Mohammad Reza Haghshenas; Seyed Reza Hosseini; Mohammad Javad Fattahi; Mahyar Malekzadeh; Ali Ariafar; Abbas Ghaderi
Abstract
Background: Interleukin-37 (IL-37) is a recently described cytokine that emerges as a natural inhibitor of inflammatory and immune responses. However, IL-37 has not yet been investigated in bladder cancer, and its biological role is unknown. Objective: The purpose of this study was to investigate IL-37 ...
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Background: Interleukin-37 (IL-37) is a recently described cytokine that emerges as a natural inhibitor of inflammatory and immune responses. However, IL-37 has not yet been investigated in bladder cancer, and its biological role is unknown. Objective: The purpose of this study was to investigate IL-37 serum levels in patients with bladder cancer and determine whether they were linked to the patients' pathological characteristics. Methods: IL-37 serum levels were measured using a commercial ELISA kit in 60 patients with transitional cell carcinoma (TCC) of the bladder (mean age: 64.55±12.93) and 50 healthy controls (mean age: 62.94±12.69). Non-parametric tests were used for statistical comparisons, and the Cohen's d effect size was calculated to evaluate the practical and clinical significance of the results. Results: Our findings indicated an increasing trend in IL-37 serum levels in patients with TCC (42.77±3.36 pg/ml) in comparison with controls (40.51±7.32 pg/ml, p=0.09). However, IL-37 serum levels were found to be significantly higher in male patients (44.72±3.81 pg/ml) and patients aged ≥70 (46.92±6.77 pg/ml) in comparison with male controls (29.96±3.30 pg/ml, p=0.026) and controls aged ≥70 (23.62±4.43 pg/ml, p=0.009). In comparison to similar controls, Cohen's d effect size for patients aged ≥70 years was found to be 0.90. Conclusion: The findings reveal a higher serum level of IL-37 in patients with TCC, which might be clinically associated with immunosuppression and tumor growth. However, this is a preliminary study, and more research on the biological role of IL-37 and its potential therapeutic effects in bladder cancer is required.
Mohsen Arabpour; Atri Ghods; Mahmoud Shariat; Abodl-Rasoul Talei; Fereshteh Mehdipour; Abbas Ghaderi
Abstract
Background: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity. Objective: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters. Methods: ...
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Background: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity. Objective: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters. Methods: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti‒CD19 and anti‒4-1BBL antibodies and subjected to flow cytometry. Results: 4-1BBL expression was detected on 2.8 ± 1.7% of unstimulated B cells, while 27.4 ± 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER‒ or PR‒ patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage. Conclusions: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.
Mahboobeh Razmkhah; Nadieh Abedi; Ahmad Hosseini; Mohammad Taghi Imani; Abdol-Rasoul Talei; Abbas Ghaderi
Volume 12, Issue 1 , March 2015, , Pages 1-15
Abstract
Background: Adipose derived stem cells (ASCs) provoke the accumulation and expansion of regulatory T cells, leading to the modulation of immune responses in tumor microenvironment. Objective: To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation. Methods: Peripheral ...
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Background: Adipose derived stem cells (ASCs) provoke the accumulation and expansion of regulatory T cells, leading to the modulation of immune responses in tumor microenvironment. Objective: To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation. Methods: Peripheral blood naïve CD4+ T cells were co-cultured with ASCs derived from breast cancer or normal breast tissues. In separate cultures peripheral blood naïve CD4+ T cells were exposed to the culture supernatants of ASCs. Results: Generation of CD4+CD25+Foxp3+ and CD4+CD25- Foxp3+ Treg subsets was observed after coculture of naïve CD4+ T cell with either ASCs or the related supernatant. The percentage of CD4+CD25+Foxp3+ cells increased after exposing naïve CD4+ T cells to both ASCs and their supernatants while augmentation of CD4+CD25-Foxp3+ subset mostly depended on the presence of ASCs. Similarly, upregulation of FoxP3 molecule was more significant in condition of cell to cell contact. IL-4 and IL-10 were up-regulated in the cocultured naïve CD4+ T cells after exposure to ASCs/supernatant while IFN-γ was down-regulated in the presence of ASCs. Conclusion: Accordingly, ASC may act as one of the major players in tumor site with immunomodulatory effects, which may mostly be carried out through direct cellcell interaction.
