Anticardiolipin and anti-beta2GP1 antibodies were measured in 50 patients with HTLV-1-associated Myelopathy-Tropical Spastic Paraparesis (HAM-TSP) and the results were compared with those obtained for 34 HTLV-1-positive and 35 HTLV-1-negative controls, as well as 128 SLE patients. aCL but not anti-beta2GP1 was associated with HTLV-I infection. aCL was more prevalent than anti-beta2GP1 (32% vs. 8%) and was not associated with anti-beta2GP1 in HAM-TSP. IgA was the dominant isotype of aCL and anti-beta2GP1. The data suggest that tin HAM-TSP, IgA aCL are frequent and are associated with HTLV-1 infection.

محتوای آکاردئون

Amir Reza Tafreshian 1, Mehdi Etemadi 2, Reza Farid-Hosseini 3, Mansoor Salhi 4, Jalil

Tavakkol Afshari

Objective(s): HTLVI-1 is the first human retrovirus with limited endemic regions in the world. The
epidemiological studies have shown that the genetic background and immune response to the
virus have a significant role in HTLV-I-associated diseases. Among the genes are involved in
HTLV-I infection, the role of human leukocytes antigen (HLA) have been studied in different
population. In the present study we examined the association between HLA-DQB1 alleles and
HTLV-I infection in HAM/TSP patients, HTLV-I carriers and healthy controls in north east of Iran,
Mashhad.
Materials and Methods: The blood samples of 16 patients with HAM/TSP, 20 HTLV-1 carriers, and
30 healthy individuals were taken and DNA was extracted by salting out method. HLA-DQB1
typing was performed using PCR-SSP method and the frequency of HLA-DQB1 alleles were
compared by Fischer Exact Test.
Results: There was a significant difference between HAM/TSP patients and healthy controls in the
frequency of HLA-DQB1*07 (P=0.004, RR=7). Furthermore, we found that possession of HLADQB1*02 or HLA-DQB1*05 increased the risk of disease 1.5 times.
Conclusion: The data presented here suggest that both HLA-DQB1*07 and HLA-DQB1*06 are
associated with disease development.

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

Amir H. Sabouri, Saito M, Usuku K, Naghibzadeh Bajestan S, Mahmoudi M, Forughipour M, Sabouri Z, Abbaspour Z, Mohammad E. Goharjoo, Khayami E, Hasani A, Izumo Sh, Kimiyoshi Arimura, Farid R and Osame M.

Journal Gen Virol 2005;86:773–81

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disease observed only in 1–2% of infected individuals. HTLV-1 provirus load, certain HLA alleles and HTLV-1 tax subgroups are reported to be associated with different levels of risk for HAM/TSP in Kagoshima, Japan. Here, it was determined whether these risk factors were also valid for HTLV-1-infected individuals in Mashhad in northeastern Iran, another region of endemic HTLV-1 infection. In Iranian HTLV-1-infected individuals (n=132, 58 HAM/TSP patients and 74 seropositive asymptomatic carriers), although HLA-DRB1*0101 was associated with disease susceptibility in the absence of HLA-A*02 (P=0.038; odds ratio=2?71) as observed in Kagoshima, HLA-A*02 and HLA-Cw*08 had no effect on either the risk of developing HAM/TSP or HTLV-1 provirus load. All Iranian subjects possessed tax subgroup A sequences, and the protective effects of HLA-A*02 were observed only in Kagoshima subjects with tax subgroup B but not in those with tax subgroup A. Both the prevalence of HTLV-1 subgroups and the host genetic background may explain the different risks levels for HAM/TSP development in these two populations.

محتوای آکاردئون

محتوای آکاردئون

Farid R, Mehvar M, Baradaran H, Azimi N, SA Rezaee, Nikkhah P, Farid F

Med J Iran Hosp 2000;2(2):16-7

Seropositive rate of human T-cell leukemia virus type 1 (HTLV-1) in Mashhad (a city in the north east of Iran) is 2.3% which is a new endemic area in the world. Less than 2% of these HTLV-1 carriers suffer from HTL V-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Twenty serum samples from HAM/TSP patients, 44 from HTL V-I carriers and 20 from healthy individuals were tested for serum IL-2Rα by ELISA method. The mean soluble interleukin-2 receptor alpha (sIL-2Rα) in HAM/TSP patients, HTL V-I carriers and healthy subjects was 1420, 1460 and 374 pg/ml respectively. This study revealed that the level of sIL-2R in HAM/TSP patients and HTL V-I carriers was significantly more than healthy subjects (P<0.05), but no significant difference between HTLV-1 carriers and HAM/TSP patients was found.

