Tehran University Medical Journal

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Background and Aim: The better understanding of immunopathologic mechanism of tuberculosis (TB) is necessary for the production of new vaccines and adjunctive immunomodulator drugs. Intended to this object, the following study including the measurement of serum concentrations of Th1 (Interferon (IFN)-y and interkeukin (IL)-2 and Th2 cytokines(IL-4AND IL-10 ) in patients with sputum smear-positive pulmonary TB and comparisons of them with PPpositive healthy persons, was designed.

Materials and Methods: The HIV-negative patients that had sputum smear-positive pulmonary TB as defined WHO criteria and hospitalized in the infectious diseases ward of Imam Khomeini hospital or referred to health care centers in the south of Tehran, were included in the study. The PPD-positive healthy persons who were close contacts with pulmonary TB patients, were considered as control group.

Results: In this research 34 active pulmonary TB patients (including17men and 17 woman)and 23 healthy persons with PPD skin test results  or = 10mm (including 12men and 11 woman) were studied. The mean ages of the patients and the healthy persons were 73 and 41 years and 74 and 27 years, respectively. The mean serum IFN-Y concentration was significantly higher in TB patients but the mean serum IL-2 IL-4and IL-10 concentrations were significantly higher in healthy persons. The com parison of the mean serum levels of these cytokines before and during treatment (about 2 months after starting treatment) showed that the amounts of IFN-y and IL4 were increased and the amounts of IL2 and IL-10 were decreased but only the changes of IL-10 were statistically significant. There were no effect on the cytokine changes before and during treatment by age and gender of the patients.

Conclusion: The results of the study of serum Th1 and Th2 cytokines in pulmonary TB patients were different in comparison with the results of the studies of peripheral blood mononuclear cells (PBMCs) stimulated with M.tuberculosis antigens. SO, the simultaneous measurement of them in serum, pleural fluid, BAL fluid and the medium culture of PBMCs stimulated with the antigens is recommended.

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Background: The outcome of acute hepatitis B infection may be influenced by host genetic factors like human leukocyte antigen (HLA). To investigate the association between the HLA-DRB, DQA1 and DQB1 alleles and chronic hepatitis B infection, 50 patients with chronic hepatitis B (based on 6 months positive of HBsAg and HBc antibody and HBeAg and antibody by serological test), were selected from Turkman population in north east of Iran .Allele frequency in patients were compared with a 65 aged and sex match control group from healthy blood donor of that ethnic population.
Methods: HLA DRB, DQA1 and DQB1 alleles were determined using polymerase chain reaction based on sequence specific primer (PCR-SSP) method. Allele frequencies in patients and control subjects were compared by Epi-info statistical soft-wear.
Results: There was a significant increase and positive association in HLA-DRB1*0301, DQA1*0501 and DQB1*0604 allele frequency in patients group while the frequency of HLA-DRB1*1301, 1501 and DQB1*0401 and DQA1*0401, 0102 were lower in patients than control group and shows negative association.
Conclusion: In Iranian Torkman population, HLA DRB1*0301, DQA1*0501 and DQB1*0604 have an important role in susceptibility to chronic hepatitis B infection and HLA DRB1*1301, 1501, DQB1*0401 are associated with protection to chronic hepatitis B infection. Larger case control studies may be helpful to confirm our investigation.

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Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with presumed autoimmune origin. T cells are considered to play a pivotal role in orchestrating the self-reactive immune responses in multiple sclerosis (MS). This study was performed to investigate the role of polymorphisms of the programmed cell death 1 (PD-1) gene on susceptibility to ankylosing spondylitis.This gene codes an immunoreceptor named PD-1, which has a cytoplasmic domain containing two tyrosine residues located within immunoreceptor tyrosine-based inhibitory and switch motifs (ITIM and ITSM), suggesting that PD-1 is predominantly inhibitory which responsible for the negative regulation in T cell activation and peripheral tolerance. We investigated whether PD-1 gene polymorphism is a genetic modifier for risk and progression of MS.Methods: Blood samples from 150 Iranian Relapsing-Remitting MS patients (mean age, 34.98 years) and 202 healthy controls (mean age, 30 years) were enrolled in this study.The PD-1.3 (7146 G/A Intron 4) and PD-1.9 (7625 C/T Exon 5) polymorphisms were detected by Polymerase Chain Reaction and Restriction Enzyme digestion or Restriction Fragment Length Polymorphism (PCR-RFLP). Results: No significant association of the mutated alleles with the disease were detected. Because of the ethnic group genetic variation, our data is not like some of Asian population such as Korea and China.Conclusions: Our data suggest that PD-1 polymorphisms are not act as genetic modifiers of the progression of MS, possibly these polymorphisms don't induce a partial defect in PD-1 mediated inhibition of T-cell activation.

