Human T-cell Lymphotropic Virus Type I Antibody Research Articles

Quantitative differences in HTLV-I antibody responses: classification and relative risk assessment for asymptomatic carriers and ATL and HAM/TSP patients from Jamaica

AbstractAdult T-cell leukemia (ATL) and human T-cell lymphotropic virus type I (HTLV-I)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) are known to be caused by HTLV-I infection. However, current methods used to determine HTLV-I infection do not differentiate between HTLV-I asymptomatic carriers (ACs) and ATL and HAM/TSP patients. Using the luciferase immunoprecipitation system, a highly sensitive, quantitative technology that can efficiently detect HTLV-I Ab responses, we examined Ab responses for HTLV-I in serum/plasma samples from 439 subjects in Jamaica, including HTLV-I–seronegative donors, ACs, and ATL and HAM/TSP patients. The Ab responses of HTLV-I–infected subjects differed significantly from those of seronegative donors for all 3 immunodominant proteins, Gag, Env, and Tax. HAM/TSP patients had significantly higher Ab responses for Gag and Env compared with ACs, and Ab responses for all 3 Ags were higher in HAM/TSP patients than in ATL patients. Moreover, immunoreactivities for HTLV-I Ags as determined by the luciferase immunoprecipitation system could distinguish HAM/TSP patients from ACs at a true-positive rate of 85.42% and from ATL patients at a true-positive rate of 75.00%, and modeled in conjunction with subject information to distinguish HAM/TSP patients from ACs (odds ratio = 14.12) and from ATL patients (odds ratio = 7.00). The relative risk assessment resulting from these significant differences between Ab responses in HTLV-I–infected groups may be a useful diagnostic tool in the future.

Clinical and demographic features of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Rio de Janeiro, Brazil.

In Rio de Janeiro (RJ) most cases of paraparesis of obscure origin are associated with the human T-cell lymphotropic virus type I (HTLV-I). Thirty-four consecutive patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) from RJ were evaluated. Most patients came from low socio-economic levels. There was no difference in terms of gender. The main affected racial group was white. A history of sexually transmitted diseases was a major risk factor for HAM/TSP and a positive serology for syphilis was found in 26.5% of the patients. The major clinical findings were of a spastic paraparesis with generalized brisk tendon jerks and bilateral Babinki's sign. Sensation was abnormal in 25 patients (73.5%) and five (14.7%) had a sensory level. Three patients (8.8%) had optic atrophy. The cerebrospinal fluid showed a lymphocytic pleocytosis with a mean total protein content of 0.4 g/litre, and an increased intrathecal IgG synthesis in 59.4% of patients. HAM/TSP and multiple sclerosis (MS) occur indigenously in RJ and some HAM/TSP cases can be sometimes confused with MS. Therefore we propose that, in places where MS coexist with HAM/TSP, HTLV-I antibodies should be sought routinely in those MS suspected cases with prominent spastic paraparesis.

Human Leukocyte Antigen Concordance and the Transmission Risk via Breast‐Feeding of Human T Cell Lymphotropic Virus Type I

We examined the association between mother-to-child human T cell lymphotropic virus type I (HTLV-I) transmission and human leukocyte antigen (HLA) class I types. In 1989, children born to HTLV-I-infected mothers in Jamaica were enrolled and prospectively evaluated for HTLV-I infection. HLA class I types in mothers and children were determined by DNA-based polymerase chain reaction methods. Associations between HLA class I types and transmission of HTLV-I were analyzed using proportional-hazards regression models adjusted for the duration of breast-feeding. Transmission risk in children still breast-feeding at 12 months was determined using actuarial methods. Of 162 children, 28 (17%) became infected. After Bonferroni's adjustment for multiple comparisons, the transmission risk was not influenced by any specific HLA class type or the A2 supertype. However, compared with children who shared 3 HLA class I types with their mothers (the minimum number possible), the transmission risk increased 1.8-fold with 4 shared types and 3.0-fold with 5 or 6 shared types (Ptrend = .039; 1.75-fold increase for each additional concordant HLA type). This association was independent of maternal HTLV-I proviral level, antibody titer, and household income. We found a significant dose-response relationship between HTLV-I transmission via breast-feeding and mother-child HLA class I type concordance. Immunological interactions between a child's cells and maternal cells may influence the risk of HTLV-I infection by breast-feeding, perhaps because antigens on maternal cells are seen by the child as being "self."