Zahra Faghih; Somayeh Rezaeifard; Akbar Safaei; Abbas Ghaderi; Nasrollah Erfani
Volume 10, Issue 4 , December 2013, , Pages 193-204
Abstract
Background: CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile. Objective: To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer. Methods: ...
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Background: CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile. Objective: To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer. Methods: Single cell suspensions were obtained from TDLNs of 42 patients with breast cancer. Staining of the cell surface markers and intracellular cytokines was performed using appropriate fluorochrome-conjugated antibodies. The data was acquired on a four-color flow cytometer and was analyzed by CellQuestPro software package. The percentages of different CD8+ cell subtypes (Tc1, Tc2 and Tc17) were quantified in CD8+ T lymphocytes. The comparison was made between LN+ versus LN- patients, as well as patients in different clinico-pathological status. Results: The percentage of Tc1, Tc2 and Tc17 subsets were not significantly different between LN+ and LN- patients. Despite no difference in the percentages of Tc1 cells in LN+ patients with infiltrative ductal carcinoma (IDC), the mean expression of IFN-γ by Tc1 cells decreased significantly in comparison to LN- patients. On the other hand, the percentages of Tc2 and Tc17 effector subsets were increased in advanced stages (p=0.018 and p=0.009, respectively). Conclusion: As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages (Tc2 and Tc17) in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-γ by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.
Nasrollah Erfani; Faezeh Moghaddasi-Sani; Mahboubeh Razmkhah; Mohammad Reza Haghshenas; Abdolrasoul Talaei; Abbas Ghaderi
Volume 9, Issue 4 , December 2012, , Pages 226-233
Abstract
Background: CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known ...
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Background: CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known to be associated with poor prognosis. Objective: To investigate the association of a single nucleotide polymorphism (SNP) in CCL22 gene; 16C/A (rs4359426; Asp2Ala), with susceptibility to breast cancer in a sample of Iranian population. Methods: 161 patients with pathologically confirmed breast carcinoma (mean age 49.3 ± 11.5 yrs) and 178 agematched healthy women (mean age: 49.3 ± 12.9 yrs) were studied. CCL22 genotypes were investigated by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Data was verified by direct automated sequencing. Arlequin analysis showed no deviation from Hardy-Weinberg equilibrium. Results: The most frequent genotype in both patient and control groups was wild type CC genotype with frequency of 146 out of 161 (90.7%) among patients and 153 out of 178 (86.0%) in control group (p=0.24). The frequency of CA genotype was 15 (9.3%) and 23 (12.9%) in patients and controls, respectively (p=0.38). No AA genotype was observed among patients but this genotype was observed with the frequency of 2 out of 178 (1.1%) in control subjects. The minor allele frequency (MAF) was 0.07 in the population. Conclusion: No correlation was found between the investigated genotypes and clinicopathological characteristics of the patients. Conclusively, results of this investigation do not support the association of 16C/A SNP (rs4359426; Asp2Ala) in CCL22 gene with susceptibility to, and progression of, breast cancer in Iranian population.
Nasrollah Erfani; Mohammad Reza Haghshenas; Mohammad Ali Hoseini; Seyed Basi Hashemi; Bijan Khademi; Abbas Ghaderi
Volume 9, Issue 3 , September 2012, , Pages 188-198
Abstract
Background: Variations in Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) affect the expression and function of this protein. Objective: We aimed to investigate the association of +49 A/G (rs231775), +1822 C/T (rs231779) and +6230 A/G (CT60, rs3087243) genetic variations, as well as the merged haplotypes in ...
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Background: Variations in Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) affect the expression and function of this protein. Objective: We aimed to investigate the association of +49 A/G (rs231775), +1822 C/T (rs231779) and +6230 A/G (CT60, rs3087243) genetic variations, as well as the merged haplotypes in CTLA-4 gene with susceptibility to, or progression of head and neck cancer. Methods: Eighty patients with confirmed head and neck (HN) cancer (age 54.9 ± 16.1 years) and 85 healthy age/sexmatched controls (age 56.3 ± 12.4 years) were enrolled in the study. Genotypes were investigated by the PCR-RFLP method. Arlequin software package was used to check for Hardy-Weinberg equilibration, and to estimate the haplotypes. Results: At position +6230 A/G (CT60), AA genotype, as well as A allele was significantly decreased in patients with HN cancers than controls (18.8% vs. 40.7%, p=0.004; odds ratio=0.34, and 46.3% vs. 61.7, p=0.007; odds ratio=0.53%, respectively). Nearly the same results were obtained when we compared the subgroup of patients with squamous cell carcinoma of the HN (SCC-HN) with control subjects. The frequencies of genotypes and alleles at other positions were not significantly different between patients and controls, however ACG, GTA and GCA haplotypes emerged from three investigated loci occurred with significantly more frequencies in patients (p<0.0001), while ACA and GTG haplotypes were more frequent among controls (p<0.0001). Significant differences of haplotypes, genotypes and alleles frequencies resisted the Bonferroni correction. Conclusion: Our results suggest that CT60 A allele, as well as ACA and GTG haplotypes in CTLA-4 gene may have protective roles against HN cancer in Iranian population, while ACG, GTA and specially GCA haplotypes may render susceptibility.
