Publications by authors named "Sanaz Ahmadi Ghezeldasht"

16 Publications

  • Page 1 of 1

Evaluation of iron, ferritin, copper, and ceruloplasmin along with proviral load in human T lymphotropic virus type 1-associated myelopathy.

J Neurovirol 2021 Apr 20. Epub 2021 Apr 20.

Department of Neurology, Faculty of Medicine, Qaem Hospital, Mashhad University of Medical Sciences, Ahmadabad Avenue, 91766-99199, Mashhad, Iran.

Human T-cell lymphotropic virus type 1 (HTLV-1) infection can cause HTLV-I-associated myelopathy (HAM). In this study, we evaluated the levels of serum iron, ferritin, copper, and ceruloplasmin, and their correlations with HTLV-1 proviral load (PVL) and standard indices of HAM severity. In total, 114 subjects were recruited in this cross sectional study in Qaem Hospital, Mashhad, Iran between 2017 and 2018, including 36 HAM and 32 asymptomatic cases (ACs) and 46 healthy people (HSs). The clinical examination and evaluation of serum levels of biochemical factors and proviral load were performed. The PVL in HAM and ACs were 1835.49 ± 382.81 and 280.97 ± 67.41 copies/10 PBMCs, which statistically differed. Significant differences were also observed in plasma levels of iron, copper, and ceruloplasmin, among the three groups, while ferritin level was not considerably different. For HAM severity, the mean Osame motor disability scale (OMDS) and overactive bladder-validated-8-questionnaire (OABV-8) scores were 4.97 ± 0.38 and 15.75 ± 0.83, respectively, that had no significant correlations with the biochemical variables. Even though the studied elements in HAM group did not affect the severity of the disease, the levels of copper and ceruloplasmin might be determinants of the development and progression of HAM, as they are shown to play role in progression of other neurological diseases.
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http://dx.doi.org/10.1007/s13365-021-00961-5DOI Listing
April 2021

HTLV-1 oncovirus-host interactions: From entry to the manifestation of associated diseases.

Rev Med Virol 2021 Mar 19. Epub 2021 Mar 19.

Inflammation and Inflammatory Diseases Division, Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Human T lymphotropic virus type-1 (HTLV-1) is a well-known human oncovirus, associated with two life-threatening diseases, adult T cell leukaemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The study of this oncogenic virus is significant from two different aspects. First, HTLV-1 can be considered as a neglected public health problem, which may spread slowly worldwide. Second, the incidence of HTLV-1 associated diseases due to oncogenic effects and deterioration of the immune system towards autoimmune diseases are not fully understood. Furthermore, knowledge about viral routes of transmission is important for considering potential interventions, treatments or vaccines in endemic regions. In this review, novel characteristics of HTLV-1, such as the unusual infectivity of virions through the virological synapse, are discussed in the context of the HTLV-1 associated diseases (ATL and HAM/TSP).
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http://dx.doi.org/10.1002/rmv.2235DOI Listing
March 2021

Occult hepatitis C virus infection in the Middle East and Eastern Mediterranean countries: A systematic review and meta-analysis.

World J Hepatol 2021 Feb;13(2):242-260

Blood Borne Infections Research Center, Academic Center for Education, Culture and Research (ACECR), Razavi Khorasan Branch, Mashhad 91779-49367, Iran.

Background: The presence of hepatitis C virus (HCV) RNA in liver tissue or peripheral blood mononuclear cells with no identified virus genome in the serum has been reported worldwide among patients with either normal or elevated serum liver enzymes. The characterization of occult HCV infection (OCI) epidemiology in the Middle East and Eastern Mediterranean (M and E) countries, a region with the highest incidence and prevalence rates of HCV infection in the world, would be effective for more appropriate control of the infection.

Aim: To estimate the pooled prevalence of OCI in M and E countries using a systematic review and meta-analysis.

