Iranian Journal of Immunology

Molecular prognostic and predictive factors have extensively been studied in different cancers during the past decades, some of which were found to be useful in diagnosis, follow up or even treatment of some malignant tumors. To assess the significance of c-erbB-1, c-erbB-2 and p53 expression in head and neck tumors among Iranian patients and their correlation with known prognostic factors, samples from 53 patients with squamous cell carcinomas of larynx and tongue were studied immunohistochemically. Strong immunoreactivity of c-erbB-1, c-erbB-2 and p53 was observed in 37 (70%), 40 (76%) and 37 (70%) of cases, respectively. The coexpression of these molecules was detected in 27 (50.9%) samples. Neither histological grading nor nodal involvement revealed correlation with c-erbB-1 and/or c-erbB-2 expression. No correlation was found between p53 expression and histological grade. However, a significant positive association was observed between p53 expression and nodal involvement. This data, which is the first report on head and neck squamous cell carcinomas (HNSCC) in Iran, indicates the significance of p53 protein expression which may result from p53 tumor suppressor gene inactivation in lymph node metastasis of HNSCC among Iranian patients. q

To evaluate and compare the usefulness of IS6110-restriction fragment length polymorphism (RFLP) and spoligotyping in the epidemiology of tuberculosis in Iran, Mycobacterium tuberculosis complex strains, isolated in 2 different areas of Iran, were subjected to RFLP and spoligotyping. The average number of IS6110 copies per strain was 11 and ranged from 5 to 18 among the M. tuberculosis strains. In total, among the 62 isolates, 56 different patterns were observed. 50 strains had unique RFLP patterns (89%) and 12 (11%) revealed patterns that were found among at least 1 other isolate. Spoligotyping of 97 isolates resulted in 42 different patterns, of which 72% were found in 15 clusters. 14 (29%) out of 48 investigated isolates were resistant to 1 or more antituberculosis drugs and 57% of the resistant isolates were isolated from Afghan immigrants. Ten percent of the isolates represented the Beijing genotype, including 4 of the 14 (36%) resistant strains. Three of these resistant Beijing strains were isolated from Afghan patients. IS6110-RFLP typing could be useful for studying the epidemiology of tuberculosis in Iran. IS6110 patterns were polymorphic and the average IS6110 copy number was high.

The exon 1 polymorphism (49A/G) of ctla-4 gene corresponds to an amino acid exchange (threonine to alanine) in the leader peptide of the expressed protein. There are reports concerning the higher level of G allele in subjects with various autoimmune diseases, which has resulted in the hypothesis that CTLA-4 may play a role in regulating selftolerance by the immune system and in the pathogenesis of autoimmune disorders. This study was undertaken to investigate the correlation of exon 1 (49A/G) polymorphism in the ctla-4 gene and breast cancer. The ctla-4 49A/G polymorphism was studied in 197 women with primary breast cancer and 151 age/sex matched normal individuals. The results indicated a significant difference between frequency of ctla-4 genotypes in patients and controls. The frequency of GG genotype was significantly decreased in breast cancer patients compared to controls (4.6% v.s. 12.6%, P = 0.012). There was also a significant positive correlation between tumor size and the existence of AA genotype in patients (P = 0.016). In addition, a positive correlation between AA genotype and lymph node involvement was observed (P = 0.042). The observed decrease in the frequency of GG genotype in the breast cancer patients is contrary to the frequently reported increase of GG genotype in autoimmune diseases. In addition, the data implies that polymorphism of ctla-4 exon 1 contributes in tumor progression.

Stromal cell-Derived Factor-1 (SDF-1, CXCL12) is one the ELR K CXC angiogenic chemokines. It contributes to hematopoiesis and lymphocyte trafficking. SDF-1 and its exclusive receptor, CXCR4, are reported to play important roles in tumor growth, angiogenesis and metastasis of different types of tumors such as breast, lung, prostate and pancreatic cancers. SDF-1 gene polymorphism, known as SDF1-3 0 A, has been investigated in HIV-1 infection and the incidence of breast cancer. This investigation was aimed to study the frequency of SDF1-3 0 A mutation in Iranian women with breast cancer. Results showed that the frequency of AA and AG genotypes was higher among patients, while the frequency of GG genotype was lower compared to the controls. Thus AA and AG genotypes of SDF-1 may be considered as factors increasing the susceptibility of Iranian women to breast cancer.