Abbas Ghaderi
Volume 8, Issue 3 , September 2011, , Pages 127-149
Abstract
Gene association studies are less appealing in cancer compared to autoimmune diseases. Complexity, heterogeneity, variation in histological types, age at onset, short survival, and acute versus chronic conditions are cancer related factors which are different from an organ specific autoimmune disease, ...
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Gene association studies are less appealing in cancer compared to autoimmune diseases. Complexity, heterogeneity, variation in histological types, age at onset, short survival, and acute versus chronic conditions are cancer related factors which are different from an organ specific autoimmune disease, such as Grave’s disease, on which a large body of multicentre data is accumulated. For years the focus of attention was on diversity and polymorphism of major histocompatibility complex in respect to human diseases specially the autoimmune diseases, but in recent years, access to other human gene sequences prompted investigators to focus on genes encoding the immune regulatory proteins such as the co-stimulatory, adhesion molecules, cytokines and chemokines and their receptors. Among them, CTLA4 (CD152) has been in the centre of attention for its pivotal role in autoimmunity and cancer. Although not fully understood, CTLA4 with no doubt plays an important role in the maintenance of the immune response by its expression on activated and regulatory T cells. CTLA4 (Gene ID:1493, MIM number:123890) has many variants and polymorphic forms, some present in regulatory positions, some in 3' UTR and the most important one in the leader sequence (+49 A/G). As a pivotal regulatory element of the immune responses magnitude, CTLA4 could be considered as a two-blade knife, for which only the optimal expression ensures an effective, but at the same time, safe immune response. It can accordingly be speculated that CTLA4 alleles associated with extraordinary expression could make a person more susceptible to tumor growth and/or progression. On the other hand, alleles associated with a compromised CTLA4 expression/function may accelerate the formation and/or manifestation of inflammatory autoimmune disorder. I hypothesized a spectrum of the functional dichotomy of CTLA4 SNPs diverging from autoimmunity to cancer. To examine these hypotheses, results from previously published investigations on CTLA4 polymorphisms together with the work done by our own group are discussed in details. Because the most published data are about the polymorphism at position +49, I concentrated on this position; however the data regarding other SNPs are also included for comparison. To support the significance of CTLA4 gene variation in these two major human diseases evidences from organ transplantation are also included. As will be discussed in the manuscript, our work and reports by others from a normal population perspective support the hypothesis that individuals inheriting a GG genotype at position +49, for which lower CTLA4 expression has been extensively suggested, are more susceptible for developing autoimmune disorders and those with AA genotype, with an existence of a state of self-tolerance, may have a higher chance of developing cancer. CTLA4 SNPs may accordingly be considered as a crucial element, along with other known or yet unknown mechanisms, in keeping the immune balance in predisposed individuals to cancer and autoimmunity. Although an spectrum line can be drawn between autoimmunity and cancer by considering published data regarding CTLA4 +49 polymorphism, the extreme functional dichotomy of this SNP appears to be more complex and difficult to understand, but there is no doubt that the future investigations will resolve most ambiguities.
Neda Mousavi Niri; Mansooreh Jaberipour; Mahboobeh Razmkhah; Abbas Ghaderi; Mojtaba Habibagahi
Volume 6, Issue 4 , December 2009, , Pages 186-194
Abstract
Background: Several studies have demonstrated the immunosuppresive effects of mes-enchymal stem cells (MSCs) in allogeneic or mitogenic interactions. Cell-cell contact inhibition and secretion of suppressive soluble factors have been suggested in this re-gard. Objective: To investigate if adipose derived ...
