Impact of HLA polymorphisms on the susceptibility to SARS-CoV-2 infection and related mortality in patients with renal replacement therapy.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection could present in a clinical spectrum of varying severity. Human leukocyte antigen (HLA) is a crucial component of the viral antigen presentation pathway and immune response to the virus. Therefore, we aimed to assess the impact of HLA allele polymorphisms on the susceptibility to SARS-CoV-2 infection and related mortality in Turkish kidney transplant recipients and wait listed patients, along with clinical characteristics of the patients. We analysed data from 401 patients with clinical characteristics according to presence (n = 114, COVID+) or absence of SARS-CoV-2 infection (n = 287, COVID-) who had previously been HLA typed to support transplantation. The incidence of coronavirus disease-19 (COVID-19) was 28 %, and the mortality rate was 19 % in our wait listed/ transplanted patients. Multivariate logistic regression analysis showed that a significant HLA association between HLA- B*49 (OR = 2.57, 95 % CI, 1.13-5.82; p = 0.02) and HLA- DRB1*14 (OR = 2.48, 95 % CI, 1.18-5.20; p = 0.01) with SARS-CoV-2 infection. Besides, in COVID + patients, HLA-C*03 was correlated to mortality (OR = 8.31, 95 % CI, 1.26-54.82; P = 0.03). The new finding from our analysis suggests that HLA polymorphisms could be associated with the occurrence of SARS-CoV-2 infection and COVID-19 mortality in Turkish patients with renal replacement therapy. This study may provide new information for the clinician to identify and manage sub-populations at risk in the setting of the current COVID-19 pandemic.

Impact of medium cut-off membranes on S100A12 and soluble receptor for advanced glycation end products.

INTRODUCTION: Of the most remarkable molecules associated with atherosclerosis and the cardiovascular outcome are S100A12 (10,379.5 Da) and soluble receptor for advanced glycation end products (sRAGE-42,803 Da) in the hemodialysis (HD) population. We designed a study investigating the effects of the medium cut-off (MCO) dialyzers focusing on S100A12 and sRAGE in HD patients compared with low-flux and high-flux dialyzers. METHODS: This single-site, prospective, observational study comprises age and sex-matched HD groups (low-flux, high-flux, and MCO). Blood samples were drawn at baseline (predialysis and postdialysis) and the sixth month (predialysis). RESULTS: Groups had similar demographic features and laboratory parameters. Baseline S100A12 levels of the groups were similar [34.3 (±66.5), 30.9 (±42.7), and 40.6 (±29.6); p = 0.13]. Compared to their baseline, the sixth-month S100A12 levels were constant in low-flux and high-flux group and significantly lower in MCO group (p = 0.16, p = 0.33, and p = 0.004). Baseline sRAGE levels of the groups were similar at baseline [2.8 (±0.8), 2.7 (±0.6), and 2.6 (±0.7); p = 0.65], and the sixth-month [2.9 (±0.5), 2.4 (±0.7), and 2.4 (±0.8); p = 0.24]. sRAGE levels remained constant in all groups [p = 0.84, p = 0.13, and p = 0.39]. S100A12/sRAGE ratio at baseline and sixth month was constant in low-flux [22.3 (±63.7) and 18.1 (±24.8); p = 0.17] and high-flux groups [11.9 (±15.3) and 13.1 (±5.8); p = 0.26], the ratio decreased significantly in MCO group [16.5 (±11.6) to 7.8 (±5.5); p = 0.03]. CONCLUSION: Our study suggests that prolonged use of MCO dialyzers is associated with better S100A12 and sRAGE levels. Long-term studies with larger samples are needed to understand the effects of a better S100A12-sRAGE profile provided by MCO dialyzers on HD patients' cardiovascular outcomes.

Occurrence of familial Mediterranean fever in haemophilia patients.

