Cytokine profile, Treg/Th17 cell frequency changes during different posttransplantational time points in patients undergoing renal transplantation.

Renal transplantation is the best therapeutic approach for end stage renal dysfunction patients. There are direct relationships between proportions of Treg cells, Treg/Th17 cells ratio and secreted immunosuppressive cytokines with increased survival rate of the transplanted organ. The aim of this study was the measurement of Treg and Th17 cells frequency and their secreted cytokines. Ninety renal-transplanted patients were divided in three groups based on times after transplantation (1-6 month, 6-36 month, and more than 3 years). Treg and Th17 cells frequency, expression level of their transcription factors and cytokines, and their secreted cytokines level were measured in these groups. Higher expression level of Interleukin (IL)-10 and FoxP3 mRNA were observed in patients who had longer posttransplantation time. In contrast, lower mRNA expressions of IL-6, IL-17, IL-23, and TGF-ß were observed in this group. Receptor γt showed no significant changes in studied groups. In addition IL-10 level was increased and IL-6, IL-17, IL-23, and TGF-ß level were decreased in patients who had longer posttransplantation time. Treg cells frequency was raised in mentioned group whereas no remarkable changes were observed in Th17 cell frequency. The present study declared that in stable renal transplantation, over time, the percentage of Treg cells and Treg/Th17 ration is increased. This increase in ratio induces a change in cytokine profile, resulting in an increased immunosuppressive cytokines such as IL-10 leading to increase in the survival rate of the transplanted organ.

Investigation of follicular helper T cells, as a novel player, in preeclampsia.

Preeclampsia (PE) is characterized by hypertension and proteinuria. It occurs in an around 3% to 5% of all pregnancies worldwide. The fetus is kind of semiallograft to the maternal host; immune system components encounter fetal antigens and develop adverse immune responses. Recently, it has been observed that the immune system plays an important role in PE. In the current study, we have tried to investigate the role of follicular helper T (Tfh) cells in the pathogenesis of PE. Blood samples of 49 PE women and 50 healthy controls were collected. Peripheral blood mononuclear cells were isolated, cells were cultured, and then RNA was extracted. Autoantibody and secretory cytokine levels were analyzed by ELISA. Tfh frequency and transcription levels of the related molecules and cytokine were assessed by flow cytometry and real-time PCR, respectively. The frequency of circulating Tfh cell in PE women was significantly higher compared with the healthy pregnant woman (Tfh cells with CD4+ ICOS + , P = 0.0064 and Tfh cells with CD4 + CXCR5 + , P = 0.029). Moreover, mRNA expression levels of CXCR5, BCL6, IL-21, and IL-6 ( P = 0.0006, P = 0.008, P = 0.0063, and P = 0.027, respectively) were upregulated in PE patients. Furthermore, IL-6 ( P = 0.0014) and IL-21 ( P = 0.0059) levels in both group were assayed and the results showed increased in patient group. We also measured autoantibody levels including antiphospholipid antibodies ( P = 0.0001), anticardiolipin antibodies ( P = 0.0004), anti-TPO ( P = 0.0008), anti-TG ( P = 0.001) in circulation of PE group, which were higher than the control group. This study provided insights into the involvement of Tfh cells in etiology and pathogenesis of PE, probably by developing autoantibodies.

Age-Related Prostate Specific Antigen Reference Ranges in Healthy Northern Iranian Men.

BACKGROUND: Prostate cancer is the third most common malignancy in men worldwide. Despite being a helpful biomarker in prostate cancer, prostate specific antigen (PSA) is affected by different factors including age, lifestyle, geographical region and ethnicity. OBJECTIVE: To determine the age specific serum PSA level among healthy Northern Iranian men and to compare the results of our study with the findings of other populations in the world. METHODS: A total of 1271 men who were referred for routine check-up in a multispecialty hospital in the city of Rasht, in Northern Iran, were evaluated for their PSA levels by commercial ELISA method. RESULTS: The normal age related prostate specific antigen range (0-95th percentile) in our study was 0.0-0.62 in men younger than 40 yrs; 0.0-0.75 ng/ml in 40-49 yrs; 0.0-0.91 ng/ml in 50-59 yrs; 0.0-1.33 ng/ml in 60-69 yrs; 0.0-1.45 ng/ml in 70-79 yrs group and 0.0-1.93 in subjects older than 80 yrs. CONCLUSION: The present study revealed the lowest upper limit of PSA level in all age groups in comparison to populations from different countries.

Effect of thermal stress on MICA/B induction in a human liposarcoma cell line.