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Background: Several studies have demonstrated the immunosuppresive effects of mes-enchymal stem cells (MSCs) in allogeneic or mitogenic interactions. Cell-cell contact inhibition and secretion of suppressive soluble factors have been suggested in this re-gard. Objective: To investigate if adipose derived MSCs could inhibit Jurkat lym-phoblastic leukemia T cell proliferation during coculture. Methods: Adherent cells with the ability of cellular growth were isolated from normal adipose tissues. Initial charac-terization of growing cells by flow cytometry suggested their mesenchymal stem cell characteristics. Cells were maintained in culture and used during third to fifth culture passages. Jurkat or allogeneic peripheral blood mononuclear cells (PBMCs) were la-beled with carboxy fluorescein diacetate succinimidyl ester and cocultured with increas-ing doses of MSCs or MSC culture supernatant. Proliferation of PBMCs or Jurkat cells under these conditions was assessed by flow cytometry after 2 and 3 days of coculture, respectively. Results: Results showed the expression of CD105, CD166 and CD44, and the absence of CD45, CD34 and CD14 on the surface of MSC like cells. Moreover, ini-tial differentiation studies showed the potential of cell differentiation into hepatocytes. Comparison of Jurkat cell proliferation in the presence and absence of MSCs showed no significant difference, with 70% of cells displaying signs of at least one cell division. Similarly, the highest concentration of MSC culture supernatant (50% vol/vol) had no significant effect on Jurkat cell proliferation (p>0.6). The same MSC lots significantly suppressed the allogeneic PHA activated PBMCs under similar culture conditions. Conclusion: Using Jurkat cells as a model of leukemia T cells, our results indicated an uncertainty about the suppressive effect of MSCs and their inhibitory metabolites on tumor or leukemia cell proliferation. Additional systematic studies with MSCs of differ-ent sources are needed to fully characterize the immunological properties of MSCs be-fore planning clinical applications.
Shirin Farjadian; Mehrdad Lotfazar; Abbas Ghaderi
Volume 5, Issue 3 , September 2008, , Pages 171-176
Abstract
Background: Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and early development of aggressive pe-riodontitis. Although cathepsin C (CTSC) gene mutations have been established in about 70-80% of PLS patients, it is assumed that the ...
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Background: Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and early development of aggressive pe-riodontitis. Although cathepsin C (CTSC) gene mutations have been established in about 70-80% of PLS patients, it is assumed that the patients may have dysfunctioning of immune defense mechanisms. Objective: To assess the association of HLA class II genes and PLS. Methods: HLA class II genes were typed in nine Iranian PLS patients and their family members and the results were compared to 816 Iranian healthy sub-jects. Results: The results of this study revealed that DRB1*0101 and DRB1*0301 al-leles were more frequent in PLS patients than in normal controls. However, there was no significant difference between PLS patients and normal controls. Moreover, the same haplotypes and genotype combinations were also observed in some patients and their healthy siblings. Conclusion: The results of this study showed no strong association between HLA class II alleles and PLS.
Sedigheh Sharifzadeh; Helmout Modjtahedi; Mahmood Jedi Tehrani; Abbas Ghaderi
Volume 4, Issue 4 , December 2007, , Pages 206-214
Abstract
Background: Lung carcinoma is a multiple type cancer comprising of small cell and non-small cell carcinomas (NSCLC). For therapeutic and diagnostic purposes, serum monoclonal antibodies have been produced against lung cancer. Objective: To charac-terize a murine monoclonal antibody (ME3D11) reactive ...
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Background: Lung carcinoma is a multiple type cancer comprising of small cell and non-small cell carcinomas (NSCLC). For therapeutic and diagnostic purposes, serum monoclonal antibodies have been produced against lung cancer. Objective: To charac-terize a murine monoclonal antibody (ME3D11) reactive with human NSCLC. Methods: A murine monoclonal antibody (ME3D11) reactive with human NSCLC was selected after immunization of BALB/c mice with a human large cell carcinoma with neuroen-docrine differentiation, and was tested by immunofloursence staining and Western blot analysis. Results: Our study showed that the antigen recognized by ME3D11 antibody was a cell surface antigen of 170kDa. This antigen is expressed on the cell surface of all NSCLC and a few carcinoma cell lines. In contrast, this antigen is neither expressed on the cell surface of human sarcoma, nor on the hematopoietic and normal cell lines. This anti-body had no effect on spontaneous proliferation of Mehr-80 cell line in vitro. Conclusion: High degree of binding of this monoclonal antibody to NSCLC and some other carci-noma cells warrants further studies on its potential use in diagnosis and therapy of can-cer by conjugation to drugs, toxins or radionuclides.
