Low prevalence of human T cell lymphotropic virus type 1 infection in patients with gastric cancer

BACKGROUND AND AIM: There have been few studies on the association between human T cell lymphotropic virus type 1 (HTLV-1) infection and cancer risk. It is still controversial whether or not HTLV-1 infection affects the incidence of several cancers. With this background, we aimed to evaluate the relationship between HTLV-1 infection and the occurrence of several types of cancers. METHODS: Subjects were 699 patients with cancer aged 50 years and older diagnosed between 1991 and 2004 at the Department of Medicine and Therapeutics, Ryukyu University Hospital, Okinawa, Japan, and 1365 control patients without cancer. The association between HTLV-1 infection and cancer (biliary tract, pancreatic, esophageal, gastric, colorectal, liver, and lung cancers) was analyzed by logistic regression analysis adjusted for age and sex. RESULTS: The infection rate of HTLV-1 in patients with gastric cancer was significantly lower than in controls (P = 0.01, adjusted odds ratio 0.46). The infection rate of HTLV-1 was not associated with increased or decreased risk of cancers other than gastric cancer. CONCLUSION: Our study indicated that the prevalence of HTLV-1 infection in patients with gastric cancer appears to be significantly lower than that in control patients.     

Molecular epidemiology of human T lymphotropic virus type 1 transmission in Okinawa,Japan

To clarify the route of human T lymphotropic virus type 1 (HTLV-1) transmission, we sequenced three proviral genome regions (gag, env, int) of HTLV-1 from 18 carriers in 7 families in Okinawa, Japan and compared the strains with isolates from other countries. The nucleotide substitution frequency among sequences derived from a single carrier was low; 0-0.24% in gag, 0-0.54% in env, and 0-0.34% in int. All sequences showed the closest identity to the Cosmopolitan strain, with differences of only 0-1.91%. All 8 mother/child pairs had identical nucleotide sequences. Of 3 pairs of spouses, 2 had identical sequences, with transmission probably from husband to wife. The mothers of both wives were HTLV-1-negative. The HTLV-1 sequence of the other wife showed three nucleotide differences from the sequence of her husband, but was identical to the sequence of her mother. These results support previous seroepidemiological studies that HTLV-1 transmission occurs from mother to children and also between spouses.     

Higher prevalence of fibromyalgia in patients infected with human T cell lymphotropic virus type I

OBJECTIVE:. Inflammatory rheumatic conditions including rheumatoid arthritis and Sj?gren's syndrome have been reported in individuals infected with human T cell lymphotropic virus type I (HTLV-I). Other chronic lymphotropic virus infections such as hepatitis C and human immunodeficiency virus are associated with fibromyalgia (FM). There are no reports about the association between HTLV-I infection and FM. We evaluated the association between FM and HTLV-I infection. METHODS: We conducted a case-control study with prevalent cases. Ex-blood donation candidates with HTLV-I infection from a blood bank cohort, and healthy blood donors as a control group, were submitted to rheumatologic evaluation to compare the prevalence of FM. The following covariables were also evaluated: other rheumatic diseases, age, sex, personal income, level of education, and depression. RESULTS: One hundred individuals with HTLV-I infection and 62 non-infected blood donors were studied. Thirty-eight (38%) HTLV-I infected individuals and 3 (4.8%) individuals from the control group presented the diagnosis of FM (OR 12.05, 95% CI 3.53-41.17). Other rheumatic diseases were also more prevalent in the infected group (37% vs 12.9%; OR 3.80, 95% CI 1.63-8.86). In multivariate analysis adjusted by the covariables, the association between HTLV-I and FM was statistically significant (OR 9.14, 95% CI 2.42-34.52). CONCLUSION: Our study shows a greater prevalence of FM in HTLV-I infected individuals, suggesting that FM may be associated with this viral infection.     