Methods: A systematic literature search was performed using international, regional and local electronic databases. Some conference proceedings and references from bibliographies were also reviewed manually. The search was carried out during May and June 2020. Original observational surveys were considered if they assessed the prevalence of OCI among the population of M and E countries by examination of HCV nucleic acid in peripheral blood mononuclear cells in at least 30 cases selected by random or non-random sampling methods. The meta-analysis was performed using Comprehensive Meta-analysis software based on heterogeneity assessed by Cochran's test and -square statistics. Data were considered statistically significant at a value < 0.05.

Results: A total of 116 non-duplicated citations were found in electronic sources and grey literature. A total of 51 non-overlapping original surveys were appraised, of which 37 met the inclusion criteria and were included in the analysis. Data were available from 5 of 26 countries including Egypt, Iran, Pakistan, Saudi Arabia, and Turkey. The overall prevalence rate of OCI was estimated at 10.04% (95%CI: 7.66%-13.05%). The lowest OCI rate was observed among healthy subjects (4.79%, 95%CI: 2.86%-7.93%). The higher rates were estimated for patients suffering from chronic liver diseases (12.04%, 95%CI: 5.87%-23.10%), and multi-transfused patients (8.71%, 95%CI: 6.05%-12.39%). Subgroup analysis indicated that the OCI rates were probably not associated with the studied subpopulations, country, year of study, the detection method of HCV RNA, sample size, patients' HCV serostatus, and sex (all > 0.05). Meta-regression analyses showed no significant time trends in OCI rates among different groups.

Conclusion: This review estimated high rates of OCI prevalence in M and E countries, especially among multi-transfused patients as well as patients with chronic liver diseases.
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http://dx.doi.org/10.4254/wjh.v13.i2.242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934012PMC
February 2021

Prevalence, genotypes and phylogenetic analysis of human papillomaviruses (HPV) in northeast Iran.

Int J Infect Dis 2021 Feb 10;103:480-488. Epub 2020 Dec 10.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Objectives: Human papillomaviruses (HPV) are the main etiology of invasive cervical cancer. Together HPV and viral hepatitis account for the cause of 25% of cancers in developing countries. To evaluate the association between population movements and the spread of HPV, this study looked at prevalence, genotypes, and phylogenetic assessment of HPV in Great Khorasan, a pilgrimage-tourism province in northeast Iran.

Methods: From March 2013 to July 2018, 567 samples were collected from three groups in Khorasan: Razavi and North Khorasan provinces (highly mobile population); South Khorasan province (conservative and desert); and diverse group (tourists).

Results: HPV prevalence was 48.4% in Razavi and North Khorasan (first group); 19.9% in South Khorasan (second group); and 33.6% in the diverse group. The four most common HPV genotypes were HPV-6, 11, 51 and 16, in the first group; HPV-6, 11, 16 and 58 in the second group; and HPV-6, 11, 16 and 53/89 in the diverse group. The most frequent genotypes that are known as high risk for cervical cancer were HPV-51 in the first group, HPV-16 in the second group and the diverse group. Among low-risk genotypes, HPV-6, and HPV-11 were more frequent in all groups. DNA sequencing and phylogenetic analysis of 20 HPV-positive samples showed that the distributions of the HPV genotypes were HPV-6 (50%), 11 (10%), 67 (5%), 16 (15%), 31 (10%), 54 (5%), and 89 (5%).

Conclusions: The findings show that areas associated with population movement should be frequently monitored for infectious diseases, while conservative and less populated areas have less risk for virus spread and endemicity. Health authorities should focus more on the establishment of HPV diagnostic facilities, screening, vaccination, and enhancement of public knowledge in these regions.
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http://dx.doi.org/10.1016/j.ijid.2020.12.015DOI Listing
February 2021

Prevalence and Associated Risk Factors of HTLV-1 and Co-infections of Blood-Borne Viruses in Birjand, Iran's Eastern Border.

Arch Iran Med 2020 10 1;23(10):672-677. Epub 2020 Oct 1.

Birjand Infectious Disease Research Center, Birjand University of Medical Sciences, Birjand, Iran.