INTRODUCTION: This is the first study of simultaneous occurrences of Familial Mediterranean Fever (FMF) in patients with haemophilia. AIM: The aim was to investigate the frequency and clinical characteristics of FMF in patients with severe haemophilia. METHODS: Our study included 30 patients with severe haemophilia (26 haemophilia A and four haemophilia B). All 30 patients are screened for MEFV genotypes in FMF according to the new Eurofever/PRINTO diagnostic criteria. All cohorts were genetically tested for FMF and thrombophilia. RESULTS: Eight (26%) of 30 haemophilic patients were diagnosed with FMF. Six different heterozygous FMF mutations including M694V (n = 2), E148Q (n = 2), V726A(n = 1), P369S (n = 1), E148Q/K695R (n = 1) and E148Q/M694I (n = 1) were identified. Seven had haemophilia A and only one had haemophilia B. Four (50%) patients had a positive family history and three of them had extraarticular findings specific to FMF. Only one haemophilia B patient received colchicine. Target joints in the knee, ankle, and elbow were identified in three FMF patients. The number of target joints in eight patients with FMF was significantly lower than in twenty-two patients without FMF (p < .05). The annual number of suspected joint bleedings in FMF patients admitted to the hospital was 40; however, 15 (37.5%) were documented bleedings in ultrasounds. Hereditary thrombophilia was detected in seven of eight patients. CONCLUSION: Our data indicate that screening for FMF may be useful in patients with haemophilia who develop arthritis without prominent bleeding and have a positive family history in many Mediterranean countries, including Turkey.

Does Age at Onset Affect the Clinical Presentation of Familial Mediterranean Fever in Children?

BACKGROUND/OBJECTIVE: The aim of this study was to compare the clinical and demographic features and evaluate the phenotypic and genotypic differences of pediatric familial Mediterranean fever (FMF) patients according to their age at disease onset. METHODS: Records of 854 patients who were diagnosed with FMF between 2006 and 2017 were evaluated. Patients were divided into 2 subgroups according to their age at disease onset. Group 1 comprised FMF patients who had experienced their first attack at 2 years or younger (younger onset), and group 2 comprised FMF patients who had experienced their first attack at older than 2 years. RESULTS: There were 155 patients in group 1 and 699 patients in group 2. Delay in diagnosis, attack frequency, duration of attacks, fever, chest pain, erysipelas-like erythema, incidence of family history, anti-interleukin 1 therapy use, and M694V homozygous and M680I homozygous mutations were significantly higher in group 1, whereas arthralgia and abdominal pain were significantly higher in group 2. There were no significant differences in arthritis, amyloidosis, and protracted febrile myalgia between the groups. The colchicine dose at last visit and Pras activity score were higher in group 1. CONCLUSIONS: It seems that FMF patients with a younger onset has a more severe disease course. They needed higher doses of colchicine to control the attacks. M694V and M680I homozygous mutations presented more frequently in younger-onset FMF patients. Increased awareness of physicians of the early presentation of FMF may prevent delays in FMF diagnosis.

Factors Affecting Bone Health in Kidney Transplant Recipients: Klotho Gene Single-Nucleotide Polymorphisms and Other Clinical Features.

OBJECTIVES: Posttransplant bone diseases are a major cause of morbidity in kidney transplant recipients. We investigated the relationship between klotho gene single-nucleotide polymorphisms and bone diseases after kidney transplant. We also aimed to identify possible risk factors for development of bone disease. MATERIALS AND METHODS: The study consisted of 251 kidney transplant recipients (164 men and 87 women) with minimum follow-up of 3 years after kidney transplant. Patients with prolonged immobilization, malignancy, parathyroidectomy, glomerular filtration rates less than 30 mL/min/1.73 m², hypo- or hyperthyroidism, and treatment with drugs that affect bone metabolism were excluded. We investigated the relationship between 6 single-nucleotide polymorphisms of the klotho gene (rs480780, rs211234, rs576404, rs211235, rs9536314, and rs1207568) and development of osteoporosis, avascular bone necrosis, and persistent hyperparathyroidism. RESULTS: Longer dialysis treatment (odds ratio, 1.13; P = .002) and rs211235 single-nucleotide polymorphism in the klotho gene (odds ratio, 9.87; P = .001 for GG genotype) were significantly associated with persistent hyperparathyroidism. A higher magnesium level was detected as a protective factor from development of persistent hyperparathyroidism (odds ratio, 0.19; P = .009). Persistent hyperparathyroidism was defined as a risk factor for development of osteopenia/osteoporosis (odds ratio, 2.76; P = .003) and avascular bone necrosis (odds ratio, 2.52; P = .03). Although the rs480780 (odds ratio, 8.73; P = .04) single-nucleotide polymorphism in the klotho gene was defined as a risk factor for development of osteopenia/osteoporosis, none of the klotho single-nucleotide polymorphisms was found to be associated with development of avascular bone necrosis. CONCLUSIONS: Persistent hyperparathyroidism could be an important indicator for development of bone disease in kidney transplant recipients. Also, some of the klotho gene single-nucleotide polymorphisms are associated with higher risk for bone disease after kidney transplant.