Some of the authors of this publication are also working on these related projects: a) Memory CD4+ T cell subsets show differential responses to HIV latency reversing agents View project 3. PD-1+ and LAG3+ CD4+ T-cells drive HIV persistence by regulation of T-cell homeostasis through distinct mechanisms View project

CITATIONS 24 READS 30 8 authors, including: Some of the authors of this publication are also working on these related projects: a) Memory CD4+ T cell subsets show differential responses to HIV latency reversing agents View project 3. PD-1+ and LAG3+ CD4+ T-cells drive HIV persistence by regulation of T-cell homeostasis through distinct mechanisms View project

CTLA-4 is a homeostatic regulator of T cell activation and is believed to play a critical role in peripheral tolerance. The contribution of CTLA-4 gene variants to type 1 diabetes has been analyzed in several ethnic groups. In this study, the association of CTLA-4 +49 A/G polymorphism with type 1 diabetes was investigated in Iranian patients. One hundred and nine patients and 331 healthy subjects formed the studied populations. CTLA-4 A/G polymorphism at position 49 in exon 1 was identified using PCR-SSCP and PCR-RFLP methods. Patient numbers with A/G, A/A and G/G genotypes were 78 (71.5%), 21 (19.3%) and 10 (9.2%) while in healthy controls, these were 149 (45%), 146 (44.2%) and 36 (10.8%), respectively. A significant decrease in the frequency of the A/A genotype was observed in the diabetes group (p = 0.000004). In diabetic subjects, the allele frequency of G was also higher than in controls (45% versus 33.4%, p = 0.00269). The differences in the genotypes and the alleles were greater in patients with younger age of diabetes onset (age 15 years) compared with controls (p = 0.000001 and p = 0.000579, respectively). The distribution of the CTLA-4 polymorphism between patients did not show any significant difference according to diabetic ketoacidosis at onset. In conclusion, the result of this study in combination with the previous reports of other ethnic populations showed that CTLA-4 +49 A/G polymorphism confers genetic susceptibility to type 1 diabetes, particularly in younger individuals.

Host genetic control of HIV infection involves certain polymorphisms of some chemokine receptor genes that are associated with susceptibility and progression of HIV-1 infection. Recent data suggest that two important polymorphisms in CCR2 and CCR5 chemokine receptors, CCR5 32 and CCR2-64I, prevent HIV transmission and delay disease progression. In this study allele and haplotype frequencies of the CCR5 32 and CCR2-64I mutations were determined in southern Iranian normal population using PCR and PCR restriction fragment length polymorphism (PCR-RFLP) assays. Allele frequencies and the fit to the Hardy-Weinberg equilibrium (HWE) were evaluated by Arlequin population genetic software. Frequencies of CCR5 32 and CCR2-64I alleles were 0.0146 and 0.1221, respectively. Moreover, higher and lower haplotype frequencies in 341 normal individuals were CCR2/CCR5 (0.8636) and CCR5/CCR2-64I (0.1217), respectively. Only one case with CCR5 32/CCR2-64I haplotype was found among the studied normal population. This data is the first finding on the frequencies of CCR5 32 and CCR2-64I alleles in Iranian population. Results of the present study suggest that low frequency of CCR5 32 allele may be related to higher genetic susceptibility to the HIV-1 infection in Iranians. Results also suggest that the CCR2-64I mutation is sufficiently common in Iranians and may be associated with slower HIV infection progression in Iran.

Beta-thalassemia is among the most common genetic disorders in the world and in Iran, with widespread occurrence. A cross-sectional study on 648 beta-thalassemia patients in Shiraz, Iran was carried out to determine the demography of beta-thalassemia major in Shiraz city, Fars province, Iran and also the rate of consanguinity and the significance of pre-marriage counseling in decreasing familial marriages and consequently preventing this autosomal recessive genetic disease. All interviewed patients had thalassemia major and their age, sex, and the consanguinity between parents were recorded. 40.6% of beta-thalassemia patients were outcomes of first-cousin marriages. Comparison of the percentages of familial marriages (consanguinity) between parents of beta-thalassemia patients and a sample of normal population, revealed a statistically significant difference (p< 0.00001). A nonstatistically significant difference was observed between male (53.5%) and female (46.5%) thalassemia patients. Comparison of data with the situation in 22 years ago revealed a 16.4% decrease in familial marriages among thalassemic families, however, more education and awareness of young women and men about the increased risk of beta-thalassemia after familial marriage through pre-marriage counseling is still necessary.

Iranian population with an Indo-European origin is one of the oldest populations in the world. Historical evidence suggests the close similarity in the origin of Iranian, European and north Indian population. However, there are few anthropological and genetic evidences on this subject. This study, which is the first report from Iran, was performed to investigate the genetic origin of Iranian population using a polymorphism in Cystathionine beta synthase (CBS) gene known as 844INS68bp in this respect, genomic DNA was extracted from the whole blood of 480 healthy normal blood donors referred to Fars Blood Transfusion Center, using a salting out method. The fragment containing 844INS68bp was amplified, the normal fragment was 174 bp and the fragment containing the insertion was 242 bp in length. Results indicated that 418 (87.08%) out of 480 individuals had a normal (N/N) genotype, 59 (12.29%) individuals were heterozygote (N/I) and 3 (0.63%) had homozygote a mutated genotype (I/I). The total frequency of 844INS68bp allele was found 6.8% which is similar to with the reported in White Caucasians. Comparison of the genotype of this study with the polymorphism in other populations revealed that Southern Iranian population has a great similarity with other Caucasians populations' especially South Italy and North America while differed from East Asian and African populations. These results are in agreement with the result of other studied polymorphisms. Therefore, despite the great admixture of Iranian population with the neighboring non-Caucasian populations during the time, Iranian population still share a genetic background with other Caucasian populations.

