Saeid Taghiloo; Mohsen Soltanshahi; Masoud Aliyali; Siavash Abedi; Hossein Mehravaran; Abolghasem Ajami; Hossein Asgarian-Omran
Abstract
Background: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is recognized for the first time in Wuhan, China. The cytokine storm is a known factor causing major clinical symptoms leading to death in COVID-19 patients. Objective: To investigate and compare the serum levels of ...
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Background: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is recognized for the first time in Wuhan, China. The cytokine storm is a known factor causing major clinical symptoms leading to death in COVID-19 patients. Objective: To investigate and compare the serum levels of different cytokines in COVID-19 patients with different clinical severity. Methods: Concentrations of serum cytokines, including IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, and GM-CSF, were measured in 61 COVID-19 patients and 31 normal controls with ELISA. We investigated the correlation between the levels of these cytokines and clinical severity, CRP level, neutrophil and lymphocyte count in patients with COVID-19. Results: Our data indicated that the levels of IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF, but not IL-10 were significantly increased in COVID-19 patients compared to normal controls. Statistical analysis showed that the level of IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF were higher in severe COVID-19 than those of mild cases. The concentrations of all mentioned cytokines were negatively associated with the absolute count of lymphocytes, and positively correlated with the CRP level and the absolute count of neutrophils. Conclusion: The current study suggests that high levels of various cytokines correlate with the disease severity and immunopathogenesis of COVID-19.
Yousef Khanjari; Morteza Oladnabi; Nafiseh Abdollahi; Ahmad Heidari; Saeed Mohammadi; Alijan Tabarraei
Abstract
Background: Programmed cell death protein 1 (PD-1) is a negative costimulatory molecule with immunomodulatory properties. Recently, PD-1 gene defects have attracted attention in the pathogenesis of SLE. Objective: Here, we assessed the association of PD-1 gene polymorphisms in intron 4 and haplotypes ...
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Background: Programmed cell death protein 1 (PD-1) is a negative costimulatory molecule with immunomodulatory properties. Recently, PD-1 gene defects have attracted attention in the pathogenesis of SLE. Objective: Here, we assessed the association of PD-1 gene polymorphisms in intron 4 and haplotypes with the susceptibility to SLE. Method: Seventy-six SLE patients and 159 healthy controls were included. We screened the polymorphisms by amplifying the intron 4 of the PD-1 gene with the specific primers followed by sequencing. Results: Two distinct SNPs were identified (rs6705653 and rs41386439) within the intron 4 of the PD-1 gene. The AA genotype of +7499 (G/A) SNP was associated with the higher risk of SLE [OR=3.31, 95% CI (1.25-8.76), p-value=0.045], while A allele was identified as a risk allele [OR=1.75, 95% CI (1.10-2.76), p-value=0.015]. However, no significant association was observed between the allele and the genotype frequencies of +7209 (C/T) polymorphic region of the PD-1 gene and susceptibility to SLE. Haplotype analysis showed the significantly higher presence of H2 haplotype (AC; +7499/+7209) [OR=1.70, 95% CI (1.24-2.33), p-value=0.0012] in SLE patients. Conclusion: To the best of our knowledge, this is the first report of the significant association of PD-1 +7499 (G/A) SNP with the SLE susceptibility and the first detection of both polymorphic loci in a population from Iran. However, more investigations are necessary to confirm these findings.
Zahra Rezaei; Gholamreza Pouladfar; Amin Ramezani; Zohreh Mostafavi-Pour; Amin Abbasian; Bahador Sarkari; Bahman Pourabbas
Abstract
Background: Visceral leishmaniasis (VL) can lead to death in more than 95% of cases if left untreated. Accurate and early diagnosis has an important role in reducing mortality rate of this disease. Objective: To express recombinant H2B antigen from an Iranian isolate of Leishmania Infantum and evaluate ...
