Significant associations of the rs3104413 single-nucleotide polymorphism in the hla region with type 1 diabetes

Background and Aims: In this study, the effect of rs310441 polymorphism in the human leukocyte antigen [HLA] region on the development of susceptibility or resistance to Type 1 diabetes [T1D] among the people with T1D compared to healthy subjects has been investigated

Materials and Methods: This research, which is based on the examination of 130 cases with T1D and 98 controls, has been carried out in the city of Hamedan after clinical examination. In order to determine the HLA gene polymorphism, the allele-specific-refractory mutation system-polymerase chain reaction [ARMS-PCR] method was utilized

Results: This study indicated that there is a significant relationship between the frequency of alleles and genotypes in the patients compared to healthy subjects. The C/C and C/G genotypes were more frequent in patients than controls and G/G genotype was shown to be protective for T1D [p=0.01]. Significant difference was found for the G allelic frequency in patients with T1D and in the control group. The allelic frequency was significantly different between the two groups [p=0.0001]. Our findings indicate that HLA polymorphism[C/G] and [C/C] genotypes could be considered as genetic risk factors associated with susceptibility and [G/G] genotypes associated with protection for T1D

Conclusions: This study identified that there is a significant relationship between the frequency of alleles and genotypes in the patients compared to healthy subjects

Ameliorative Effects of Nilotinib on CCl4 Induced Liver Fibrosis Via Attenuation of RAGE/HMGB1 Gene Expression and Oxidative Stress in Rat / 전남의대학술지

Nilotinib as a tyrosine kinase inhibitor has been recently used to improve the liver fibrosis process, but the exact mechanisms still require further clarification. In this study, we investigated the anti-fibrotic effects of Nilotinib via RAGE/HMGB1axis and antioxidant mechanisms. This experimental study was performed in the Hamadan University of Medical Sciences, Iran, from May 2015 to December 2016. Liver fibrosis was induced in Wistar male rats by CCL₄. Rats were gavaged daily with Nilotinib (10 mg/kg). RAGE, HMGB1, TNF-α and TGF-β mRNA expression were evaluated by quantitative RT-PCR. TNF-α protein levels were measured using the immunoassay method. Thiol groups, carbonyl groups, nitric oxide levels and glutathione peroxidase activity were measured by spectrophotometric methods.The results showed that Nilotinib decreased TNF-α, TGF-β, RAGE and HMGB1 mRNA expression (p<0.001) in the liver tissues of the fibrosis group. Nilotinib also decreased carbonyl groups and nitric oxide levels and increased thiol groups and glutathione peroxidase activity in the fibrosis groups. The histopathological changes were found to be attenuated by Nilotinib. In conclusion, Nilotinib can improve liver fibrosis and open new mechanisms of the anti-fibrotic properties of Nilotinib.

Ameliorative Effects of Nilotinib on CCl4 Induced Liver Fibrosis Via Attenuation of RAGE/HMGB1 Gene Expression and Oxidative Stress in Rat / 전남의대학술지

Nilotinib as a tyrosine kinase inhibitor has been recently used to improve the liver fibrosis process, but the exact mechanisms still require further clarification. In this study, we investigated the anti-fibrotic effects of Nilotinib via RAGE/HMGB1axis and antioxidant mechanisms. This experimental study was performed in the Hamadan University of Medical Sciences, Iran, from May 2015 to December 2016. Liver fibrosis was induced in Wistar male rats by CCL₄. Rats were gavaged daily with Nilotinib (10 mg/kg). RAGE, HMGB1, TNF-α and TGF-β mRNA expression were evaluated by quantitative RT-PCR. TNF-α protein levels were measured using the immunoassay method. Thiol groups, carbonyl groups, nitric oxide levels and glutathione peroxidase activity were measured by spectrophotometric methods.The results showed that Nilotinib decreased TNF-α, TGF-β, RAGE and HMGB1 mRNA expression (p<0.001) in the liver tissues of the fibrosis group. Nilotinib also decreased carbonyl groups and nitric oxide levels and increased thiol groups and glutathione peroxidase activity in the fibrosis groups. The histopathological changes were found to be attenuated by Nilotinib. In conclusion, Nilotinib can improve liver fibrosis and open new mechanisms of the anti-fibrotic properties of Nilotinib.

Evaluation of interleukin 8 +2767 A/T polymorphism in visceral leishmaniasis

OBJECTIVE@#To evaluated the relationship between the genetic variations at IL-8 +2767 position with VL pathogenesis among Iranian patients.@*METHODS@#Three groups including patients with VL clinical presentation and leishmania seropositive (n = 124), patients seropositive but without clinical presentation (n = 82) and healthy controls (n = 63) were selected to conduct this cross-sectional study. Polymorphism at +2767 position of IL-8 was investigated using PCR-RFLP techniques. Anti-leishmania antibody titration was evaluated by the immunoflorescence technique.@*RESULTS@#We observed higher significant frequencies +2767 A/A and A/T genotypes in Group 1 compared to Group 2 and healthy controls (P = 0.001). Also, patients in Group 1 carrying A/A genotype showed higher titer of anti-leishmania antibody than patients with A/T and T/T genotypes (P = 0.05). The validity of the data was analyzed using Hardy-Weinberg equilibrium and one way analysis of variance (ANOVA), as well as χ tests.@*CONCLUSIONS@#Our findings indicate that the IL-8 +2767 polymorphism is significantly involved in impaired immune responses against VL and it could be considered as a risk factor for the VL progress.