BACKGROUND: A possible mechanism by which hyperthermia enhances tumor immunogenicity is the induction of NKG2D ligands on tumor cells. Although the expression of MHC class I chain-related protein A and B (MICA/B) has previously been reported in different carcinomas, there is no information about MICA/B expression in liposarcomas. OBJECTIVE: To investigate MICA/B induction in a human liposarcoma cell line (SW-872) after thermotherapy. METHODS: SW-872 and HeLa cell lines were subjected to thermal stress for 1 h at 42, 44 and 46C, and after 2, 4 and 6 h of incubation at 37C, MICA/B expression was assessed at the mRNA and protein levels. RESULTS: Despite high levels of MICA/B transcripts in SW-872 cells at baseline, the expression of these genes decreased significantly at both the mRNA and protein levels after almost all thermal treatments. CONCLUSION: Our data conclude that thermotherapy under 42-46 C had no effect on MICA/B induction on SW-872 liposarcoma cell line but the effects of fever-range temperatures remain to be tested on this cell line.

Association of left ventricular hypertrophy with high-sensitive C-reactive protein in hemodialysis patients.

BACKGROUND: Micro inflammation and cardiovascular disease such as left ventricular hypertrophy (LVH) are common in hemodialysis (HD) patients. Hence, we have evaluated the relationship between high-sensitive C-reactive protein (hs-CRP), as an inflammation marker, and left ventricular mass index (LVMi) and left ventricular mass (LVM) in HD patients. METHODS: An analytical cross-sectional study was performed in 104 HD patients. Serum hs-CRP, LVMi, LVM, and blood pressure were evaluated; demographic data and duration of HD were also recorded. Finally, results were analyzed by using Student's t test, Pearson's correlation coefficient, one-way ANOVA and multiple regression to determine the relationship between LVMi and other variables. RESULTS: A total of 66 male patients (63.46 %) and 38 female patients, with a mean age of 51.75 ± 15.98 years-old, participated in this study. Hypertension was the most common underlying disease (65.4 %). The mean LVMi was 366.98 ± 120.89 g/m(2) and the mean hs-CRP was 8.55 mg/l. Eighty-nine percent of patients had LVH. The hs-CRP level was significantly associated with age and with LVM (P = 0.0001, P = 0.039, respectively). On multivariate analysis, hs-CRP and systolic blood pressure were found to be independent predictors of LVM and LVMi. CONCLUSIONS: This study shows that hs-CRP and systolic BP are independent predictors of LVH in HD patients.

Programmed death-1 gene polymorphism (PD-1.5 C/T) is associated with colon cancer.

Programmed death-1 (PD-1), expressed by activated T cells, is a negative regulator of T lymphocytes. The associations of the immune response-related genes with cancer have been demonstrated. In this study, the PD-1.5 C/T (+7785) polymorphism was investigated in 200 colorectal cancer patients and 200 healthy individuals as controls by nested polymerase chain reaction-restriction fragment length polymorphism method. The genotype and allele frequencies at PD-1.5 position were not significantly different between control individuals and the overall colorectal cancer patients. However, subdivision of the patients by the location (175 colon cancer and 25 rectal cancer) revealed a significant difference between colon cancer patients and healthy individuals (p=0.026), and between colon and rectal cancer patients (p=0.017). The frequency of the CT genotype was significantly higher in colon cancer patients than in control individuals (58.3% vs. 44.8%, Bonferroni corrected p-value=0.024; OR=1.74; 95% CI=1.15-2.62), and in rectal cancer patients (58.3% vs. 28.0%, Bonferroni corrected p-value=0.012; OR=3.59; 95% CI=1.42-9.04). Characteristics of the patients including age, sex, tumor grade and stage were not associated with the PD-1.5 polymorphism. Our results show a significant association between PD-1.5 polymorphism and colon cancer. Larger numbers of patients are required to investigate comprehensively the association of rectal cancer with PD-1.5 polymorphism.

ctla-4 gene variations may influence cervical cancer susceptibility.

BACKGROUND: CTLA-4 is the key player of the immune tolerance. Particular genotypes of ctla-4 have been reported to be associated with various diseases. OBJECTIVE: We aimed to evaluate the role of four single nucleotide polymorphisms (SNPs) of ctla-4 gene in cervical cancer. METHODS: 55 patients and 110 healthy controls were genotyped for four polymorphic loci, three in promoter region; -1722(T/C), -1661(A/G), -318(C/T) and one in exon 1; +49(A/G) using PCR-ARMS and -RFLP methods. RESULTS: At position -1661 the frequency of A/A homozygote and A allele were lower in patients than in controls. (P=0.01, P=0.035; respectively), while at position -318 the frequency of C/C homozygote and C allele were increased in patients (P=0.021, P=0.025; respectively). These significances, however, do not stand the Bonferroni correction suggesting that the effect of multiple comparisons should not be ignored. The haplotype analysis demonstrated 9 haplotypes, of which, 5 were observed in both groups with no significant different frequencies. The TGTA haplotype, however, was only observed in control group (9.54%, p=0.002) and the TGCG haplotype was only occurred in cervical cancer patients (6.48%, p=0.0003). The differences were still significant after Bonferroni correction. CONCLUSION: As a conclusion TGTA haplotype as well as A allele at position -1661 might imply a protective role whereas TGCG haplotype as well as C allele at locus -318 might render susceptibility to cervical cancer. Investigation of ctla-4 gene variants in other ethnic populations will consolidate the findings of this study.