Background: Blood-borne viruses (BBVs) are one of the most important public health concerns. South Khorasan has a long border with Afghanistan and concern has risen there about blood-borne oncogenic viral infections. The aim of the present study was to evaluate the prevalence and associated risk factors of human T-lymphotropic virus 1 (HTLV-1) and co-infections of BBVs in Birjand, Iran's eastern border.

Methods: In this cross-sectional study, 3441 subjects were tested for sero-prevalence of HTLV-1 by ELISA. The data on demographic features, HTLV-1-related risk factors and other characteristics of the population were analyzed by Pearson chi-square and logistic regression tests. Finally, the co-infection of BBVs was evaluated in the study.

Results: The prevalence of HTLV-1 was 0.3% (95% CI: 0.12-0.48). Notably, the sero-prevalence of HIV, hepatitis B virus (HBV), hepatitis D virus (HDV), and hepatitis C virus (HCV) in our previous studies was reported at 0%, 0.2%, 1.2% and 1.6%, respectively. The results indicated that the occurrence of HTLV-1 infection was associated only with the history of hospitalization (odds ratio [OR]: 0.27, 95% CI: 0.07-0.97, with P = 0.04). The co-infection of HBV with HCV was the most common (2.35%), while a co-infection rate of 1.17% was found for both HBV/HTLV-1 and HBV/HDV.

Conclusion: Although a higher prevalence of the viruses was expected, it was close to the overall Iranian population. With respect to close relationship with an HTLV-1 endemic area (Mashhad and Neyshabour), the prevalence is very low; however, more attention is needed. Our findings reinforce the importance of increasing knowledge about BBV-related health risk behaviors to prevent the emergence of new cases, especially in low-risk populations.
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http://dx.doi.org/10.34172/aim.2020.85DOI Listing
October 2020

The IL-18, IL-12, and IFN-γ expression in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, HTLV-1 carriers, and healthy subjects.

J Neurovirol 2020 06 8;26(3):338-346. Epub 2020 Apr 8.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Faculty of Medicine, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad, 9177948564, Iran.

Interleukin (IL)-12, IL-18, and interferon gamma (IFN-γ) can induce Th1-inflammatory responses in favor of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) manifestation. In this study, the gene expression and plasma levels of these cytokines were evaluated. The peripheral blood mononuclear cells (PBMCs) in 20 HAM/TSP patients, 21 asymptomatic carriers (ACs), and 21 healthy subjects (HSs) were assessed for the expression of IL-18, IL-12, and IFN-γ, using qRT-PCR. The plasma level of IL-18 and IFN-γ were measured by an ELISA method. The mean of HTLV-1 proviral load (PVL) in the HAM/TSPs was 1846.59 ± 273.25 and higher than ACs at 719.58 ± 150.72 (p = 0.001). The IL-12 was considerably expressed only in nine ACs, five HAM/TSPs, and all HSs. Furthermore, the gene expression and plasma levels of IL-18 were lower in the HTLV-1-positive group than the control group (p = 0.001 and 0.012, respectively); however, there was no significant difference between the ACs and HAM/TSPs. The IFN-γ level was higher in the HTLV-1-positive group (p < 0.001) than HSs. Although there were no correlation between plasma levels of IL-18 and IFN-γ with PVL in the ACs, a positive correlation was observed between plasma IL-18 levels and PVL (r = 0.654, p = 0.002). The highest levels of IFN-γ were observed in the HAM/TSPs which has a significant correlation with HTLV-1-HBZ (r = 0.387, p = 0.05) but not with Tax. However, no significant correlation was found between PVL and proinflammatory pattern. Apart from the IFN-γ as a lymphokine, as a host factor, and HTLV-1-HBZ, as a viral agent, the other proinflammatory monokines or HTLV-1 factors are among the less-effective agents in the maintenance of HAM/TSP.
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http://dx.doi.org/10.1007/s13365-020-00832-5DOI Listing
June 2020

Abnormal vitamin D and lipid profile in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

Mol Biol Rep 2020 Jan 11;47(1):631-637. Epub 2019 Nov 11.