TCF7L2 (rs7903146) But Not CDKAL1 (rs7754840) Gene Polymorphisms Increase the Risk of New-Onset Diabetes After Kidney Transplant.

OBJECTIVES: Incidence of new-onset diabetes after transplant negatively affects graft and patient survival. Obesity, impaired fasting glucose before transplant, and a history of diabetes in first-degree relatives are well-defined risk factors. TCF7L2 and CDKAL1 gene polymorphisms have been implicated in the pathogenesis. We investigated the effect of single gene polymorp-hisms of TCF7L2 (rs7903146) and CDKAL1 (rs7754840) on new-onset diabetes in renal transplant recipients. MATERIALS AND METHODS: We evaluated 239 renal transplant recipients. TCF7L2 and CDKAL1 gene polymorphisms were assessed by polymerase chain reaction. RESULTS: Mean patient age was 43 ± 13 years. There were 148 male patients (61.9%), and 91 were female (38.1%). New-onset diabetes was detected in 55 patients (23%). In 20 cases (36%), the glycemic disorder was transient; 61% of patients required insulin therapy. In terms of CDKAL1, 108 patients had the wild-type allele, 112 had a single-allele mutation, and 19 had a 2-allele mutation (45.2%, 46.9%, and 7.9%, respectively). In terms of TCF7L2, 163 of the patients had the wild-type allele, 49 had a single-allele mutation, and 27 had a 2-allele mutation (68%, 20%, and 11%, respectively). New-onset diabetes-related factors were age at transplant, body mass index after transplant (calculated as weight in kilograms divided by height in meters squared), tacrolimus, mycophenolate, and TCF7L2 polymorphism but not CDKAL1 polymorphism. After multiple regression analysis, the effect of TCF7L2 polymorphism persisted. A single allelic change resulted in a risk factor 1.4 times higher for new-onset diabetes after transplant (P = .043; 95% CI, 1.142-1.874) and a double allelic change was 2.7 times higher (P < .01; 95% CI, 1.310-4.073) Conclusions: TCF7L2 (rs7903146) gene polymorphism is an independent risk factor for new-onset diabetes in Turkish renal transplant patients. This study is the first in Turkey to show the distribution and effect of these genes in kidney transplant patients.

HLA-Cw6 Status and Treatment Responses Between Psoriasis Patients.

Background: The number of treatment options in psoriasis has increased considerably, so biomarkers should be searched to assist in the selection of the optimal treatment agent. The most common of these biomarkers is HLA-Cw6. Objective: The aim was to determine whether there is a relationship between HLA-Cw6-positivity (HLA-Cw6-POS) and the response of treatment agents in psoriasis. Methods: Blood samples of 124 patients were subjected to genetic study for HLA-Cw6. Results: Psoriasis area severity index (PASI) score of more than 75% (PASI75) response was received in 34 (73.9%) of the HLA-Cw6-POS methotrexate-treated patients, 30 (78.9%) of the HLA-Cw6-POS cyclosporine-treated patients, and 8 (37.5%) of the HLA-Cw6-POS acitretin-treated patients. The differences were not statistically significant (P = 0.634-0.071-0.409). PASI75 response was received in 73 (68.2%) of the HLA-Cw6-POS patients in patients treated with conventional agents. In adalimumab-treated patients, PASI75 response was received in 8 (53.3%) of the HLA-Cw6-POS patients, 6 (75%) of the HLA-Cw6-POS infliximab-treated patients, and 4 (57.1%) of the HLA-Cw6-POS ustekinumab-treated patients. The differences were not statistically significant (P = 0.245-1.00-0.322). PASI75 response was received in 24 (64.9%) of the HLA-Cw6-POS and 33 (84.6%) of HLA-Cw6 negative (HLA-Cw6-NEG) patients with biological agents. The biological agent response was statistically significantly lower in HLA-Cw6-POS. Conclusion: None of the agents were affected by HLA-Cw6. When biological agents were evaluated collectively, the treatment response of HLA-Cw6-POS patients was lower.