Shirin Farjadian; Abbas Ghaderi
Volume 4, Issue 2 , June 2007, , Pages 85-93
Abstract
Background: Anthropological studies based on highly polymorphic HLA genes pro-vide useful information for bone marrow donor registry, forensic medicine, disease as-sociation studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases. Objective: This study was ...
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Background: Anthropological studies based on highly polymorphic HLA genes pro-vide useful information for bone marrow donor registry, forensic medicine, disease as-sociation studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases. Objective: This study was designed to investigate the genetic relationship of Iranian Arabs and Jews using HLA-class II genetic diversity Methods: HLA-DRB1, DQA1, and DQB1 allele frequencies and haplotypes were determined in 134 Iranian Arabs from two different communities and 91 Iranian Jews using PCR/RFLP and PCR/SSP methods. Results: Neighbor-joining analyses showed a closer genetic relationship between Iranian Arabs and Iranian Jews than between either Iranian Arabs and Middle Eastern Arabs or Iranian Jews and other Jews. The results of AMOVA test also revealed no significant difference between these populations and other Iranians. Conclusion: It seems that, Iranian Arabs are originally from the Iranian gene pool and speak Arabic due to their encounter with Arabs. Iranian gene flow to im-migrant Jews followed by their expansion in this country may also explain the close ge-netic relationship among different Iranian ethnic groups.
Abolhassan Faramarzi; Azra Shamsdin; Abbas Ghaderi
Volume 3, Issue 4 , December 2006, , Pages 187-191
Abstract
Background: Tonsils and adenoids are involved in both local immunity and immune surveillance for the development of immune defense mechanisms. A number of investigators have found decreased immunoglobulin levels after adenotonsillectomy while others have failed to find significant changes. The effects ...
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Background: Tonsils and adenoids are involved in both local immunity and immune surveillance for the development of immune defense mechanisms. A number of investigators have found decreased immunoglobulin levels after adenotonsillectomy while others have failed to find significant changes. The effects of adenotonsillectomy on the cellular immunity of children have not been investigated extensively. Objective: To observe the change in humeral and cellular immune systems before and after operation in patients undergoing adenotonsillectomy. Methods: The study comprised 102 patients; all of the patients underwent adenotonsillectomy. The levels of IgG, IgA, and IgM were measured for humoral immunity and the percent of CD7 and CD19 positive cells were determined in blood samples taken from these patients 24 hours before operation and also 2 and 8 weeks after the operation. The results were subjected to statistical analysis. Results: The present study shows that the serum level of IgA would rise few weeks after the operation. Changes in the IgM and IgG level were not statistically significant postoperatively. In addition, no significant change was detected in B lymphocyte count before and after adenotonsillectomy. In our study, there was a slight decrease in the T lymphocyte count in the early stage of post operation, which returned to normal preoperative value after 8 weeks . Conclusion: Several immune system parameters maintain its normal status several weeks after adenotonsillectomy.
Shirin Farjadian; Abbas Ghaderi
Volume 3, Issue 3 , September 2006, , Pages 106-113
Abstract
Background: HLA genes are highly polymorphic and certain alleles are frequent only in specific populations. Therefore, HLA is a unique tool for studying the genetic relationship between different populations. Iranians are ethnically diverse people and one of the major ethnic groups in Iran is Lur population ...