Immune response against the exp-1 protein of Plasmodium falciparum results in antibodies that cross-react with human T-cell lymphotropic virus type 1 proteins.

To examine the role of the Plasmodium falciparum Exp-1 blood-stage protein in producing antibodies that cross-react with human T-cell lymphotropic virus type I (HTLV-I) proteins, we studied sera from Indonesian volunteers who seroconverted to malaria after transmigrating to an area where malaria is hyperendemic. Samples from Philippine volunteers, that were used in a prior study that examined malaria antibodies that cross-react with HTLV-I proteins, were also used. Eighty-three percent of the Indonesian transmigrants developed antibodies against the malaria Exp-1 protein by 6 months postmigration. Of these malaria seroconverters, 27% developed false-positive HTLV-I enzyme immunoassay (EIA) immunoreactivity, as indicated by indeterminate HTLV-I Western blot banding patterns. Five of the six Philippine samples tested were HTLV-I EIA false positive and Western blot indeterminate. When a recombinant Exp-1 protein was used in blocking experiments, the HTLV-I Western blot immunoreactivity of sera from both groups was either completely eliminated or greatly reduced. No effect on the Western blot immunoreactivity of truly HTLV-I-positive sera was seen. To determine if immunization with the recombinant Exp-1 protein could elicit the production of HTLV-I antibodies, six mice were inoculated with the recombinant protein. Following administration of three 50-microgram doses of the protein, four of the six mice developed antibodies that cross-reacted with HTLV-I proteins on Western blot. These results indicate that the immune response against the malaria Exp-1 protein may result in HTLV-I-cross-reacting antibodies that can lead to false-positive EIA and indeterminant Western blotting results.

Seroepidemiological Prevalence of Human T-Cell Lymphotropic Virus Type I (HTLV-I) among Healthy Blood Donors in Eastern Saudi Arabia

Seroepidemiological Prevalence of Human T-Cell Lymphotropic Virus Type I (HTLV-I) among Healthy Blood Donors in Eastern Saudi Arabia

Human T-cell lymphotropic virus type I-associated facial nerve palsy in Trinidad and Tobago.

To assess the association of the human T-cell lymphotropic virus type I (HTLV-I) and idiopathic facial nerve palsy of the lower motor neuron type, we studied 78 patients consecutively admitted to the Port of Spain General Hospital in Trinidad, the West Indies, with a confirmed diagnosis of idiopathic facial nerve palsy. Patients were compared with two control groups: a population-based group of persons 20 years and older and a hospital-based group of patients 15 to 84 years old admitted to the medical wards. Sixty-two patients were Trinidadians of African origin and 16 were Trinidadians of East Indian origin. None of the East Indian patients was HTLV-I antibody positive. Three Afro-Trinidadians were infected with human immunodeficiency virus type 1 and 1 was coinfected with this virus and HTLV-I. Of the remaining 58 Afro-Trinidadians, 12 (20.7%) were HTLV-I positive only. This rate was statistically higher than the HTLV-I seroprevalence in the Afro-Trinidadian general population (3.5%) and the hospital control group (5.6%). After age standardization, the HTLV-I prevalence for patients with facial nerve palsy remained significantly elevated. HTLV-I antibody assays should be performed on all patients with idiopathic facial nerve palsy of the lower motor neuron type who live in HTLV-I endemic areas or are migrants from these areas.

Is screening of Australian blood donors for HTLV-I necessary?