Inflammation and Inflammatory Diseases Division, Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

The HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease of host-HTLV-1 interactions. In many virus-associated diseases and multiple sclerosis, the importance of vitamin-D and lipid profile has been demonstrated, thus similarly, their impacts were evaluated in HAM/TSP patients, in this study. Vitamin D and lipid profile were assessed in 120 healthy subjects (HSs), along with a proviral load (PVL) in 91 HAM/TSPs and 169 HTLV-1 carriers (ACs). The mean level of triglyceride and LDL in the HAM/TSPs were higher than HSs (P = 0.008 and 0.008, respectively), but no significant difference has been found between ACs and HSs. However, the level of HDL and vitamin-D in the HAM/TSP subjects were lower than HSs (P = 0.01 and P = 0.006, respectively). In HTLV-1 infected subjects, PVL was statistically associated with cholesterol (R = 0.24, P = 0.038), triglycerides (R = 0.26, P = 0.01) and HDL (R = 0.28, P = 0.001), and in HAM/TSPs there was a strong association between the severity of the disease, as determined by the OMDS and cholesterol (P = 0.01). Furthermore, in the HAM/TSPs, positive correlations between vitamin-D and age (R = 0.23, P = 0.028) and triglycerides (R = 0.38, P = 0.001) were found, also a significant correlation between PVL and LDL (R = 0.21, P = 0.001) and a weak correlation between PVL and OMDS (R = 0.4, P = 0.07) were noted. However, there was no correlation between PVL and urinary disturbance. Furthermore, PVL range of more than 600 copies/10 lymphocytes had a strong correlation with OMDS (P = 0.05), but not with urinary disturbance. It's more likely that HAM/TSP patients have an imbalanced lipid profile and low levels of vitamin D and may represent a potentially useful target for intervention in HTLV-1 associated diseases.
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http://dx.doi.org/10.1007/s11033-019-05171-1DOI Listing
January 2020

Prediction of HCV load using genotype, liver biomarkers, and clinical symptoms by a mathematical model in patients with HCV infection.

Microbiol Immunol 2019 Nov 26;63(11):449-457. Epub 2019 Aug 26.

Department of Mycology and Parasitology, Mashhad University of Medical Sciences, Azadi-Squre, Medical Campus, Mashhad, 9177948564, Iran.

Hepatitis C virus (HCV) infection is a major public health problem with about 1.75 million new HCV cases and 71 million chronic HCV infections worldwide. The study aimed to evaluate clinical, serological, molecular, and liver markers to develop a mathematical predictive model for the quantification of the HCV viral load in chronic HCV infected patients. In this cross-sectional study, blood samples were taken from 249 recently diagnosed HCV-infected subjects and were tested for liver condition, viral genotype, and HCV RNA load. Receiver operating characteristics (ROC) curves and multiple linear regression analysis were used to predict the HCV-RNA load. Genotype 3 followed by genotype 1 were the most prevalent genotypes in Mashhad, Northeastern Iran. The maximum levels of viral load were detected in the mixed genotype group, and the lowest levels in the undetectable genotype group. The log of the HCV viral load was significantly associated with thrombocytopenia and higher serum levels of alanine transaminase (ALT). In addition, the log HCV RNA was significantly higher in patients with arthralgia, fatigue, fever, vomiting, or dizziness. Moreover, genotype 3 was significantly associated with icterus. A ROC curve analysis revealed that the best cut-off points for serum levels of aspartate aminotransferase (AST), ALT, and alkaline phosphatase (ALP) were >31, >34, and ≤246 IU/L, respectively. Sensitivity, specificity, and positive predictive values for AST were 87.7%, 84.36%, and 44.6%, for ALT they were 83.51%, 81.11%, and 36%, and for ALP were 72.06%, 42.81%, and 8.3%, respectively. A mathematical regression model was developed that could estimate the HCV-RNA load. Regression model: log viral load = 7.69 - 1.01 × G3 - 0.7 × G1 + 0.002 × ALT - 0.86 × fatigue.
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http://dx.doi.org/10.1111/1348-0421.12735DOI Listing
November 2019

HTLV-1-host interactions facilitate the manifestations of cardiovascular disease.