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Background: HLA genes are highly polymorphic and certain alleles are frequent only in specific populations. Therefore, HLA is a unique tool for studying the genetic relationship between different populations. Iranians are ethnically diverse people and one of the major ethnic groups in Iran is Lur population inhabiting along the central and southern parts of Zagros Chain Mountain. Objectives: Genetic relationship among three Lur subpopulations was investigated based on HLA class II profiles. Methods: HLA typing was performed using PCR/RFLP and PCR/SSP methods in 154 individuals from three Lur subpopulation living in Luristan, Kohkiloyeh/ Boyerahmad, and Chahar-Mahal/ Bakhtiari. Results: The most common DRB1 allele in Lurs of Luristan and Kohkiloyeh/ Boyerahmad was *1103=4 while DRB1*0701 was the most common allele in Bakhtiaris. DQA1*0501 and DQB1*0301 were the most frequent alleles and DRB1*1103=04-DQA1*0501-DQB1*0301 was the predominant haplotype in the three studied subpopulations. Neighbor-joining tree based on Nei's genetic distances and correspondence analysis according to DRB1, DQA1, and DQB1 allele frequencies showed a close genetic relationship between Lurs of Luristan and Lurs of Kohkiloye/ Boyerahmad and they were well separated from Bakhtiaris. The results of AMOVA revealed no significant difference between the three studied groups of Lurs and other major ethnic groups of Iran. Conclusion: The results of this study revealed that Bakhtiaris were genetically far from the two other Lur subpopulations. Despite a probable common ancestor, this genetic difference might be explained by Bakhtiaris admixture with other Zagros inhabitants due to their nomadic life style.
Seyyed Mohammad Ali Ghayumi; Kambiz Aghasadeghi; Mehrnoosh Dorouchi; Abbas Ghaderi
Volume 3, Issue 2 , June 2006, , Pages 61-65
Abstract
Background: 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 ...
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Background: 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.
Mehrnoosh Doroudchi; Abdolrasoul Talei; Helmout Modjtahedi; Alamtaj Samsami Dehaghani; Abdol Mohammad Pezeshki; Hilary Thomas; Abbas Ghaderi
Volume 2, Issue 4 , December 2005, , Pages 191-200
Abstract
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 ...
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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). Conclusion: Our results indicate that a relatively high percentage of Iranian patients with breast cancer show an elevated level of sHER-2 in their sera before clinical diagnosis of the tumor metastasis. Therefore, measuring the level of this oncoprotein, not only helps physicians in monitoring the patients during HERCEPTINTM therapy, but also can be helpful in choosing more aggressive treatments at the early satges of tumor metastasis.
Mohammad Javad Fattahi; Abdul Mohammad Pezeshki; Maryam Emad; Mohammad Hosein Lohrasb; Azra Shamseddin; Abbas Ghaderi; Mehrnoosh Doroudchi
Volume 2, Issue 2 , June 2005, , Pages 97-102
Abstract
Background: 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 ...
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Background: 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.
Ezzatallah Basiri; Sadreddin Mohseni Ardehali; Mehrnoosh Doroudchi; Fereidoun Mahboodi; Arsalan Kharazmi; Abbas Ghaderi
Volume 1, Issue 3 , December 2004, , Pages 194-199
Abstract
Background : Production of monoclonal antibodies to Leishmania antigens assists the identification and characterization of these organisms. Objective: Production of monoclonal antibodies against epitopes on the gp63. Methods: Two murine monoclonal antibodies to gp63 were produced and characterized. The ...
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Background : Production of monoclonal antibodies to Leishmania antigens assists the identification and characterization of these organisms. Objective: Production of monoclonal antibodies against epitopes on the gp63. Methods: Two murine monoclonal antibodies to gp63 were produced and characterized. The reactions of both antibodies with soluble leishmanial antigens, purified gp63 and truncated recombinant gp63 molecules were studied by an ELISA assay. These two antibodies reacted with the crude soluble antigens prepared from 4 reference strains of Leishmania, 10 isolates from the patients, purified gp63 and recombinant gp63 molecules. However, no reaction with several non-leishmanial antigens was observed. Reaction of both antibodies with the intact recombinant gp63 and truncated molecules were compared. Results: The results indicated that the two antibodies specifically recognize two different epitopes on the gp63 molecule. Conclusion: Possible applications of such antibodies in searching for immunogenic epitopes are discussed.
Gholamali Yousefi-Pour; Sadegh Izadi; Abbas Ghaderi
Volume 1, Issue 2 , September 2004, , Pages 105-110
Abstract
Objective: To investigate possible immunological humoral correlates in newly diagnosed adult-onset generalized tonic-clonic epilepsy among Iranian patients before and after sodium valproate treatment. Patients and Methods: 72 adult patients with newly diagnosed idiopathic generalized tonic-clonic ...