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Background: Visceral leishmaniasis (VL) can lead to death in more than 95% of cases if left untreated. Accurate and early diagnosis has an important role in reducing mortality rate of this disease. Objective: To express recombinant H2B antigen from an Iranian isolate of Leishmania Infantum and evaluate its efficacy in the diagnosis of VL. Methods: The recombinant H2B antigen was produced in a prokaryotic system, and its efficacy for VL diagnosis was evaluated by ELISA. The serum samples from 80 VL patients, 100 individuals from endemic and non-endemic regions of VL, and 58 non-VL patients were collected. VL cases were confirmed based on the clinical sign, positive IFAT (>64), real time PCR, and response to treatment. Results: The H2B gene sequence of the Iranian L. infantum isolate had about 4% diversity in comparison with the H2B gene of the L. infantum counterpart. ELISA, using the produced H2B recombinant antigen, showed sensitivity of 71.25% (95% CI: 60.05%-80.82%) and specificity of 69.62% (95% CI: 61.81%-76.68%) regarding VL diagnosis. Conclusion: Recombinant H2B antigen expressed in the prokaryotic system had suboptimal performance for the serological diagnosis of VL. It seems that the production and expression of recombinant H2B antigen in a eukaryotic system may enhance the performance of this antigen in the diagnosis of VL in Iran.
Zahra Mehraji; Ali Farazmand; Alireza Esteghamati; Sina Noshad; Maryam Sadr; Somayeh Amirzargar; Mir Saeed Yekaninejad; Aliakbar Amirzargar
Volume 14, Issue 3 , September 2017, , Pages 223-230
Abstract
Background: Graves’ disease (GD), a highly rampant autoimmune disorder of the thyroid gland, is responsible for 60-80% of the clinical cases of hyperthyroidism. Over the past decades, genetic association studies have identified several GD susceptibility loci in CTLA-4, TSHR and major histocompatibility ...
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Background: Graves’ disease (GD), a highly rampant autoimmune disorder of the thyroid gland, is responsible for 60-80% of the clinical cases of hyperthyroidism. Over the past decades, genetic association studies have identified several GD susceptibility loci in CTLA-4, TSHR and major histocompatibility complex regions. The information on the association between the human leukocyte antigens (HLA) and GD among Iranians is scarce. Objective: To identify HLA polymorphisms that might confer susceptibility or protect against GD. Methods: Eighty unrelated patients with a confirmed diagnosis of GD were included in the case group. The control group consisted of 180 unrelated healthy individuals with normal thyroid function tests. The polymerase chain reaction with sequence specific primers (PCR-SSP) method was used for HLA typing. Results: Frequencies of HLA-A*68 (15.6% vs. 4.2%, p=0.004) and B*08 (8.8% vs. 2.5, p=0.030) were significantly higher in patients with GD compared with healthy controls. No patients with GD had HLA-A*33, whereas it was found in 7.0% of the controls (p=0.011). HLA-DQB1*0201 was significantly less frequent among patients with GD (15.6% vs. 26.8%, p=0.040). Additionally, patients with GD were significantly less bound to have HLA-DQA1*0201 (6.2% vs. 15.1%, p=0.045). Concerning allelic distributions, no noticeable difference was found between GD patients with and without Graves’ ophthalmopathy (p>0.05 in all cases). Conclusion: In the Iranian population, HLA-A*68 and -B*08 confer susceptibility to GD, whereas HLA-A*33, -DQB1*0201, and -DQA1*0201 appear to have protective roles.
Behnam Mohammadi-Ghalehbin; Gholam Reza Hatam; Bahador Sarkari; Mehdi Mohebali; Zabih Zarei; Mansoureh Jaberipour; Shahab Bohlouli
Volume 8, Issue 4 , December 2011, , Pages 244-250
Abstract
Background: Visceral leishmaniasis (VL) is caused by Leishmania infantum in Mediterranean basin and is an endemic disease in some parts of Iran. Canines are the main reservoirs of VL in most of the endemic areas. Different serological methods have been introduced for diagnosis of canine visceral leishmaniasis ...
