (40.83% vs. 18.75%, P < 0.001) was the most frequent allele in patients with RA, while DRB1*0402 (30.00% vs. 12.50%, P < 0.005) allele in the controls. HLA-DRB1 allele frequencies in the patients with RA and the controls showed Hardy-Weinberg rule compliance. Results of this study indicate that HLA-DRB1*01, *04, and *09 alleles were associated with RA, and HLA-DRB1*13 was protective allele against RA. Among the subgroups of HLA-DRB1*04, *0401 was detected to be RA associated, while *0402 was being protective. These results have some differences compared with previous reports originating from other regions of Turkey.

Carbonic anhydrase II autoantibody and oxidative stress in rheumatoid arthritis.

OBJECTIVES: To investigate the relationship between carbonic anhydrase (CA) II autoantibody and lipid peroxidation, certain antioxidant parameters, and cytokines in rheumatoid arthritis (RA) patients. DESIGN AND METHODS: Serum levels of CA II autoantibody, cytokines (TNFα, IL-6, IFN-γ, IL-1ß) and bone markers (crosslaps, osteocalcine) and erythrocyte levels of antioxidant enzyme activities (SOD, CAT, GPx), GSH and MDA, and CA activities were measured in RA patients and healthy controls. RESULTS: The CA II autoantibody titers were significantly higher (P<0.05), and erythrocyte SOD activities were significantly lower (P<0.05) in RA patients. A significant negative correlation between CA II autoantibody titers and SOD activities in RA group was established (r=-0.430, p=0.006). The elevated cytokine levels could not be correlated with CA II autoantibody levels in RA. CONCLUSION: These results suggest that increased erythrocyte oxidative stress observed in RA may be effective in the mechanism of CA II autoantibody formation.

Relation of HLA-A, -B, -DRB1 alleles and haplotypes in patients with acute leukemia: a case control study.

BACKGROUND AND AIMS: A relationship between acute leukemia and HLA alleles has been demonstrated in several studies. However, the frequencies of HLA class I (A, B) and class II (DRB1) alleles and haplotypes has not already been determined in Turkish patients with acute leukemia. METHODS: We investigated the relation of the HLA alleles and haplotypes in 237 adult acute leukemia patients [103 acute lymphoblastic leukemia (ALL), 134 acute myeloid leukemia, (AML)] and 360 unrelated normal subjects by PCR-SSOP method using Luminex technology. RESULTS: Allele frequencies of HLA-A*03, and B*51 were higher in patients with AML compared with the controls (p = 0.019, and p = 0.001; respectively). Furthermore, HLA-A*11 and DRB1*01 allele frequencies were determined to be higher in patients with ALL (p = 0.01, p = 0.001; respectively), whereas DRB1*13 allele frequencies lower than controls (p = 0.003). The most observed haplotypes A*03 B*51 DRB1*11 (3.73 vs. 0%) in patients with AML; A*02 B*35 DRB1*01 (2.91 vs. 0%) and A*02 B*51 DRB1*11 (2.91 vs. 1.96%) in patients with ALL were determined. On the contrary, the most observed haplotype was A*02 B*35 DRB1*13 (2.19%) in the controls. We found A*02 B*39 DRB1*16 haplotype negatively associated with AML, whereas A*02 B*35 DRB1*13 was in ALL (p = 0.015, and p = 0.017; respectively). CONCLUSIONS: These results suggest that HLA-A*03 and B*51 alleles may play a presumptive predisposing factor in AML. In addition, HLA-A*11 and DRB*01 alleles have been found to be associated with ALL, whereas DRB1*13 allele was determined to be negatively associated.

MTHFR C677T polymorphism and its relationship to myocardial infarction in the Eastern Black Sea region of Turkey.