Microb Pathog 2019 Sep 6;134:103578. Epub 2019 Jun 6.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Atherosclerosis is a multifactorial life-threatening disease which an epidemiologic study in Northeastern Iran showed its association with HTLV-1 infection. Therefore, a cross-sectional study of 39 newly diagnosed subjects with angiography test in three groups including 14 coronary artery diseaseHTLV-1 (CADHTLV-1), 8 CADHTLV-1, and 17 CADHTLV-1 patients and 11 healthy subjects (CADHTLV-1) were conducted. In the present study, Tax and proviral load (PVL) as HTLV-1 virulence factors, along with host chemokine receptor 1 (CCR1), and CCR2 were investigated. Real-time PCR TaqMan method was carried out for PVL measurement and HTLV-1-Tax, CCR1, and CCR2 expressions in peripheral blood mononuclear cells (PBMCs). Furthermore, the main risk factors, lipid profile, and complete blood count (CBC) were assessed. Expression of CCR1 in CADHTLV-1 group was higher than CADHTLV-1 (P = 0.01) and healthy subjects (P = 0.02). Expression of CCR1 in CADHTLV-1 was higher in comparison with CADHTLV-1group but did not meet 95% CI (P = 0.02), but meaningful at 91% CI. In addition, expression of CCR2 in CADHTLV-1 subjects was higher than CADHTLV-1 and CADHTLV-1 (P = 0.001, P = 0.005, respectively). In CADHTLV-1 subjects, CCR2 was higher than CADHTLV-1 (P = 0.03). The mean PVL in CADHTLV-1 group is more than CADHTLV-1 (P = 0.041). In HTLV-1 patients Tax had a positive correlation with cholesterol (R = 0.59, P = 0.01), LDL (R = 0.79, P = 0.004) and a negative correlation with HDL (R = -0.47, P = 0.04). These correlations were stronger in CADHTLV-1. Findings showed that HTLV-1 could alter the expression of CCR2 and, less effect, on CCR1. Moreover, the strong correlation between CCR2 and HTLV-1-Tax with cholesterol, LDL and HDL showed that Tax as the main HTLV-1 virulence factor in cytokine deregulation might be had indirect effects on cholesterol, LDL, and HDL levels.
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http://dx.doi.org/10.1016/j.micpath.2019.103578DOI Listing
September 2019

Distribution of Hepatitis C Virus Genotypes in Patients with Major β-Thalassemia in Mashhad, Northeast Iran.

Middle East J Dig Dis 2018 Jan 7;10(1):35-39. Epub 2018 Jan 7.

Blood Borne Infections Research Center, Academic Center for Education, Culture, and Research (ACECR), Razavi Khorasan Branch, Mashhad, Iran.

BACKGROUND Hepatitis C virus (HCV) is considered to be the major cause of post-transfusion hepatitis in patients with thalassemia. We aimed to determine the HCV prevalence, genotypes, and viral load among patients with major β-thalassemia in Mashhad, Iran. METHODS Medical records of all 550 patients with major β-thalassemia who referred to ThalassemiaHemophilia Center of Mashhad (Sarvar Clinic) were reviewed from October to November 2011. Plasma samples of the patients were tested for the presence of anti-HCV antibodies by enzyme linked immunosorbent assay. Real-time polymerase chain reaction (PCR) was used to determine viral genotype and HCV RNA titer. RESULTS HCV antibodies were detected in 37 individuals (6.73%) including 17 men and 20 women with mean age of 25.2 ± 8.4 years. The PCR analysis was performed for 27 patients, of whom HCV RNA was detected in 17 patients (63.0%). Viral titers were investigated in 14 subjects and a high viral load more than 600000 copies/mL was observed in 6 patients (42.9%). The most prevalent genotypes were 3a (50.0%) followed by 1a (37.5%). No significant correlation was found between genotype and age, sex, serum ferritin, liver tests, and HCV RNA titer. CONCLUSION HCV infection among patients with thalassemia is more common than general population in Mashhad, northeast Iran. The dominant HCV subtype is 3a followed by 1a. These findings could help health authorities to provide preventive measures, and practitioners to choose the right protocol of treatment for the patients.
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http://dx.doi.org/10.15171/mejdd.2017.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903925PMC
January 2018

Prevalence of Hepatitis C Virus Infection in General Population of Mashhad, Northeastern Iran.