Vitamin D receptor polymorphisms and bone health after kidney transplantation

Background/aim: Bone disease is one of the most prominent complications after kidney transplantation. Bone diseases include osteoporosis, persistent secondary hyperparathyroidism, and avascular necrosis (AVN). We investigated the relationship between the polymorphisms of the vitamin D receptor (VDR) gene and bone diseases occurring after kidney transplantation. Materials and methods: The study consists of 234 kidney allograft recipients with a minimum follow-up of five years after kidney transplantation. Patients with glomerular filtration rates less than 30 mL/min/1.73m2, a history of parathyroidectomy, bisphosphonate use pre- or post-transplantation, and cinacalcet use posttransplantation excluded. We evaluated associations between the polymorphisms of the VDR gene (BsmI, TaqI, ApaI, FokI, and Cdx2), the first-year bone mineral density (BMD) scores, persistent secondary hyperparathyroidism, and AVN. Results: Patients with low BMD scores were significantly younger (P = 0.03) and had higher intact parathormone (iPTH) levels (P = 0.03). Cdx2 TT genotype significantly increases the risk of low BMD scores (OR: 3.34, P = 0.04). Higher phosphate levels were protective against abnormal BMD scores (OR: 0.53; P = 0.03). Patients with persistent hyperparathyroidism had significantly longer dialysis vintage and higher pretransplantation iPTH levels (P = 0.02 and P < 0.001, respectively). Cdx2, CT/TT, and ApaI CA/AA genotypes significantly increase the risk of persistent hyperparathyroidism (OR: 6.81, P < 0.001, OR: 23.32, P < 0.001, OR:4.01, P = 0.02, and OR: 6.30, P = 0.01; respectively). BsmI CT/TT genotypes were found to increase AVN risk with an HR of 3.48 (P = 0.03). Higher hemoglobin levels were also found to decrease AVN risk with an HR of 0.76 (P = 0.05). Conclusion: Certain VDR gene polymorphisms are associated with a higher risk for bone diseases after kidney transplantation.

Erysipelas-like erythema in children with familial Mediterranean fever.

OBJECTIVES: Erysipelas-like erythema (ELE) is a well-known pathognomonic skin lesion associated with familial Mediterranean fever (FMF). The aim of this study was to describe the clinical and demographic features and phenotypic differences between paediatric FMF patients with and without ELE. METHODS: We retrospectively collected the medical charts of paediatric patients who had been diagnosed with FMF and followed by the Paediatric Rheumatology Department of Gazi University, Turkey, from 2006 to 2016. RESULTS: Among 782 FMF patients, 59 (33 males and 26 females; median age, 11.1±5.1) were found to have ELE. More patients had arthritis in the ELE group than in the other group (p=0.011). Arthritis occurred in the ankle (77.4%), knee (19.3%) and hip (3.2%) joints. The coexistence of arthritis and ELE was seen in 12 (20.3%) patients. All ELE plaques were located on the lower legs and dorsum of the feet. Eleven patients (18.6%) presented with ELE as the initial symptom and were diagnosed with FMF, and 48 (81.4%) patients experienced ELE attacks while receiving colchicine therapy. The median dose of colchicine at last visit, PRAS activity score and M694V homozygous mutation status were significantly higher in the ELE group than in the other group (p=0.041, p=0.001 and p=0.023, respectively). CONCLUSIONS: ELE is an uncommon but important feature of FMF. In patients with ELE, arthritis is more frequently encountered, and M694V homozygous mutation is more frequently found. FMF patients with ELE have more severe disease activity, and they use higher doses of colchicine in relation to this severe disease course.

Sacroiliitis associated with familial Mediterranean fever in childhood: a case series and review of literature.