Study of autoantibodies in patients with keratoconjunctivitis sicca infected by the human T cell lymphotropic virus type 1

Human T cell lymphotropic virus type 1 (HTLV-1) is endemic in many regions of the world, including Brazil, and has been associated to several immunological manifestations such as arthritis, uveitis, dermatitis and Sjögren’s syndrome. This study was intended to evaluate the frequency of autoantibodies in patients infected with HTLV-1 and manifesting keratoconjunctivitis sicca (KCS). HTLV-1 patients with KCS, enrolled in a reference ambulatory of the city of Salvador, were tested for autoantibodies such as antinuclear antibodies, rheumatoid factor, anti-SSA/Ro and anti-SSB/La. Two comparison groups were also included: (a) HTLV-1 patients without KCS and (b) seronegative patients with KCS. Correlation of proviral load (PVL) in HTLV-1 patients with presence or absence of KCS was also assessed. No autoantibodies were detected in HTLV-1 patients with KCS. The PVL of HTLV-1 patients was higher in patients with KCS without other clinical manifestations customarily associated to HTLV-1. In conclusion, in this study, no changes were observed in humoral immunity concerning production of certain autoantibodies in HTLV-1-infected patients with KCS, which suggests that other mechanisms may be involved in the pathogenesis of this manifestation. Additionally, PVL may be a marker of KCS development in these patients.     

Genetic evidence of transmission of human T cell lymphotropic virus type 1 between spouses

Sexual transmission of human T cell lymphotropic virus type 1 (HTLV-1) is considered to be an important route of infection in adults. However, no direct evidence has been reported that supports this observation. To address this issue, sequence variations of the gp46 (envelope)-coding region of HTLV-1 were determined in 13 patients infected with HTLV-1 who experienced seroconversion and in their spouses. Twenty-two nucleotide changes that were different from the reference sequence of lambdaATK-1 were identified. However, the gp46 sequences found were identical within each married couple. HTLV-1 proviral DNA loads measured in 11 of these couples varied from 10 to 3430 copies per 10(5) PBMC, and the proviral DNA loads of spouses often differed. This study provides the first genetic confirmation of the transmission of HTLV-1 from a carrier spouse to his/her partner. The findings also suggest that host-related factors play a more important role than do virus-specific factors in determining HTLV-1 proviral DNA load.     

Immunopathogenesis of human T cell lymphotropic virus type I-associated neurologic disease

This review focuses on current approaches to understanding the immunopathogenesis of human T cell lymphotropic virus (HTLV) type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) based on newly developed molecular and immunologic techniques that have been adapted to studies of HTLV-I proviral load, HTLV-I mRNA, and HTLV-I tax-specific CD8 T cells. These methods enable researchers to study previously inaccessible aspects of this disease and allow a more detailed analysis of virus/host immune responses as they relate to disease specificity in this disorder. The role of HTLV-I-specific CD8 T cell immune responses is highlighted. The elucidation of the immunopathology of HAM/TSP will enhance our understanding of other HTLV-I-associated disorders plus other neurologic, hematologic, and inflammatory diseases for which viral etiologies have been suggested.     

Clonal expansion of limited T cell clonotypes in affected muscle from a patient with post-transplant polymyositis

Critical roles of T cells in idiopathic polymyositis have been suggested, but, those in polymyositis occurring as GVHD after BMT are poorly understood. We thus investigated T cell clonality in a patient with post- transplant polymyositis. As a result, T cell receptor beta chains used various BV families in peripheral blood, but only one BV family (BV7) in affected muscle. Importantly, T cells proliferated oligoclonally both in the peripheral blood and the muscle, however, the expanded clonotypes were completely different. Taken together, T cells expanded in the muscle, possibly stimulated by limited kinds of antigens, may drive myositis.     