Iran J Public Health 2017 Mar;46(3):408-413

Immunology Research Center, Inflammation and inflammatory Diseases Division, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Hepatitis C Virus (HCV) infection is one of the major blood-borne infections worldwide. HCV carriers may develop chronic hepatitis leading to liver cirrhosis and hepatocellular carcinoma (HCC). There is no overall estimate of the infection prevalence in the northeast of Iran. We have performed this research in order to determine accurately the prevalence and risk factors of HCV infection among general population in Mashhad.

Methods: During 2009, 1678 people between 1 to 90 yr old with the mean age of 29.1±18.5 yr were selected randomly by multistage sampling from different geographical regions of the city proportionate to sex and age distribution of population in 2006 census. ELISA was used to screen for antibodies and RT-PCR tested the positive samples.

Results: HCV infection was detected in 7/1654 cases; overall prevalence of the infection was 0.42% (95%CI: 0.17-0.87%), 0.80% and 0.11% among males and females, respectively (= 0.051). One HCV-infected subject was also positive for hepatitis B surface antigen (HBsAg), however, no cases showed HIV or HTLV seropositivity.

Conclusion: In comparison with similar studies, the prevalence of HCV infection in Mashhad is low.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395537PMC
March 2017

Rate of positive autoimmune markers in Human T lymphotropic virus type 1 carriers: a case-control study from Iran.

Int J Rheum Dis 2018 Jan 5;21(1):108-113. Epub 2017 Mar 5.

Rheumatic Diseases Research Centre, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Aim: Human T lymphotropic virus type 1 (HTLV-1) infection with high prevalence in the north-east of Iran, particularly in Mashhad, can lead to adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a variety of autoimmune diseases. The aim of the study was to examine the presence of autoimmune markers in HTLV carries.

Methods: Serum samples were obtained from blood donors in Mashhad, northeastern Iran. One hundred and five HTLV-1 positive (cases) and 104 age- and sex-matched HTLV-1 negative donors (controls) were assessed for presence of serum autoimmune markers by enzyme-linked immunosorbent assay.

Results: The mean ages of cases and controls were 40.8 ± 9.4 and 41.5 ± 9.3 years, respectively (P = 0.5). In the case group, 81.9% and in the control group 83.7% were male (P = 0.74). The frequency of positive antinuclear antibodies and anticyclic citrullinated peptide antibodies in the serum of the two groups were not significantly different (P = 0.68 and P = 0.62, respectively). Only one antineutrophil cytoplasmic antibody-positive case (1%) was observed in the group and no anti-phospholipid immunoglobulin G positivity was observed. The frequency of rheumatoid factor (RF) was greater in case group than in the control group, although the difference was not significant (P = 0.08). The amount of RF in all 12 RF positive sera were higher than normal levels (33-37 IU/mL).

Conclusion: Because we failed to detect any significant relation between serum autoimmune markers and HTLV-1 infection, and because of the relatively low prevalence of autoimmune diseases, it could be concluded that healthy HTLV-1 carriers do not produce rheumatologic-related auto-antibodies more than the healthy population.
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http://dx.doi.org/10.1111/1756-185X.13002DOI Listing
January 2018

Evaluation of T Regulatory Lymphocytes Transcription Factors in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Patients.