Evaluation of interleukin 8 +2767 A/T polymorphism in visceral leishmaniasis

Objective To evaluated the relationship between the genetic variations at IL-8 +2767 position with VL pathogenesis among Iranian patients. Methods Three groups including patients with VL clinical presentation and leishmania seropositive (n = 124), patients seropositive but without clinical presentation (n = 82) and healthy controls (n = 63) were selected to conduct this cross-sectional study. Polymorphism at +2767 position of IL-8 was investigated using PCR-RFLP techniques. Anti-leishmania antibody titration was evaluated by the immunoflorescence technique. Results We observed higher significant frequencies +2767 A/A and A/T genotypes in Group 1 compared to Group 2 and healthy controls (P = 0.001). Also, patients in Group 1 carrying A/A genotype showed higher titer of anti-leishmania antibody than patients with A/T and T/T genotypes (P = 0.05). The validity of the data was analyzed using Hardy–Weinberg equilibrium and one way analysis of variance (ANOVA), as well as χ

HLA-KIR interactions and immunity to viral infections

Host genetic factors play a central role in determining the clinical phenotype of human diseases. Association between two polymorphic loci in human genome, human leukocyte antigen [HLA] and killer cell immunoglobulin-like receptors [KIRs], and genetically complex infectious disease, particularly those of viral etiology, have been historically elusive. Hence, defining the influence of genetic diversity in HLA and KIRs on the outcome of viral infections has been extensively started in clinically well-defined cohort studies. HLA genes encode molecules which present antigenic peptide fragments to T lymphocytes as central players in adaptive immunity against infectious diseases. KIRs are expressed on natural killer cells which perform a crucial role in innate immunity to pathogen infection. The effector functions of NK cells such as direct killing of infected cells, cytokine production, and cross-talk with adaptive immune system depend on activation of NK cells, which is determined by their surface receptors. Among these receptors, KIRs, which interact with HLA class I, are mainly inhibitory and exhibit substantial genetic diversity. An extensive body of association studies indicates a role for HLA-KIRs interactions in infectious diseases, autoimmune disorders, cancer, transplantation, and reproduction. Various compound HLA-KIR genotypes appear to affect outcome of viral infections that suggests a role for HLA class I diversity in innate immunity as well as adaptive immune responses. The aim of this review is focusing on the impact of HLA and KIR alleles and different combinations of these alleles on clinical outcome of viral diseases to validate this proof-of-concept with respect to the therapeutic interventions

L-selectin Phe206Leu gene polymorphism is not associated with visceral leishmaniasis

Previous studies revealed that selectins play key roles in homing of immune cells to inflamed tissues and lymphatic organs. L-selectins are expressed on immune cells and interact with P and E selectins to homing to the tissues, hence, the polymorphisms within the gene of L-selectins may are associated with alteration in its expression. Thus, the current cross-sectional analytical study has been designed to investigate the polymorphisms within L-selectin gene and their relation with visceral leishmaniasis [VL]. This study was performed on 194 samples during 2004-2012.The PCR-SSP and immunoflorescence techniques were used to evaluate the L-selectins polymorphism and anti-Leishmaniaantibody titration, respectively, in 56, 74 and 64 seropositive VL patients [group 1], seropositive healthy controls [group 2] and seronegative healthy controls [group 3]. The results showed that the genotypes [P=0.711] and alleles [P=0.679] within L-selectins gene [A/C] was not differ between groups. Our results also demonstrated that the genotypes within L-selectins in group 1 [P=0.807] and 2 [P=0.441] were not associated with the titration of anti-leishmania antibody. The results identified that the polymorphisms within L-selectins gene were not associated with VL and it may be concluded that these genotypes and alleles are unable to affect immune responses in VL patients

Concomitant increase of OX40 and FOXP3 transcripts in peripheral blood of patients with breast cancer

Regulatory T cells [T-regs] have an important role in cancer by suppression of protective antitumor immune responses. Regulatory T cells express the forkhead/ winged helix transcription factor [FOXP3] and OX40 molecules which have important regulatory roles in the immune system. To evaluate FOXP3 and OX40 transcripts in the peripheral blood mononuclear cells of women with breast cancer. Blood samples from 40 women with histologically-confirmed infiltrating ductal carcinoma of the breast and 40 healthy volunteer women without a history of malignancy or autoimmune disorders were collected. The abundance of FOXP3 and OX40 gene transcripts were determined by quantitative real-time PCR [qRT-PCR]. There was a significant positive correlation between FOXP3 and OX40 gene expression in women with breast cancer in a stage dependent manner. This finding emphasizes the importance of T-regs as predominant targets for breast cancer immunotherapy