BACKGROUND AND OBJECTIVES: Familial Mediterranean fever (FMF) is an autosomal-recessive auto-inflammatory disorder characterized by recurrent episodes of fever with serositis. Sacroiliitis associated with FMF is very rare, especially in children. We aimed to describe the demographic, clinical, laboratory features, and treatment responses of pediatric patients with FMF -related sacroiliitis. METHODS: The study consisted of seven pediatric patients younger than 16 years, diagnosed with sacroiliitis associated with FMF between 2010 and 2017. Medical records of patients were retrospectively evaluated. Sacroiliitis was diagnosed based on magnetic resonance imaging. We also reviewed previous studies of FMF related sacroiliitis. RESULTS: Five of the seven patients (male:female ratio of 5:2) had a M694V (homozygous) mutation, one patient had a M694V (heterozygous) mutation, and one patient had a V726A (heterozygous) mutation. All patients were HLA-B27 negative. One of the cases achieved remission with colchicine plus non-steroidal anti-inflammatory drug treatment, and one patient`s symptoms were managed by the addition of sulfasalazine. Four patients responded to etanercept treatment, and one patient`s symptoms were suppressed with canakinumab. CONCLUSION: Sacroiliitis can be seen in pediatric FMF patients suffering with inflammatory back pain. This manifestation generally occurs in FMF patients who have M694V mutation. Etanercept could likely show a beneficial effect in patients who are resistant to disease modifying anti-rheumatic drugs and non-steroidal anti-inflammatory drugs. In addition, canakinumab treatment should be considered as a successful alternative therapy in this rare group of patients.

Ozone application as adjunctive therapy in chronic periodontitis: Clinical, microbiological and biochemical aspects.

BACKGROUND/PURPOSE: The application of ozone as an adjunctive treatment represents a new approach in the management of chronic periodontitis. The purpose of this study was to evaluate the clinical, biochemical and microbiological efficacy of ozone treatment as an adjunct to scaling and root planing (SRP) in generalized chronic periodontitis (GCP) patients. MATERIALS AND METHODS: Eighteen patients (9 males and 9 females; aged from 28 to 47 years, mean age of 40 ± 6.51 years) with GCP were recruited in the study. In a split mouth design, two quadrants in each patient were randomly allocated to SRP-alone or SRP-ozone therapy (SRP + OT) groups by coin toss method. Subgingival plaque and gingival crevicular fluid (GCF) samples were collected at baseline, following 1st and 3rd months. The clinical parameters were monitored at baseline and after 3 months. Microbiological parameters were analyzed by quantitative-PCR and GCF biomarkers were determined by ELISA. Results were analyzed statistically. RESULTS: Statistically significant improvements in all clinical parameters were accompanied by a reduction in microbiological and biochemical parameters in both treatment groups. SRP treatment resulted in a significant reduction of Porphyromonas gingivalis (Pg) at 1st month and Tannerella forsythia (Tf) and Prevotella intermedia (Pi) at 3 months. Following SRP treatment the interleukin (IL)-8 levels were significantly reduced at month 1. There were no significant differences between two treatments for any of the parameters. CONCLUSION: Within the limitations of this study, adjunctive ozone therapy did not provide additional benefits to clinical, microbiological and biochemical parameters over SRP in chronic periodontitis patients.

Serum fetuin-A is associated with the components of MIAC(malnutrition, inflammation, atherosclerosis, calcification) syndrome in different stages of chronic kidney disease

Background/aim: Fetuin-A, a circulating inhibitor of calcification, is a marker of inflammatory-nutritional state. We evaluated the association between serum fetuin-A levels and vascular calcification, intima-media thickness, and nutritional and inflammatory markers in different stages of chronic kidney disease (CKD). Materials and methods: CKD patients were sampled for calcium-phosphate parameters and nutritional and inflammatory markers [highly sensitive C-reactive protein (hs-CRP)], and serum fetuin-A levels. Intima-media thicknesses of the common carotid arteries (CIMT) were measured. Peripheral artery calcification scores were obtained. Results: A total of 238 patients were included in the study. Fetuin-A levels in patients with end-stage renal disease were significantly lower than those in patients with stage-3 and stage-4 CKD (stage-5 vs. stage-4, P < 0.001; stage-5 vs. stage-3, P < 0.001). Fetuin-A was negatively correlated with creatinine (P < 0.001), Ca × P product (P < 0.001), hs-CRP (P = 0.01), vascular calcification score (P < 0.001), and CIMT (P < 0.001), and positively correlated with BMI (P < 0.001, r = 0.30) and serum albumin (P < 0.001). Conclusion: Lower levels of fetuin-A were associated with higher vascular calcification scores, CIMT, hs-CRP levels, and lower BMI and albumin. Fetuin-A deficiency may be a key element for MIAC syndrome.

HLA Genotypes in Turkish Hematopoietic Cell Recipients and Likelihood of Finding a Matched Donor Through Family Searches.