Background: A soluble form of HER-2/neu extracellular domain (sHER-2) is reported to be released in the sera of metastatic breast cancer patients. Objective: To measure the level of sHER-2 in sera of 115 breast cancer patients. Methods: Serial samples of 27 patients with metastasis, 18 non-metastatic patients, 15 patients in stage 0/I and 14 patients with accompanying benign breast disease were also included in this study. Results: No significant difference was observed between sHER-2 level in the pre-operative sera of breast cancer patients and that of healthy individuals. Only 8 out of 27 patients whom later developed metastasis showed elevated levels of sHER-2 in their first serum sample. However, a trend of increase in the level of sHER-2 was observed in 14 (51.8%) of 27 metastatic sera before clinical diagnosis of the metastasis. A significant association between sHER-2 positive status and vascular invasion of the tumor was observed (P = 0.02). In addition, significant correlation of sHER-2 level with CEA (highest r = 0.74) and CA 15.3 (highest r = 0.74) tumor marker levels in the serial sera were observed. The mean time from sHER-2 positivity to tumor metastasis was calculated to be 98 days (range = 29-174).

The HER-2/neu gene is located on chromosome 17q21 and encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity reported to be released in soluble form in various malignancies. Objective: To evaluate the clinical significance of soluble Her-2/neu as a diagnostic marker in lung cancer. Methods: Serum levels of soluble HER-2/neu were measured in 43 patients with lung cancer and 42 age and sex matched controls by an enzyme immunoassay method. Results: Mean serum level of soluble Her-2/neu in cancer patients was 6.07±10.37 ng/ml which was significantly higher than the control group (P < 0.05). Cigarette smoking had no effect on the level of soluble HER-2/neu. A cut off value of 6.1ng/ml revealed a high specificity (95%) for diagnosis of lung cancer, but a very low sensitivity (14%). Conclusion: The results of this study show an increased level of soluble HER-2/neu in the sera of lung cancer patients with a high specificity but low sensitivity for diagnosis of lung cancers.

Objective: To investigate the placental transfer of RSV-specific IgG in Iranian mothers. Methods: The antibodies were measured in sera of 146 mother/newborn pairs using a commercially available indirect Enzyme Linked Immunosorbent Assay (ELISA). The studied subjects were among healthy pregnant women who attended to the Zeinabieh Hospital of Shiraz University of Medical Sciences in a one year period. Results: A highly significant correlation was observed between RSV-specific IgG in newborns and mothers (r = 0.88). However, mean RSV-specific IgG antibodies in neonates was significantly higher than that of their mothers (P = 0.019). In addition, the mean cord/maternal ratio of RSV-specific IgG was detected to be 1.27 ± 0.60. Maternal blood group, age, parity, previous abortions and neonatal gestational age had no correlation with placental transfer of RSV-specific IgG antibodies. Conclusion: Our finding demonstrates that placental transfer of RSV-specific IgG antibodies is an active process and the main factor that influences this transfer is maternal concentration of these immunoglobulins.

Vitiligo is an acquired skin disorder that selectively destroys melanocytes in epidermis with an unknown etiology. Objective: To investigate the exon 1 A49G polymorphism of cytotoxic T lymphocyte antigen-4 (ctla-4) gene in vitiligo patients. Methods: The A49G polymorphism was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method in 101 patients and 208 normal healthy age/ethnicity matched individuals. Results: The frequencies of heterozygote genotypes in patients and controls were found to be 42 (41.6%) of 101 and 85 (40.9%) of 208, respectively. The frequencies of homozygote A and G genotypes were 49 (48.5%) and 10 (9.9%) in 101 patients, whereas, these frequencies in 208 control individuals were 103 (49.5%) and 20 (9.6%), respectively. There was no significant difference between the genotype (P = 0.98) and allele (P = 0.86) frequencies of A49G polymorphism in patients and normal healthy individuals. Conclusion: Our results indicate that in contrast to several immune mediated disorders, there is no association between ctla-4 A49G gene polymorphism and vitiligo.

CD1 molecules might contribute to anti-tumor immune response by presentation of tumor-derived lipid and glycolipid antigens to T cells and NKT cells. Polymorphisms in CD1 genes have been suggested to modify ligand binding of CD1 molecules and thereby change the antigen presenting ability of these molecules. The aim of this study was to investigate the exon 2 polymorphisms of CD1a and CD1d in several high incident cancers in Iran. For this purpose, 201 female breast cancer patients and 207 healthy women, 64 lung cancer patients and 95 healthy individuals and 109 patients with colorectal cancer and 109 healthy controls were recruited to this study. Using PCR-SSP method, no significant correlation was found in genotype and allele frequencies of CD1a between all three studied groups and their control counterparts. Moreover, a dominant frequency of CD1d 01 (A) allele was observed in the majority of studied individuals. No significant association between the CD1 polymorphisms and prognostic factors in breast, lung and colorectal cancers was detected. Our results highlight the conserved nature of CD1 genes and may point to the immuoregulatory functions of CD1 molecules in cancer that can be exerted through fine tuning of NK, T and NKT cells.