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Objective: To investigate possible immunological humoral correlates in newly diagnosed adult-onset generalized tonic-clonic epilepsy among Iranian patients before and after sodium valproate treatment. Patients and Methods: 72 adult patients with newly diagnosed idiopathic generalized tonic-clonic epilepsy were recruited. Serum antinuclear antibodies (ANA), anti-cardiolipin antibodies (aCL), anti-dsDNA antibodies, total serum immunoglobulins (IgM, IgG, IgA) and C3 and C4 complements were determined before and after 12 months of therapy with sodium valproate. Similar parameters were also measured in 32 age and sex-matched healthy volunteers. Results: Patients group had a significantly greater level of IgG class aCL (30.6% versus 12.4%, P = 0.004) and anti-dsDNA antibodies (23.9% versus 0%, P = 0.001) when compared with healthy volunteers, however, ANA titre was relatively the same in both groups. Sodium valproate significantly decreased anti-dsDNA antibodiles (P = 0.002), IgM concentrations (P = 0.034), and increased the number of ANA positive patients (P = 0.002). Conclusion: Changes in serum level of autoantibodies in patients with new onset idiopathic generalized convulsion were found to be high. These abnormalities are associated with both seizure disorders per se and also antiepileptic drugs. We suggest that in epileptic patients with an autoimmune basis, administration of anti-epileptic drugs having modulatory effects on immune system should be considered.
Akbar Rajaee; Mohammad Ali Nazarinia; Seyed Modjtaba Hakim; Mitra Amini; Maryam Ayatollahi; Abbas Ghaderi
Volume 1, Issue 2 , September 2004, , Pages 111-117
Abstract
Objective: The clinical value of IgG anticardiolipin antibody in patients with Behçet's disease with or without vascular thrombosis was evaluated. Methods: IgG isotype of anticardiolipin (aCL) antibody was assessed in 40 Behçet's disease (BD) patients with venous or arterial thrombosis, ...
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Objective: The clinical value of IgG anticardiolipin antibody in patients with Behçet's disease with or without vascular thrombosis was evaluated. Methods: IgG isotype of anticardiolipin (aCL) antibody was assessed in 40 Behçet's disease (BD) patients with venous or arterial thrombosis, 40 BD patients without venous or arterial thrombosis and 80 healthy subjects as controls. The levels of IgG aCL were determined by an indirect ELISA method. Color Doppler Sonography, Magnetic Resonance Imaging and conventional angiography were the procedures used for other clinical evaluations. Results: Out of 40 patients with vascular thrombosis, 20(50%) were positive for low to moderate level of IgG aCL. In patients without thrombosis 22(55%) were positive for low to moderate level of IgG aCL while in none (0%) of the healthy subjects the IgG aCL was positive, neither low nor moderate. The number of patients with headache but having a normal cerebral magnetic resonance imaging (MRI), was higher in anticardiolipin positive patients without vascular thrombosis as compared to those with vascular thrombosis, (P = 0.001). Arthritis was noticed in both patents groups. 15% of aCL positive patients without thrombosis had arthritis as compared to none in aCL negative patients without thrombosis (P = 0.02). Conclusion: The results of this study indicate that although the frequency of IgG aCL was found to be higher in Iranian patients with BD in comparison with the previous reports, except in arthritis the observed elevated IgG aCL does not correlate with clinical disease manifestations, or vascular thrombotic complications.
Sara Kashef; Reza Amin; Maryam Ayatollahi; Abbas Ghaderi
Volume 1, Issue 2 , September 2004, , Pages 117-123
Abstract
Background: Antiphospholipid antibody syndrome (APS) can either occur as a primary syndrome or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Anticardiolipin antibody (aCL) of IgG and/or IgM isotype in blood, measured by a standardized ELISA is the most acceptable ...
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Background: Antiphospholipid antibody syndrome (APS) can either occur as a primary syndrome or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Anticardiolipin antibody (aCL) of IgG and/or IgM isotype in blood, measured by a standardized ELISA is the most acceptable laboratory criteria. APS IgG isotype, particularly IgG2 subclass is more strongly associated with thrombosis. Objectives: This study was done to determine the prevalence of IgG aCL and its subclasses in relation to APS symptoms, in a group of juvenile rheumatoid arthritis (JRA) and juvenile systemic lupus erythematosus (SLE) patients. Methods: In this prospective study, 28 JRA and 16 SLE patients, aged 3-18 years, were enrolled. IgG aCL was assayed by standard aCL ELISA. IgG subclasses were also assayed by ELISA on sera with medium to high titers of aCL. ACL assay was performed on at least two occasions for each patient, over 3-6 months period of follow up. Results: 29% (8/28) of JRA patients and 44% (7/16) of SLE patients had aCL. Six of SLE patients displayed APS related manifestations: hemolytic anemia, thrombocytopenia, arterial occlusion, valvular heart disease, livedo reticularis and pulmonary hypertension, but none of them had persistant medium or high titer of aCL. The lack of association of high titer of aCL with APS related symptoms was observed in two patients. The IgG subclasses were primarily IgG1 and IgG3. Conclusion: The prevalence of IgG aCL in this group of pediatric SLE and JRA is not uncommon but it’s relation to clinical manifestations is not clear. IgG1 and IgG3 subclasses were not associated with thrombosis, which is in agreement with previous studies.