OBJECTIVES: Allogeneic hematopoietic stem cell transplant is a life-saving treatment, but donor numbers in Turkey do not meet the increasing demand for this procedure. Here, our objectives were (1) to assess the frequency of HLA-matched related donors in the Turkish population and (2) to identify the HLA antigens and haplotypes that are most frequent in Turkey. MATERIALS AND METHODS: The HLA genotypes of 841 consecutive recipients and 3071 family members were retrospectively reviewed. RESULTS: Matched related donors were identified for 368/841 recipients (44%). Extended family donor searches were performed for 111/181 pediatric recipients (61%), with nonsibling matched related donors found for 23 patients (21%). Matched related donors were found for a significantly higher proportion of pediatric patients (52%) than adult patients (41%) (odds ratio of 2.5; 95% confidence interval, 1.9-4.1; P = .02). The percentage of pediatric versus adult patients with 3 or more siblings was 13% versus 46% (odds ratio of 5.6; 95% confidence interval, 3.6-8.5; P = .001). The most frequent HLA class I antigens at each locus were HLA-A*02 (20.2%), HLA-B*35 (19.5%), and HLA-C*07 (19.8%). The most frequent HLA class II antigens at each locus were HLA-DRB1*11 (21.6%) and HLA-DQB1*03 (40.2%). The most common 3-locus haplotypes were HLA-A*24 B*35 DRB1*11 (F:0.020) and HLA-A*01 B*08 DRB1*03 (F:0.015). When adult and pediatric groups were combined, the most common locus haplotypes were found in 43/345 sibling donors (12%) and in 7/23 nonsibling pediatric donors (30%) (odds ratio of 2.7; 95% confidence interval, 1.2-6.4; P = .02). CONCLUSIONS: The results indicate that, in Turkey, it can be beneficial to revise donor search algorithms to include an extended family donor search before an unrelated donor search. This type of search can be effective because of the HLA haplotype diversity in Turkey, the frequency of consanguinity, and the country's limited donor pool.

Avaliação de antígeno leucocitário humano classe I e II em pacientes pediátricos com gastrite e úlcera duodenal ativas e Helicobacter pylori positivo / Evaluation of human leukocyte antigen class i and ii antigens in helicobacter pylori-positive pediatric patients with active gastritis and duodenal ulcer

ABSTRACT BACKGROUND: As being the first bacteria determined to be carcinogenic, Helicobacter pylori (H. pylori) is a pathogen localized in the stomach in more than half of the world population. Some earlier studies have found a relation between tissue histocompatibility antigens and gastric cancers depending on the regions. OBJECTIVE: The present study aimed to determine the distribution of human leukocyte antigen (HLA) class I and class II antigens in H. pylori-positive pediatric patients with active gastritis and duodenal ulcer, excluding cancer cases, in our center. METHODS: The study included 40 patients diagnosed with H. pylori-positive active gastritis and duodenal ulcer and 100 controls consisting of healthy donor candidates. The HLA class I and class II antigens were studied in the isolated DNA samples using the polymerase chain reaction sequence-specific oligonucleotide probes. RESULTS: The frequency of HLA-B*51 antigen was significantly higher in the patient group than in the control group (40% vs 17%; P=0.003). There was no difference between the two groups in terms of the frequencies of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. CONCLUSION: It was determined that HLA-B*51 plays a critical role in H. pylori infection.

RESUMO CONTEXTO: Determinada como sendo a primeira bactéria cancerígena, o Helicobacter pylori (H. pylori) é um patógeno localizado no estômago em mais da metade da população mundial. Alguns estudos anteriores têm encontrado uma relação entre câncer gástrico e antígenos de histocompatibilidade de tecido dependendo das regiões. OBJETIVO: O presente estudo teve como objetivo determinar a distribuição em nosso centro do antígeno leucocitário humano (HLA) de classe I e antígenos classe II em pacientes pediátricos H. pylori-positivos com gastrite e úlcera duodenal ativas, excluindo casos de câncer. MÉTODOS: O estudo incluiu 40 pacientes H. pylori-positivos diagnosticados com gastrite e úlcera duodenal ativas e 100 controles consistindo de candidatos doadores saudáveis. Foram estudadas nas amostras de DNA isoladas o antígeno leucocitário humano classe I e antígenos classe II, utilizando-se as cadeias de sequência específica de polimerase do oligonucleotideo. RESULTADOS: A frequência do antígeno HLA - B * 51 foi significativamente maior no grupo de pacientes do que no grupo controle (40% vs 17%; P=0,003). Não houve diferença entre os dois grupos em termos das frequências dos antígenos HLA-A, HLA-DR, HLA-DQ e HLA-C. CONCLUSÃO: Determinou-se que o HLA - B * 51 desempenha um papel crítico na infecção pelo H. pylori.