Keyword: INTERLEUKIN-2Rα, HAM/TSP, HTLV-1

محتوای آکاردئون

Farid-Hosseini F, Pishnamaz R, Farid-Hosseini R, Abbaszadegan M, Mahmoodi M, Rasteen M

Arch Iran Med 2001;4(4):183-7

Background: Mashhad, a city in northern Iran, is a newly recognized endemic area for a retrovirus, the Human T-cell Lymphotropic Virus type I (HTLV-I). This virus is the causative agent of a chronic slowly progressive cord syndrome called HTLV-I associated with Human T-cell virus type I-associated myelopathy or/tropical spastic paraparesis (HAM/TSP) and has tropism for CD4+ T- cells, which results in T-cell activation that escape the autocrine pathway. The purpose of this study was to determine the immuno-phenotypic features of peripheral blood lymphocytes of HAM/TSP patients, especially differential expression ofinterleukin-2 receptor α (IL-2Rα) chain on the surface of the T-cells of HAM/TSP patients, HTLV-I carriers and healthy controls.

Material and Methods: Subjects in this case-control study included 20 HAM/TSP patients, 14 HTLV-I carriers and 12 healthy controls. The absolute white blood cell count and the differential cell count were determined by hematologic analysis and the relative and absolute number of peripheral blood CD3+ CD25+ T-cells were determined by flowcytometry.

Results: The relative number of lymphocytes (36±9%), relative number of CD3+ cells (74±7%) and the relative and absolute number of CD25/3+ cells (21±8%, 0.309±0.155 x109/1) were significantly higher in HAM/TSP patients than healthy controls (29±7%, 68±4%, 13±3%, 0.187±0.065 x109/1) (p<0.05). The relative lymphocyte (36±5%) and relative CD25/3+ (18±5%) cell counts were significantly higher in carriers in comparison with controls. No significant differences were present in these parameters between carriers and HAM/TSP patients.

Conclusion: This differential pattern of T-cell activation markers among the study groups may have striking diagnostic and therapeutic implications.

Keywords: HTLV-I, tropical spastic paraparesis, asymptomatic carrier, Interleukin 2-Rα chain

محتوای آکاردئون

محتوای آکاردئون

Rafatpanah H, Farid R, Golanbar G, and Jabbari Azad F

Iran J Allergy Asthma Immunol 2006;5(4): 153-66

Although the structure of human T lymphotropic virus type I (HTLV-I) has been known well, the function of some proteins encoded by HTLV-I PX region is not fully understood. Furthermore, the responses of the immune system to HTLV-I remain still unknown. Most of HTLV-I-infected individuals show a strong and persistently activated cytotoxic T-cell (CTL) response to the virus. The frequency of HTLV-I specific CTL is higher in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) compared with HTLV-I carriers. However, the efficacy of the immune response determines the outcome of HTLV-I-associated diseases. Among the risk factors which contribute to the observed differences between HAM/TSP patients and HTLV-I carriers, the interaction between different genes and/or environmental factors seem to be important. These factors may also involve in outcome of HTLV-I infection in infected individuals.