Cervical shedding of human T cell lymphotropic virus type I is associated with cervicitis

Human T cell lymphotropic virus type I (HTLV-I) is sexually transmitted. The purpose of this study was to determine the prevalence and risk factors for cervical shedding of HTLV-I DNA among Peruvian sex workers. HTLV tax DNA was detected in cervical specimens from 43 (68%) of 63 HTLV-I-infected sex workers and in samples obtained during 113 (52%) of 216 clinic visits between 1993 and 1997. Detection of HTLV DNA was associated with the presence of > or =30 polymorphonuclear cells (PMNs) within cervical mucus per 100x microscopic field (odds ratio [OR], 4.3, 95% confidence interval [CI], 1.8-10.1) and with the presence of cervical secretions (OR, 2.0; 95% CI 1.2-3.4). Hormonal contraceptive use (OR 1.7; 95% CI, 0.8-3.6) and concomitant cervical infection by Chlamydia trachomatis (OR, 1.5; 95% CI, 0.3-4.3) or Neisseria gonorrhoeae (OR, 1.1; 95% CI, 0.6-3.7) were not significantly associated with HTLV-I shedding. Our results suggest that cervicitis may increase cervical HTLV-I shedding and the sexual transmission of this virus.     

Maternal proviral load and vertical transmission of human T cell lymphotropic virus type 1 in Guinea-Bissau

The relative importance of routes of transmission of human T cell lymphotropic virus type 1 (HTLV-1) in Guinea-Bissau is largely unknown; vertical transmission is thought to be important, but there are very few existing data. We aimed to examine factors associated with transmission in mothers and children in Guinea-Bissau, where HTLV-1 is endemic (prevalence of 5% in the adult population). A cross-sectional survey was performed among mothers and their children (aged <15 years) in a rural community in Guinea-Bissau. A questionnaire to identify risk factors for infection and a blood sample were obtained. HTLV-1 proviral load in peripheral blood was determined and PCR was performed to compare long terminal repeat (LTR) sequences in mother-child pairs. Fourteen out of 55 children (25%) of 31 HTLV-1-infected mothers were infected versus none of 70 children of 30 uninfected mothers. The only factor significantly associated with HTLV-1 infection in the child was the proviral load of the mother; the risk of infection increased significantly with the log(10) proviral load in the mother's peripheral blood (OR 5.5, 95% CI 2.1-14.6, per quartile), adjusted for weaning age and maternal income. HTLV-1 sequences of the LTR region obtained from mother-child pairs were identical within pairs but differed between the pairs. Vertical transmission plays an important role in HTLV-1 transmission in this community in Guinea-Bissau. The risk of transmission increases with the mother's proviral load in the peripheral blood. Identical sequences in mother-child pairs give additional support to the maternal source of the children's infection.     

Detection of human T lymphotropic virus type I proviral DNA in patients with diffuse panbronchiolitis

Abstract In Japan a number of reported cases of diffuse panbronchiolitis (DPB) have been associated with human T lymphotropic virus type I (HTLV-I) infection. In this study the hypothesis that HTLV-I proviral DNA may be prevalent in DPB was examined using polymerase chain reaction (PCR) for the region of env or the two-step PCR for the pX region of this virus. The presence of HTLV-I proviral DNA was studied in the peripheral blood mononuclear cells (PBMC) obtained from 10 patients with DPB. The presence of proviral DNA in PBMC in 12 patients with chronic obstructive pulmonary disease (COPD), eight patients with idiopathic interstitial pneumonia (IIP), four patients with bronchiectasis, 12 patients with bronchogenic carcinoma and 47 subjects without pulmonary diseases were also studied as relevant controls. The lung tissue obtained from 11 patients with DPB, 12 patients with diffuse aspiration bronchiolitis (DAB) at autopsy, and the surgical lung samples obtained from 12 patients with bronchogenic cancer were also studied. Peripheral blood mononuclear cells obtained from one DPB patient and one bronchogenic carcinoma patient were positive for the HTLV-I pX region. The presence of the pX region was also found in the lung tissue of three DPB patients (27.3%) and one DAB patient (8.3%). None of other subjects were positive for HTLV-I proviral DNA. In conclusion, HTLV-I is not the causative virus in the pathogenesis of COPD, IIP bronchiectasis and bronchogenic carcinoma. There is a likelihood that HTLV-I infection is associated with some cases of DPB; however, this association needs further verification.     