Appl Biochem Biotechnol 2017 Aug 18;182(4):1403-1414. Epub 2017 Jan 18.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an aggressive neurological disease. The CD4CD25 T cell population plays pivotal roles in the maintenance of immunological tolerance and prevention of such autoimmune diseases. In the current study, proviral load (PVL), factor forkhead box p3 (Foxp3), and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) gene expression and regulatory T cells (Tregs) counts of 21 HAM/TSP patients and 16 HTLV-1 healthy carriers (ACs) were measured using real-time PCR, TaqMan method, and flow cytometry. The demographic, history of disease, and severity of myelopathy were assessed by a checklist and the Osame motor disability score (OMDS). The mean OMDS for HAM/TSP was 4.82 ± 2.37 which had no significant correlation with Treg count or the expression of Foxp3, GITR, and PVL. The CD4CD25 cell counts had no significant differences between HAM/TSP and ACs. Findings revealed a higher PVL in HAM/TSPs (313.36 copies/10) compared to ACs (144.93 copies/10, p = 0.035). The Foxp3 and GITR mRNA levels were lower in HAM/TSP patients (11.78 and 13.80, respectively) than those in healthy carriers (18.44 and 21.00, p = 0.041 and 0.03, respectively). There was a significant correlation between Treg frequency and Foxp3 gene expression (R = 0.67, p = 0.006) and GITR and Foxp3 (R = 0.84, p = 0.042) in HAM/TSP patients. Furthermore, the transcription factors have strong correlations with CD4CD25 T cell frequencies. These findings suggest that HTLV-1 infection can modify the expression of main functional transcription factors, FOXP3 and GITR, which may lead to immune response deterioration of Tregs and consequently HAM/TSP manifestation.
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http://dx.doi.org/10.1007/s12010-017-2406-7DOI Listing
August 2017

Oncogenic Virus Infections in the General Population and End-stage Renal Disease Patients With Special Emphasis on Kaposi's Sarcoma Associated Herpes Virus (KSHV) in Northeast of Iran.

Jundishapur J Microbiol 2015 Mar 21;8(3):e14920. Epub 2015 Mar 21.

Research Center for HIV/AIDS, HTLV and Viral Hepatitis, Iranian Academic Center for Education, Culture and Research (ACECR), Mashhad Branch, Mashhad, IR Iran ; Inflammation and Inflammatory Diseases Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, IR Iran.

Background: Globally, almost 20% of cancers are related to infectious agents that can be prevented. Oncogenicity refers to viruses that may cause cancers, more importantly in immunocompromised subjects such as transplant and hemodialysis patients. Therefore, epidemiological studies are the first line for understanding the importance of these agents in public health, particularly, in mobile populations, tourism and pilgrimage regions.

Objectives: Oncogenic viral infections, such as hepatitis B virus (HBV), hepatitis C virus (HCV) and Epstein-barr virus (EBV) are the most common viral agents in immunocompromised patients. Furthermore, human T lymphocyte virus type I (HTLV-I), due to endemicity in Khorasan Razavi province located northeast of Iran as a pilgrimage region, and Kaposi's sarcoma associated herpes virus (KSHV), as an oncogenic herpesvirus in immunocompromised subjects have been investigated among the general population and those with end-stage renal diseases (ESRD).

Patients And Methods: A cross-sectional study was carried out among 1227 randomly selected individuals; 25 donors and 195 patients with ESRD, including 60 kidney transplant recipients and 135 dialysis patients from the Khorasan Razavi province, Iran. Serological tests were carried out using commercial enzyme-immunoassay kits. To confirm positive serology tests, the extracted viral DNA or RNA was examined for the presence of KSHV, HTLV-I and HCV by conventional PCR.

Results: The prevalence of KSHV infection in the general population was 1.71% (21/1227); 2.60% (10/384) males and 1.30% (11/843) females. In kidney transplants, viral infections occurred in 23.3% of subjects; including EBV, HTLV-I and HBV-HCV co-infection in 8.3%, 3.3% and 1.7%, respectively. In patients on hemodialysis, viral infections were present in 29.6% including EBV, HTLV-I and HBV-HCV co-infection in 2.2%, 5.9% and 16.3%, respectively. Seroprevalence of KSHV in patients with kidney transplants was 1.7% and in patients on dialysis was 3.0%. Furthermore, KSHV and HTLV-I genome was detected in 25% and 100% of seropositive subjects, respectively.