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Background: Visceral leishmaniasis (VL) is caused by Leishmania infantum in Mediterranean basin and is an endemic disease in some parts of Iran. Canines are the main reservoirs of VL in most of the endemic areas. Different serological methods have been introduced for diagnosis of canine visceral leishmaniasis (CVL). Objective: In this survey a Fucose-Mannose Ligand (FML) ELISA, using native L. infantum antigen, was developed and its validity for detection of infected dogs in comparison with direct agglutination test (DAT) and PCR was evaluated. Methods: Blood samples of sixty ownership dogs (≤ 3 years old) were collected from Meshkin-shahr district in Ardabil province, North-west of Iran. Sera were separated for serological assays (DAT and FMLELISA) and the buffy coats were collected for molecular evaluation. Results: Two out of the 60 (3.33%) samples were found to be positive (antibody titer of ≥ 1/320) in DAT while seven of the 60 (11.66%) samples were positive by FML-ELISA. Nine out of 60 (15%) buffy coat samples showed a band about 680 bp indicative of L. infantum in PCR. Three out of 60 dogs had Kala-azar symptoms and were positive by PCR and FML-ELISA, while two of these three dogs had antibody titers >1/320 in their serum samples. The sensitivity and specificity of FML-ELISA for the detection of CVL in both symptomatic and asymptomatic dogs were found to be 77.8% and 100%, respectively. Conclusion: Considering the acceptable sensitivity and high specificity of FMLELISA, use of this serological method can be recommended for epidemiological surveys of CVL.
Roghayeh Rahimi; Ahmad Zavaran Hosseini; Fatemeh Yari
Volume 5, Issue 4 , December 2008, , Pages 207-211
Abstract
Background: HLA-G gene contains 15 alleles including a null allele, HLA-G*0105N. Previous studies have shown that HLA-G*0105N does not encode the complete HLA-G1 or HLA-G5 isoforms but encodes a functional HLA-G protein with the ability to in-hibit NK cell cytolysis. Thus, although the biological functions ...
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Background: HLA-G gene contains 15 alleles including a null allele, HLA-G*0105N. Previous studies have shown that HLA-G*0105N does not encode the complete HLA-G1 or HLA-G5 isoforms but encodes a functional HLA-G protein with the ability to in-hibit NK cell cytolysis. Thus, although the biological functions of HLA-G1 and HLA-G5 proteins are abrogated, other isoforms such as HLA-G2 can replace their roles. Stud-ies on the null allele of HLA-G gene could be useful in understanding the genetic vari-ants of HLA-G alleles in ethnic groups. Objective: The goal of this research was to de-termine the frequency of HLA-G*0105N null allele in Iranian healthy subjects. Meth-ods: The frequency of HLA-G*0105N null allele was evaluated in Iranian healthy sub-jects by PCR-RFLP method. Genomic DNA was isolated from the whole blood of 100 randomly selected, healthy, unrelated Iranian individuals using salting-out technique followed by PCR amplification of the exon 3 of HLA-G gene. PCR products were di-gested with PpUM-1 and the resulted fragments were analyzed using gel electrophore-sis. Results: In this study the restriction enzyme digestion confirmed homozygous HLA-G*0105N null allele for 9 % of the population. Furthermore obtained results indi-cated that the total frequency of HLA-G*0105N null allele was 20 % in the studied population of Iran. Conclusion: The final data analysis showed that the total frequency of this allele in Iranian people was higher than other ethnic groups that have been stud-ied so far.
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.
Shirin Farjadian; Nasrin Kiyanimanesh; Abbas Abbaszadegan; Mehrdad Lotfazar
Volume 4, Issue 4 , December 2007, , Pages 241-245
Abstract
Background: Papillon-Lefevre Syndrome (PLS) is a rare autosomal recessive disorder characterized by diffused palmoplantar keratoderma and severe periodontitis. Increased susceptibility to infections due to impairment of the immune system is considered to be involved in pathoetiology of this disease. ...