Keywords: CTL response, Cytokine gene polymorphism, HAM/TSP, HTLV-I, MHC

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

Kchour G, Tarhini M, Sharifi N, Farid R, Khooei AR, Shirdel A, Afshari JT, Sadeghian A, Otrock Z, Hermine O, El-Sabban M, Bazarbachi A

Leuk Lymphoma 2008;49(2):265-70

Adult T-cell leukemia-lymphoma (ATLL) is a rapidly progressive lymphoproliferative disorder secondary to infection with the human T cell lymphotropic virus type I (HTLV-I). The role of angiogenesis in the development and prognosis of many hematologic malignancies is established. We have previously shown that ATLL derived cells secrete high levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), induce endothelial tube formation in vitro and establish functional gap junction-mediated communication with endothelial cells. We also demonstrated that plasma from ATLL and tropical spastic paraparesis/HTLV-I associated myelopathy patients exhibit very high levels of VEGF and b-FGF. Recently, we showed that treatment with the combination of zidovudine and interferon alpha reduced both HTLV-I proviral load and importantly VEGF plasma levels suggesting a potential anti-angiogenic effect of this therapy. In this report, we evaluated microvessel density (MVD) in involved organs from 20 patients with ATLL, as compared to normal organs from matched controls. We show evidence of significantly increased MVD in all tested involved organs from ATLL patients, suggesting that angiogenesis plays an important role in the development or organ invasion of ATLL, and could represent a potentially interesting target for anti-angiogenic therapy of ATLL.

Danon, Yehuda

Final rept. 16 Oct 1991-9 Jun 1993

The report summarizes the two years of contract of the research aimed to define newly recognized high risk population for HTLV-I infection. To define the extent of HTLV-I infection among groups of Jewish immigrants to Israel with an increased frequency of Adult T-cell Leukemia (ATL). Various serological and molecular screening of methods were used, including ELISA and PCR use for molecular survey by amplification of HTLV-I proviral DNA from peripheral blood mononuclear cells DNA. overall rate of infection is 12% for Jews arriving from Khurusan-North-Eastern Iran. No positive HTLV-I carries were found from other parts of Iran, Ethiopia, and other Mid-Eastern countries, We could not identify HTLV-I seropositive patients in Insulin Dependent Diabetes Mellitus (IDDM) patients in children with non-Burkitt lymphomas, Psoriasis and Parapsoriasis patients, DNA Sequence data for HTLV-I isolates are provided showing similar sequence to African isolates. HTLV-I, Epidemiology, Polymerase, Virus, Aids, Biotechnology, RAD I.

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

Vidal AU, Gessain A, Yoshida M, Tekaia F, Garin B, Guillemain B, Schulz T, Farid R, De The G

J Gen Virol 1994;75: 3655-66

Proviral DNA was obtained from ex vivo peripheral blood mononuclear cells of 75 human T cell leukaemia/ lymphoma virus type I (HTLV-I)-infected individuals who were either asymptomatic or had adult T cell leukaemia or HTLV-I-associated myelopathy/ tropical spastic paraparesis. Amplified long terminal repeats (LTRs) were analysed for restriction fragment length polymorphisms (RFLPs). The results, together with previously published LTR data (a total of 180 specimens analysed), showed the presence of 12 different RFLP profiles with four major molecular subtypes. Furthermore, a fragment of 413 bp (nucleotides 22 to 434) of theU3/R region was sequenced for 12 new HTLV-I specimens originating from Central and West Africa (8cases), Iran (1 case), Caribbean (2 cases) and Reunion Island (1 case). Phylogenetic analysis using three different techniques (maximum parsimony, neighbor join ingand UPGMA) comparing these 12 strains (including four new African HTLV-I variants) with the 30 published partial HTLV-I LTR sequences (nt 120 to434) showed the existence of clusters of molecular variants in discrete geographical areas. The topology of the phylogenetic trees is thought to reflect HTLV-I evolution and the migrations of virally infected populations in the recent or distant past. Furthermore, there was a nearly perfect concordance between the clustering based on the LTR sequence homologies and the LTRRFLP subtypes suggesting that this rapid and simple technique is well suited to the investigation of HTLV-I molecular epidemiology. These results allow a new phylogenetic classification of HTLV-I genotypes into five major molecular subtypes: Cosmopolitan (C) subtype widespread all over the world, Japanese (J) subtype, West African (WA) subtype, Central African (CA)subtype and Melanesian (M) subtype.

Farid R, Shirdel A, Etemadi M, Rafatpanah H, Baradaran H, Farid F, Nikbin B

Arch Iran Med 1999;1(2): 24-5

Introduction: High prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) infection and disease has been identified in northeastern Iran. This study was conducted to determine the phylogenesis of the HTLV-1 in this highly prevalent area.