Ali Derakhshan; Masoumeh Mohkam; Abbas Ghaderi; Ghamar Hosseini Alhashemi; Mohammad Hossein Fallahzadeh
Volume 1, Issue 1 , June 2004, , Pages 41-47
Abstract
Objective: To evaluate the effect of dialysis and kidney transplantation on serum levels of several tumor markers such as PSA, AFP, CA125, CA19- 9, CA15-3, CEA and to compare with normal age matched controls. Methods: Between September of 2000 and July of 2001, the following tumor markers: PSA, AFP, ...
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Objective: To evaluate the effect of dialysis and kidney transplantation on serum levels of several tumor markers such as PSA, AFP, CA125, CA19- 9, CA15-3, CEA and to compare with normal age matched controls. Methods: Between September of 2000 and July of 2001, the following tumor markers: PSA, AFP, CA125, CA19-9, CA15-3 and CEA were measured by ELISA Method in 29 hemodialyzed patients (group A), in 30 successfully transplanted patients (group B) and in 30 normal volunteers who did not present any clinical symptoms or signs of neoplasia. Results: The serum level of CEA was above the cutoff limit in 6.7% of hemodialyzed patients (group A) but was in the normal range in transplanted and control groups. The level of CEA were significantly higher in hemodialyzed patients in comparison to other groups (p<0.003). Serum levels of AFP and PSA were not significantly different between the three groups (p=0.595 and p=0.545, respectively). Although serum level of CA 19-9 was elevated in 3.3% of hemodialyzed and control group the differences between the three groups were not significant (p=0.507). Serum level of CA 125 was elevated in 13.3% of group A, 13.8% of group B and 6.7% of control group (p=0.347). Serum level of CA15-3 was elevated in 13.3%, 6.9% of group A, B and control group, respectively and the differences were not significant (p=0.156). Conclusion: Hemodialyzed and transplanted patients show a high false positive rate of CEA, CA125 and CA15-3 and may be unreliable for monitoring of malignancies in these patients while other markers evaluated (AFP, PSA and CA 19.9) appear to maintain their specificity in these situations.
Fatemeh Vahedi Darmian; Soheila Joubeh; Mehrnoosh Doroudchi; Behnam Abdollahi; Abbas Ghaderi
Volume 1, Issue 1 , June 2004, , Pages 48-55
Abstract
Background: Vitiligo is a dermatological disorder of unknown etiology with a common incidence in southern Iran. Presence of autoantibodies to melanocyte antigens suggested an autoimmune basis of the disease. Objective: In this study, the presence of rheumatoid factor (RF) in sera and skin biopsies of ...
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Background: Vitiligo is a dermatological disorder of unknown etiology with a common incidence in southern Iran. Presence of autoantibodies to melanocyte antigens suggested an autoimmune basis of the disease. Objective: In this study, the presence of rheumatoid factor (RF) in sera and skin biopsies of vitiligo patients was investigated. Methods: The presence of RF in sera of 35 vitiligo and 32 normal individuals was assessed by an indirect ELISA assay. In addition, the presence of IgM, IgG, and IgA immunoglobulins in the biopsy lesions of patients was also investigated by Immunoperoxidase test. Results: IgM-RF and IgA-RF were detected in sera of 50% and 20% of patients, respectively. Five out of 35 (15%) revealed to produce both IgM and IgA rheumatoid factors. The rheumatoid factor activity of the deposited immunoglobulins at the site of lesion was confirmed by direct immunoperoxidase test. Conclusion: The presence of rheumatoid factors as non organ-specific autoantibodies in vitiligo provides further evidence for the autoimmune etiology of the disease and its pathological importance remains to be elucidated.