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Background: Papillon-Lefevre Syndrome (PLS) is a rare autosomal recessive disorder characterized by diffused palmoplantar keratoderma and severe periodontitis. Increased susceptibility to infections due to impairment of the immune system is considered to be involved in pathoetiology of this disease. Objective: According to the crucial function of HLA molecules in immune responses and association between certain HLA class I alleles and some periodontal or skin diseases, this study was designed to evaluate the relation of HLA class I genes and PLS. Method: HLA class I genes were typed by PCR-SSP (Polymerase Chain Reaction with Sequence Specific Primers) method in eight Iranian PLS patients and 89 healthy controls. Results: The results showed no sig-nificant difference between the patients and controls. Moreover, identical haplotypes or genotypes were also observed among PLS patients and their healthy siblings. Conclu-sion: It seems that further genes are involved in genetic susceptibility to PLS. However the results of this study showed no significant association between HLA class I genes and PLS, molecular analyses of killer immunoglobulin-like receptors (KIRs) and MHC class I chain-related gene A and B (MICA/B) in PLS may clear many obscure points about the genetic factors involved in these diseases.
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.
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.
Ali Asghar Vahidi; Majid Varesvazirian; Ayeh Shamsadini; Sadollah Shamsadini
Volume 3, Issue 1 , March 2006, , Pages 30-34
Abstract
Background: Thalassemia patients are more susceptible to hepatitis than the normal population due to the frequent blood transfusions. Objective: To determine the immune response of children with major ß-thalassemia, by measuring anti-hepatitis B surface antibody (anti-HBs Ab) following the last ...
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Background: Thalassemia patients are more susceptible to hepatitis than the normal population due to the frequent blood transfusions. Objective: To determine the immune response of children with major ß-thalassemia, by measuring anti-hepatitis B surface antibody (anti-HBs Ab) following the last HBV vaccine injection. Methods: This study was carried out on 215 thalassemic children who received three standard intramuscular recombinant HBV vaccines. Children age ranged between 1-4.5 with a mean age of 3.37 years. Based on the time lapsed since last vaccine injection, the subjects were divided into three groups; 0-15 months, 15-30 months and 30-45 months, respectively. Based on the serum levels of anti-HBs antibody, subjects were categorized as: good responders (anti-HBs >100 IU/Lit), low responders (anti-HBs 10-100 IU/Lit) and non-responders (anti-HBs <10 IU/Lit). Results: The mean range of anti-HBs level in the above mentioned groups were 205.34, 128.8 and 54.25 IU/lit, respectively (P<0.0001). In girls, the mean antibody level was 104.2 and in boys it was 95.8 IU/Lit (P>0.05). Out of 215 selected individuals 75 (35%) were good responders, 65(30%) low responders and 75 (35%) non-responders. Conclusion: Standard HBV vaccination in thalassemic children results in an immune response in more than 65% of the subjects. Therefore, assessment of anti-HBs antibody level, 45 months after the last vaccination, is recommended.
Mohammad Motamedifar; Farhad Handijani; Nahal Hadi; Mohammad Kazem Shahkarami; Davoud Mehrabani
Volume 3, Issue 1 , March 2006, , Pages 43-46
Abstract
Background: Varicella–zoster virus (VZV) causes herpes zoster and varicella (Chicken-pox), usually a mild disease which is diagnosed clinically with few complications. However, in neonates and healthy adults it can have a severe presentation. Herpes zoster results from VZV reactivation later in ...
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Background: Varicella–zoster virus (VZV) causes herpes zoster and varicella (Chicken-pox), usually a mild disease which is diagnosed clinically with few complications. However, in neonates and healthy adults it can have a severe presentation. Herpes zoster results from VZV reactivation later in life. Objective: To determine the seroprevalence of VZV in elementary school children aged 6-10 years in Shiraz, Iran. Methods: A cross-sectional seroprevalence survey was conducted on 270 healthy subjects. All serum samples were investigated for immunoglobulin G (IgG) antibody against VZV using a commercial enzyme linked immunosorbent assay (ELISA). Results: Among the studied population, 175 (64.8%) had no detectable antibody levels. The overall seroprevalence rate was 35.2%. A breakdown of seropositivity to VZV according to age was as follows; 10 years old, 50%, 9 years old, 48.2%, 8 years old, 27.3%, 7 years old, 32.1%, and 6 years old, 13.2%. Conclusion: As VZV susceptibility in the studied age groups was higher than the expected rate, therefore childhood VZV vaccination is recommended in our region.