Conclusions: In conclusion, this study demonstrated that these tumor virus infections including HTLV-I, KSHV and particularly hepatitis viruses (HBV plus HCV) are prevalent in the general population and in patients on hemodialysis, which might be an important health concern in this region due to the mobile population.
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http://dx.doi.org/10.5812/jjm.14920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377171PMC
March 2015

Human T Lymphotropic Virus Type I (HTLV-I) Oncogenesis: Molecular Aspects of Virus and Host Interactions in Pathogenesis of Adult T cell Leukemia/Lymphoma (ATL).

Iran J Basic Med Sci 2013 Mar;16(3):179-95

Immunology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran.

The study of tumor viruses paves the way for understanding the mechanisms of virus pathogenesis, including those involved in establishing infection and dissemination in the host tumor affecting immune-compromised patients. The processes ranging from viral infection to progressing malignancy are slow and usually insufficient for establishment of transformed cells that develop cancer in only a minority of infected subjects. Therefore, viral infection is usually not the only cause of cancer, and further environmental and host factors, may be implicated. HTLV-I, in particular, is considered as an oncovirus cause of lymphoproliferative disease such as adult T cell leukemia/lymphoma (ATL) and disturbs the immune responses which results in HTLV-I associated meylopathy/tropical spastic parapresis (HAM/TSP). HTLV-I infection causes ATL in a small proportion of infected subjects (2-5%) following a prolonged incubation period (15-30 years) despite a strong adaptive immune response against the virus. Overall, these conditions offer a prospect to study the molecular basis of tumorgenicity in mammalian cells. In this review, the oncogencity of HTLV-I is being considered as an oncovirus in context of ATL.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881257PMC
March 2013

Population Movement and Virus Spreading: HEV Spreading in a Pilgrimage City, Mashhad in Northeast Iran; an Example.

Hepat Mon 2013 4;13(8):e10255. Epub 2013 Aug 4.

Research Center for HIV/AIDS, HTLV and Viral Hepatitis, Iranian Academic Center for Education, Culture and Research (ACECR), Mashhad, IR Iran.

Background: Hepatitis E Virus (HEV) infection is a significant public health concern and responsible for large outbreaks of acute hepatitis in poor sanitary and living conditions.

Objectives: To investigate the impact of population movements on virus spreading, a large-scale population-based survey was performed in a pilgrimage- tourism area, the great Mashhad, capital city of Khorasan province.

Patients And Methods: A cross-sectional study was carried out among 1582 randomly selected individuals from general population of Mashhad, north east of Iran, between May to September 2009. Serum samples were tested for total anti-HEV antibody using a specific enzyme linked immunoassay (ELISA) kit.

Results: The prevalence of HEV infection was 14.2% (225/1582) with a maximum of 25.5 % (14/55) in densely populated areas. The highest prevalence was observed in visitant areas (≥ 20%) near the holly shrine with crowded hotels and inns. The differences between these areas and other districts were statistically significant (P < 0.001). The findings indicated that 13.2% (95/718) of males and 15.0% (130/864) of females were HEV positive; this difference is not significant. Seroprevalence increases with age rising , from 12.8% in subjects less than five years to 28.6% in individuals with more than 65 years old. Although, there were no meaningful differences between HEV seropositivity and socio-economic status, Illiterate individuals were significantly at higher risk for infection than educated persons (P < 0.001).

Conclusions: These findings demonstrated that, high prevalence of HEV is related to populated district, which can reach to the highest rate in hotels and inns close to visitants. Traditional sanitation and water supplying systems are the second important factor for the virus transmission. Therefore, it can be concluded that such areas need efficient surveillance systems to prevent the spreading of infectious diseases.
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http://dx.doi.org/10.5812/hepatmon.10255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810681PMC
October 2013
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