Investigation of human leukocyte antigen in osteoarticular brucellosis

Background/aim: To determine the relationship between human leukocyte antigen (HLA) antigens and osteoarticular brucellosis by evaluating HLA Class I and II antigens in control subjects and patients developing osteoarticular brucellosis in Turkey.Materials and methods: The study included 28 patients with osteoarticular involvement diagnosed with brucellosis and 100 controls. The HLA Class I and II antigens were studied in isolated DNA samples using sequence-specific oligonucleotide procedure.Results: The mean age of the 28 patients and 100 controls was 42.3 ± 20.2 years and 50.1 ± 16.3 years, respectively. When the frequency of HLA Class I was examined, HLA-A*02 and HLA-B*27 antigens were detected in 50% and 28.57% of the patients, respectively. However, there was no significant difference when compared to the control group. Among the HLA Class I antigens, HLA-Cw*10 was determined in 35.71% of the patients and 17% of the controls; the difference was significant (P = 0.039).Conclusion: In the development of brucellosis, the frequency of HLA-Cw*10 among HLA Class I antigens was observed to be increased, and HLA-Cw*10 was considered likely to cause predisposition to brucellosis. Further studies to be performed on a higher number of patients and controls could demonstrate that genetic factors play a role in the diagnosis of osteoarticular brucellosis.

EVALUATION OF HUMAN LEUKOCYTE ANTIGEN CLASS I AND II ANTIGENS IN HELICOBACTER PYLORI-POSITIVE PEDIATRIC PATIENTS WITH ACTIVE GASTRITIS AND DUODENAL ULCER.

BACKGROUND: As being the first bacteria determined to be carcinogenic, Helicobacter pylori (H. pylori) is a pathogen localized in the stomach in more than half of the world population. Some earlier studies have found a relation between tissue histocompatibility antigens and gastric cancers depending on the regions. OBJECTIVE: The present study aimed to determine the distribution of human leukocyte antigen (HLA) class I and class II antigens in H. pylori-positive pediatric patients with active gastritis and duodenal ulcer, excluding cancer cases, in our center. METHODS: The study included 40 patients diagnosed with H. pylori-positive active gastritis and duodenal ulcer and 100 controls consisting of healthy donor candidates. The HLA class I and class II antigens were studied in the isolated DNA samples using the polymerase chain reaction sequence-specific oligonucleotide probes. RESULTS: The frequency of HLA-B*51 antigen was significantly higher in the patient group than in the control group (40% vs 17%; P=0.003). There was no difference between the two groups in terms of the frequencies of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. CONCLUSION: It was determined that HLA-B*51 plays a critical role in H. pylori infection.

Familial Mediterranean fever gene mutation frequencies in a sample Turkish population.

OBJECTIVES: Our knowledge about the frequencies of mutations in the Turkish population is based on the studies on the affected patients and hospital-based control groups. We aimed to determine the frequencies of MEFV gene mutations in a population-based field study in Turkey. METHODS: Turkish citizens aged between 5 and 65 years were included in the study. Cities from seven regions of Turkey were studied. Blood samples were obtained from individuals who gave permission for laboratory experiments, and they were analysed for 10 MEFV gene mutations. RESULTS: Among 500 participants, MEFV mutations were found in 74 (14.8%). Sixty four (12.8%), 7 (1.4%), and 3 (0.6%) participants were heterozygous, compound heterozygous, and homozygous, respectively. Among inhabitants with heterozygous mutations, the most common heterozygous mutations were E148Q/- and M694V/-. Sixteen participants were found to be heterozygous for M694V, 2 were compound heterozygous for M694V/E148Q, and one was homozygous for M694V/M694V mutation; in total, the frequency of M694V allele was 4% (n=20). Twenty-three (4.6%) individuals were heterozygous for common mutations (M694V, M680I, V726A). Total allelic frequency was 8.4%. CONCLUSIONS: Our study, which describes the MEFV mutational spectrum and distribution in a healthy Turkish population, found a carrier rate that is much higher than expected.