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Background: Based on the reports, high frequency of special alleles of HLA class II genes might be associated with susceptibility to or protective from a particular cancer. These alleles might vary depending on the geographical region. Here we investigate the association between alleles of HLA class II genes and breast cancer in Iranian women.
Methods: 100 patients with pathologically proved breast cancer who referred to Cancer Institute, Tehran University of Medical Sciences in Tehran, Iran, were divided to two groups based on ages (40 years old and less/ or more than 40 years old) and were randomly selected and compared with a group of 80 healthy blood donor subjects. HLA class II alleles were determined by amplification of DNA with polymerase chain reaction (PCR) method followed by HLA-typing using sequence-specific primer (SSP) for each allele.
Results: The most frequent alleles in the DR and DQ regions in group 1 (40 years old and less) in comparison with control group were HLA-DQA1*0301 (p=0.002) and HLA-DQB1*0302 (p>0.05). In contrast HLA-DQA1*0505 (p=0.004) had significantly lower frequency in this group compared with control group. Patients of group two (more than 40 years old) had a higher frequencies of HLA-DQA1*0301 (p=0.001) and HLA-DRB1*1303 (p=0.02) and a lower frequency of HLA-DQA1*0101 (p=0.002) compared to healthy control.
Conclusion: These findings provide information of a positive and negative association between certain alleles of HLA class II and breast cancer in our population and also might support that the pattern of inheritance in the early and late onset of breast cancer differ substantially.

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Background: HLA disease association was investigated in several autoimmune, cancer and infectious diseases. The outcome of tuberculosis (TB) infection may be influenced by host genetic factors like MMP-1, MCP-1, IL-10, IL-12, TNF-α, IFN-γ and human leukocyte antigen (HLA). Given the paucity of information with regard to the association between the human leukocyte antigens (HLA) and TB infection among Iranians, we aimed to identify HLA polymorphisms that might confer susceptibility or protect against TB.

Methods: In this case-control study, to investigate the association between the HLA-DRB1 and DQB1 alleles and TB, 50 patients with tuberculosis were selected from Sistani population in Golstan University of Medical Sciences, Golestan Province, North East of Iran, from September 2015 to February 2016. Allele frequencies in patients were compared with a 100 aged and sex match control group from healthy blood donor of that ethnic population. HLA-DRB1 and -DQB1 alleles were determined using polymerase chain reaction based on sequence specific primer (PCR-SSP) method by low to intermediate resolution kits supplied by CTS (Collaborative Transplant Study, Heidelber University, Germany). Using EPI-info statistical software Chi-square test and fisher exact test, 95% confidence interval and odd ratio were calculated and allele frequencies in patients and control subjects were compared. P-value less than 0.05 were considering statistically significant.

Results: The results of this study showed a significant increase and positive association  with -DRB1*04:03 (OR=3.13, CI 95% (2.47-3.96), -DRB1*14:04 (OR=3.13, CI 95% (2.47-3.96), -DQB1*0201 (OR=2.67, CI 95% (1.18-6.04), -DQB1*0601 (OR=3.16, CI 95% (1.36-7.73) ,while the frequency of -DRB1*07 (OR=0.16, CI 95% (0.05-0.52) were lower in patients than control group and shows negative association.

Conclusion: The results of this study confirmed some of the previous positive and/or negative association, however it is suggested that HLA-DRB1*04:03, -DRB1*14:04, -DQB1*0201, -DQB1*0601- have an important role in susceptibility to tuberculosis infection and -DRB1*07 was associated with protection in Iranian Sistani population. Larger case-control sample size studies may be helpful to confirm our investigation. In addition population-specific studies is needed for evaluation of the role of HLA polymorphisms in tuberculosis in different ethnic groups.