BACKGROUND AND AIMS: An association of homozygous MTHFR 677T genotypes with elevated plasma homocysteine level has been documented, but results are still controversial. We aimed to investigate prevalence of the C677T polymorphism in patients with acute myocardial infarction (MI) in the Eastern Black Sea region of Turkey. METHODS: We studied genomic DNA of 231 unrelated patients (aged 59 ± 13 years; 175 male, 56 female) with first anterior acute MI and 242 healthy controls (aged 54 ± 19 years; 182 male, 60 female) using real-time polymerase chain reaction kits for the MTHFR C677T mutation. RESULTS: Prevalence of MTHFR C677T mutant genotype was 49.1% (CT: 45.8%, TT: 3.3%) in controls and 48.45% (CT: 38.5%, TT: 9.95%) in patients with acute MI. The TT mutation was more frequent in patients with acute MI than in controls (9.95 vs. 3.3%) (OR; 3.23, 95% CI; [1.34-8.05], p = 0.003). CONCLUSIONS: The MTHFR gene homozygote TT mutation is a risk factor for patients with MI in the eastern Black Sea Turkish Population.

Treatment related changes in antifibrinolytic activity in patients with polycythemia vera.

Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by predominantly excessive erythrocyte production. During the course of the disease, bleeding or thrombosis may be observed. In PV patients, the influence of antifibrinolytic activities on development of thrombohemorrhagic complications remains to be elucidated. In the present study, alterations in antifibrinolytic activity of PV patients and the effects of treatments on these alterations were investigated. Newly diagnosed and therapy-naive 22 PV patients were included. Thrombomodulin (TM), plasmin-alpha 2-antiplasmin complex (PAP), plasminogen activator inhibitor-1 (PAI-1) and thrombin activable fibrinolysis inhibitor antigen (TAFIa) levels were measured in all individuals and after phlebotomy and 5-hydroxyurea (5-HU) therapy in PV patients. TM, PAP, PAI-1 and TAFIa values of the patient group were higher than those of the controls. After phlebotomy, no changes were detected in TM, PAI-1 and TAFIa values, but PAP values decreased. On the contrary, 5-HU treatment resulted in a marked decrease in TM, PAI-1, PAP and TAFIa levels. These findings suggested that the changes in antifibrinolytic activity and endothelial dysfunction might be contributed to formation of intravascular thrombosis in PV patients, even though not clinically overt. 5-HU in addition to phlebotomy affects antifibrinolytic activity and may have an influence on diminishing predisposition of thrombosis.

Familial Hodgkin's lymphoma from the perspective of HLA.

Although the incidence of Hodgkin lymphoma (HL)--a lymphoid tissue malignity--increases in the presence of several viruses, particularly EBV, as well as with autoimmune diseases and following transplantation, although to date, the exact etiopathogenesis is not known. The higher frequency of HL among family members suggests involvement of genetic factors in its etiology. Studies aiming to elucidate the etiopathogenesis of patients with familial HL (FHL) have reported that human leukocyte antigen (HLA) haplotypes might be involved. In this case presentation, the associations between HLs diagnosed in a father of consanguineous marriage and his two children and HLAs in other family members were investigated and the findings are discussed in view of the published literature; no direct association was found between HLA alleles and the development of the disease in the present case with familial HL.

Prevalence of prothrombotic abnormalities in patients with acute mesenteric ischemia.

Acute mesenteric ischemia (AMI) is a rare condition that may be associated with a variety of congenital prothrombotic disorders (PDs). The purpose of this study was to assess the prevalence of these disorders in 28 AMI patients compared with 103 healthy individuals from the northeastern region of Turkey. They were screened for protein C, antithrombin III, and protein S deficiencies; and gene analysis was performed using the polymerase chain reaction. A PD was revealed in 16 (57%) patients and 33 (32%) controls (p = 0.020). Factor V Leiden (FVL), prothrombin G20210A mutation, and TT677 homozygous mutation of methylenetetrahydrofolate reductase was detected in 10 (36%) patients versus 16 (15%) controls (p = 0.035), 3 (11%) patients versus 10 (9%) controls (p = 1.00), and 1 (3%) patient versus no controls, respectively. Consistent with caucasian ethnic groups, there was high prevalence of PDs, especially FVL; and these abnormalities might be a significant predisposing factor in the pathogenesis of AMI.