Clinical manifestations of human T lymphotropic virus type I-infected patients with systemic lupus erythematosus

OBJECTIVE: Human T lymphotropic virus type I (HTLV-I) may be associated with some connective tissue autoimmune diseases, including systemic lupus erythematosus (SLE). To determine the relationship between HTLV-I infection and SLE, we examined the clinical manifestations of SLE patients with HTLV-I infection. METHODS: Eighty-nine patients with SLE were screened for antibodies to HTLV-I by electrochemiluminescence immunoassay. The presence of HTLV-I proviral sequences in peripheral blood mononuclear cells (PBMC) was determined by real-time polymerase chain reaction (PCR) quantification and Southern blotting analysis. The differences in clinical manifestations between HTLV-I-seropositive and seronegative patients with SLE were analyzed statistically. RESULTS: Fourteen of 89 (15.7%) patients were HTLV-I seropositive. All PBMC samples from 11 patients tested by PCR and 3 samples from 10 patients tested by Southern blotting analysis were positive for HTLV-I-related sequences. The age of HTLV-I-seropositive patients with SLE was significantly higher than that of seronegative patients (median 60 vs 42 yrs; p < 0.0005). The age at onset of SLE in HTLV-I-seropositive patients was also significantly higher than that of seronegative patients (median 45.5 vs 30 yrs; p <0.0005). The lymphocyte count in HTLV-I-seropositive SLE patients was significantly higher than that of seronegative patients (median 1740 vs 1066/microl; p = 0.027). The maintenance dose of prednisolone in HTLV-I-seropositive patients with SLE was significantly lower than that in seronegative patients (median 5 vs 9 mg/day; p = 0.012). CONCLUSION: This is the first report of the differences in clinical manifestations between SLE patients with and without HTLV-I infection. Our results suggest some involvement of HTLV-I in the pathogenesis of SLE.     

Envelope sequence variation and phylogenetic relations of human T cell lymphotropic virus type 1 from endemic areas of Colombia

The HTLV-1 envelope gene of 12 TSP/HAM patients from two endemic areas of southwest Colombia (Tumaco and Buenaventura) was amplified by nested PCR, sequenced, and compared with previously reported HTLV-1 envelope sequences from isolates worldwide. In general, the sequence divergences among all Colombian samples ranged from 0.1 to 1.6%. Some amino acid substitutions, referring to the ATK-1 prototype strain in the surface domain gp46 and in p21, were highly prevalent in southwest Colombia, suggesting a geographical clustering of mutations in the envelope gene. The phylogenetic analysis showed that the Colombian isolates belong to the HTLV-1a lineage with minor subgroups. The genetic distance between Colombian and Japanese isolates ranged from 0.1 to 1.8%; in comparison, the genetic distance between Colombian and Caribbean isolates ranged from 0.4 to 2.2%. Our results strongly suggest that the actual quasispecies populations in southwest Colombia have been generated by separate, differently timed introductions of virus.     

Immunological and virological status of a hemophiliac infected with human T cell lymphotropic virus type 1 and human immunodeficiency virus type 1, and results of therapy

The immunological and virological status of three hemophiliacs infected with human immunodeficiency virus type 1 (HIV-1) was monitored for 11 months. One of these patients was also infected with human T cell lymphotropic virus type 1 (HTLV-1), and HIV-1 could be isolated only from this patient among the three subjects. The doubly infected subject had the fewest T4 (helper) lymphocytes and the highest proportion of T8 lymphocytes with DR human leukocyte antigens (DR-Ag). The serum level of HIV-1 antigen increased in this patient during the observation period, and this increase was accompanied by a decrease in the proportion of DR-Ag-positive cells among the T8 lymphocytes. This patient was treated with 800 mg of zidovudine daily for 50 days. With treatment, the nonspecific clinical symptoms improved and the proportions of DR-Ag positive cells among the T8 lymphocytes decreased. Serum levels of HIV-1 antigen decreased immediately when therapy was started but later increased during therapy. In persons infected with both HTLV-1 and HIV-1, HIV-1 seems to proliferate readily.