Evaluation of urinary KIM-1, NGAL, and IL-18 levels in determining early renal injury in pediatric cases with hypercalciuria and/or renal calculi.

AIM: One has to measure urinary enzymes and proteins to determine renal dysfunction and tubular injury in earlier stage during the course of disease. The aim of this study was to investigate the role of urinary NGAL (neutrophil gelatinase-associated lipocalin), IL-18 (Interleukin 18), and KIM-1 (kidney injury molecule-1) levels in determining early renal injury in pediatric patients with hypercalciuria (HC) and/or nephrolithiasis (NL) and to compare the levels of these markers between the sick and healthy subjects. MATERIAL AND METHODS: Urinary NGAL, KIM- 1, and IL- 18 levels were measured in 40 pediatric patients diagnosed with NL, 23 patients with HC, and 20 healthy controls. RESULTS: A significant difference was found between patient groups (NL and HC) and healthy children with respect to urinary NGAL/cr ratio (p < 0.001). There were no significant differences between patient and control groups with respect to urinary IL18/cr and KIM1/cr ratios. CONCLUSIONS: We found that urinary NGAL is a useful marker for determining renal tubular damage in NL and HC. To our knowledge, this is the first study to report significantly increased urinary NGAL levels in NL and HC.

Neutrophil gelatinase-associated lipocalin as a follow-up marker in critically ill pediatric patients with established acute kidney injury.

AIM: To assess the utility of neutrophil gelatinase-associated lipocalin (NGAL) in both urine and serum as a follow-up marker for the discrimination of prerenal acute kidney injury (AKI) from intrinsic AKI in critically ill pediatric patients with established AKI at the time of patient presentation. PATIENTS AND METHODS: This was a prospective cohort study of a heterogeneous group of critically ill children in the pediatric intensive care unit (PICU). Serum creatinine (SCr) values were obtained daily as part of routine patient care. AKI was defined as a 50% or greater increase in SCr from baseline and classified as prerenal and intrinsic AKI. RESULTS: A total of 32 critically ill children (mean age: 105 ± 71.7 months, 56% female) with established AKI were included to the study. Area under curve (AUC) for urine and serum NGAL to distinguish prerenal AKI from intrinsic AKI was 0.94, 95% confidence interval (CI): 0.869-1.02 (p < 0.001) and 0.86, 95% CI: 0.71-1.02 (p = 0.002), respectively. CONCLUSION: In a heterogeneous group of critically ill children with established AKI, we found that NGAL in both urine and serum at the time of patient presentation discriminated intrinsic AKI from prerenal AKI.

The association of cytokine gene polymorphism with reflux nephropathy.

OBJECTIVE: To identify genetic risk factors for the progression of vesicoureteral reflux (VUR) to reflux nephropathy, we examined polymorphisms of multiple cytokine genes among VUR patients with or without renal scarring. METHODS: A total of 238 VUR patients aged between 1 and 18 years with (n = 113) or without renal scarring (n = 125) were included. The presence of renal scarring was demonstrated by renal parenchymal examination using Technetium-99m dimercaptosuccinate scintigraphy. Sera of the patients were examined for tumor necrosis factor-alpha (TNF-α, -308), transforming growth factor-beta1 (TGF-ß1, +869, +915), interleukin-6 (IL-6, -174), interleukin-10 (IL-10, -1082, -819, -592) and interferon-gamma (IFN-γ, +874) gene polymorphisms using the polymerase chain reaction sequence-specific primer method. RESULTS: Among patients with renal scarring, frequencies for the T/T G/C and C/C G/C genotypes of TGF-ß1 gene (p = 0.003), GCC/GCC genotype of IL-10 gene (p = 0.015), GC phenotype of IL-6 gene (p = 0.001) and T/T genotype of IFN-γ gene (p = 0.001) were higher compared to patients without renal scarring. Regarding the TNF-α gene, among patients with low grade VUR only, the G/G genotype was associated with an increased risk. CONCLUSIONS: Certain genotypes of cytokine gene polymorphisms seem to be associated with an increased or decreased susceptibility to reflux nephropathy, which may explain why only a proportion of VUR patients progress to reflux nephropathy. This information may aid in prediction of prognosis and implementing more aggressive management strategies at earlier stages. Further immunogenetic studies may identify novel targets for the management and prevention of the condition.