Materials and Methods: DNA in six patients was obtained from peripheral blood. Mononuclear cells from four patients with ATL and one with TSP/HAM and another asymptomatic HTLV-1 seropositive patient were studied. Amplified long ferminal repeats (LTRS) were analyzed for restriction fragment length polymorphisms. Phylogenetic analysis by PCR technique and primers LTR1 and LTR2 were used and compared with HTLV-1 from patients with other molecular strains.

Results: The results show that genotype classification of HTLV-1 is of cosmopolitan subtype.

Conclusion: The results suggest that the introduction of the HTLV-1 virus into the Northwest of Iran must have occurred over the past several centuries.

Keywords: HTLV-1 retrovirus Phylogeny Leukemia, T-Cell

Rafatpanah H, Pravica V, Farid R, Abbaszadegan MR, Tabatabaei A, Goharjoo A, Etemadi M, and Hutchinson I

Hum Immunol 2004;65(8):839-46

Human T lymphotropic virus I (HTLV-I) specific cytotoxic T lymphocytes (CTL) recognize the products of the HTLV-I Tax, in the context of HLA-A2 and kill their target through a perforin-dependent mechanism. The efficiency of the CTL response may lead HTLV-I infected individuals to remain carriers or to the development of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Perforin is a cytolytic molecule that contributes to CTL-mediated killing of virus-infected cells. Thus polymorphism in the perforin gene may determine the efficiency of the CTL response in HTLV-I infected individuals. In this study, we performed single-stranded conformational polymorphism (SSCP) and DNA sequencing to analyze the promoter, 5= UTR and first intron of the perforin gene to identify novel polymorphisms. We detected a novel polymorphism in the first intron at position _418*C/T, relative to the transcription start site. Genotyping of patients with HAM/TSP, HTLV-I carriers, and healthy controls revealed that the frequency of the C allele was statistically significantly increased in HAM/TSP patients compared with healthy controls group (p_0.005). The frequency of the C allele was higher, but not significantly so, in the HAM/TSP group compared with HTLV-I carriers (p=0.09), whereas there was no difference between HTLV-I carriers and healthy controls. Our results suggest that the perforin _418*C/T polymorphism is associated with the outcome of HTLV-I infection.

KEYWORDS: perforin; gene; polymorphism; HTLV-1; viral resistance.

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

محتوای آکاردئون

Kchour GH, Makhoul Nadine J, Mahmoudi M, Kooshyar MM, Shidel A, Rastin M, Rafatpanah H, Tarhini M, Zalloua Pierre A, Hermine O, Farid R, Bazarbachi A

Leuk Lymphoma 2007;48(2):330–6

Human T-cell lymphotropic virus type I (HTLV-I) associated adult T-cell leukemia/lymphoma (ATLL) is endemic in southern Japan, the Caribbean, intertropical Africa, and Brazil. Recently north east Iran, particularly the region of Mashhad, has been recognized as a new endemic region. ATLL is an aggressive T-cell lymphoproliferative disorder. Patients with ATLL have high plasma levels of VEGF that induce angiogenesis. Prognosis of ATLL remains poor because of immunosuppression and intrinsic resistance to chemotherapy. Important advances in the treatment of ATLL were reported with the combination of zidovudine (AZT) and interferon-a. We investigated the effect of AZT/IFN treatment on vascular endothelium growth factor (VEGF) plasma levels and HTLV-I proviral load in ATLL patients from the region of Mashhad.

We confirmed that AZT/IFN treatment induces a high response rate and prolonged survival with minimal side effects. We also confirmed that VEGF plasma levels and HTLV-I proviral load are higher in ATLL patients than in asymptomatic carriers. We finally showed that AZT/IFN treatment reduced both HTLV-I proviral load and importantly VEGF plasma levels, suggesting a potential antiangiogenic effect of this therapy. These results provide further evidence for the efficacy and the mechanism of action of AZT/IFN therapy for ATLL in a developing country.

Keywords: zidovudine, interferon, viral load, HTLV-I, ATLL