Anti-HLA antibodies and kidney allograft outcomes in recipients with donor bone marrow cell infusion

Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concurrent donor bone marrow cell infusion [DBMI]. Between June 2006 and May 2007, forty living unrelated donor kidney transplants consisting of 20 recipients with DBMI and 20 without infusion entered into the study and were monitored prospectively for one year. Pre-and post-transplant [days 14, 30, and 90] sera were screened for the presence of anti-HLA class-I and II antibodies, and subsequently positive sera retested with ELISA specific panel for antibody specification. Of 40 patients, 9 [22.5%] experienced acute rejection episodes [ARE] [6/20 cases in non-infused versus 3/20 in DBMI patients]. The prevalence of anti-HLA antibodies before and after transplantation were higher in patients with ARE compared to non-rejecting ones [88.8% vs. 38.7%, p=0.01 and 66.6% vs. 25.8%, p=0.04, respectively]. A total of 10% [4/40] of patients developed donor specific anti-HLA antibodies [DSA] and in this regard 2 patients from the control group experienced ARE. All 3 rejecting patients in DBMI group were negative for DSA and positive for non-DSA. The lower titer of post-transplant anti-HLA antibodies were shown in DBMI patients compared to pre-transplantation titer. Additionally, the average serum creatinine levels during one year follow up and even in those patients with ARE were lower compared to controls. Our findings reveal an association between pre-and post-transplant anti-HLA antibodies, and ARE and also early allograft dysfunction. It suggests that lower incidence of ARE, undetectable DSA, lower titer of antibodies concomitant with a decrease in serum creatinine level, better allograft function and lower percentages of PRA in DBMI patients, could be the probable manifestations of partial hypo-responsiveness against allografts

High frequency of clinically significant infections and cytomegalovirus disease in kidney transplant recipients with serum mannose-binding lectin deficiency

Mannose-binding lectin [MBL] constitutes defense against infections when adaptive immune response is compromised. Elevation in serum MBL levels has been shown in patients with kidney failure. We compared serum MBL levels before and after kidney transplant and evaluated association of MBL deficiency with infectious complications in kidney transplant recipients. This study was performed in 71 kidney transplant recipients and 48 healthy controls. In 36 recipients [group 1], serum MBL levels were tested before and on days 7 and 14 after transplantation. They were followed up for 6 months. In 35 recipients [group 2], serum MBL was measured during their posttransplant follow-up visits. In both groups, frequencies of clinically significant infections and acute rejection were compared between those with low MBL [< 500 ng/mL] and normal/high MBL [< 500 ng/mL]. Serum MBL levels [1744 +/- 905 ng/mL] were not higher in group 1 before transplantation than in controls. One and 2 weeks after transplantation, MBL levels decreased to 1699 +/- 1030 ng/mL and 1562 +/- 1020 ng/mL, respectively. Five patients who had low serum MBL levels experienced more frequent episodes of infections [P = .008] and CMV disease [P < .001]. Ten patients in group 2 with low MBL levels had more frequent episodes of CMV disease [P = .01]. These findings suggest a potential role for MBL in defense against developing posttransplant CMV disease and that low serum MBL levels in kidney transplant recipients be considered an indicator of the need for CMV prophylaxis

HLA class II allele and haplotype frequencies in Iranian patients with leukemia

Previous studies demonstrated significant differences in a number of HLA allele frequencies in leukemia patients and normal subjects. In this study, we have analyzed HLA class II alleles and haplotypes in 110 leukemia patients [60 acute myelogenous leukemia "AML", 50 chronic myelogenous leukemia"CML"] and 180 unrelated normal subjects. Blood samples were collected from all of the patients and control subjects. DNA was extracted by salting out method and HLA typing was performed using PCR-SSP method. Significant positive association with AML was obtained for HLA-DRB1*11allele [35% vs. 24.7%, P=0.033]. Two alleles including HLA-DRB4 and-DQB1*0303 were significantly less frequent in AML patients than in controls. HLA-DQB1*0303 allele was never observed in CML patients compared with allele frequency in controls [4.2%]. According to haplotype analysis, HLA-DRB1*0101/DQA1*0104/-DQB1*0501 frequencies were significantly higher and-DRB1*16/-DQA1*01021/-DQB1*0501 frequencies were significantly lower in CML patients than in controls .In conclusion it is suggested that HLA-DRB1*16 allele and HLA-DRB1*15/-DQA1*0103/-DQB1*06011 and-DRB1*16/-DQA1*01021/-DQB1*0501 haplotypes predispose individuals to AML and HLA-DRB4 allele predispose to CML. Future studies are needed to confirm these results and establish the role of these associations in AML and CML