To re-examine the 1992 decision by Australian Red Cross for its blood banks to screen blood donors for antibody to human T-cell lymphotropic virus type I (HTLV-I) by determining the risk of its transmission by blood transfusion. Data on patterns of return behaviour by repeat blood donors in Victoria were modelled to deduce the number of donors giving repeat donations in Australia from March 1993 to December 1995. Data on annual donor and issued cellular blood products from 1992 to 1995 were obtained from national Red Cross statistics. From the numbers of donations given by repeat donors, together with the number of new donors, the number tested for HTLV-I was deduced. The number and characteristics of donors screened positive for HTLV-I antibody were collated. The crude prevalence of HTLV-I was calculated by dividing the number of donors with HTLV-I by the total number of donors (repeat donors and new donors). The incidence of HTLV-I was calculated by dividing the number of seroconversions in repeat donors by the cumulative period of donor exposure. Sixteen homologous and five autologous donors were found to be positive for HTLV-I; none seroconverted and no clear risk factors for HTLV-I were identified. The prevalence of HTLV-I in Australian donors is 1 in 100,000 and the incidence less than 1 in 1 million person-years. In the absence of HTLV-I screening, the calculated risk of a transfused patient developing HTLV-I infection is 1 in 370,000, with a risk of developing HTLV-I disease of 1 in 9 to 15 million. Three possible future courses of action for screening for HTLV-I are to screen every donation, to screen only new donors or to discontinue screening altogether. Using the information in this study, public discussion should be encouraged to assist stakeholders to agree on an acceptable level of risk and an appropriate level of screening for HTLV-I in Australia.

Anesthetic Considerations in Myelopathy Associated with Human T-Cell Lymphotropic Virus Type I (HTLV-I-Associated Myelopathy

Anesthetic Considerations in Myelopathy Associated with Human T-Cell Lymphotropic Virus Type I (HTLV-I-Associated Myelopathy

Findings from the Miyazaki Cohort Study.

The purpose of the Miyazaki Cohort Study is to describe and analyze the natural history of human T-cell lymphotropic virus type I (HTLV-I) in a highly endemic population in southwestern Japan. As of August 1995, 1,960 individuals have been enrolled, of whom 27% were HTLV-I antibody positive at baseline. Our achievements over the past decade of following this cohort include the identification of several viral markers that characterize high-risk carriers and the documentation that carriers have subclinical evidence of impaired cellular immunity. We have begun to estimate the impact of the infection on the health of carriers and have found that men are at greater risk of HTLV-I-associated diseases than women. We have been able to identify prospectively risk factors associated with sexual transmission. Most important, by identifying subclinical markers of pathogenesis, we hope to provide the foundation for developing interventions to prevent HTLV-I-associated disease.

Markers of health status in an HTLV-I-positive cohort.

The health effects of chronic human T-cell lymphotropic virus type I (HTLV-I) infection were examined in a cohort of Japanese men who had emigrated from Okinawa, Japan, and had been participants in a prospective study in Hawaii since 1965. In the present follow-up study carried out in 1987-1988, various health indicators were measured in the subjects, whose mean age was 72.5 years. Participation rates were lower in the HTLV-I seropositives than in the seronegatives (46.7% vs. 76.0%) in the > or = 75-year age group. Lack of participation was significantly correlated with a high HTLV-I antibody titer. Among the participants, seropositive subjects were significantly more likely than the seronegatives to have lymphocytopenia (32.7% vs. 17.7%) and mild anemia (25.5% vs. 14.1%) after adjustment for age and socioeconomic status. The seropositives also had a higher frequency of acupuncture therapy (age-adjusted odds ratios were 2.1 and 4.2 for 1-5 treatments and > or = 6 treatments, respectively). Proportions of subjects who had been hospitalized at least twice were higher among the seropositives in the oldest age groups, 70-74 years and > or = 75 years, but not in those aged 65-69 years. Although specific disease conditions were not identified in this study, hematologic data, treatment histories, and the correlation between participation status and HTLV-I antibody titers suggest that chronic HTLV-I infection may be associated with as yet undefined adverse health effects, particularly in older age groups.

Declining Seroprevalence and Transmission of HTLV-I in Japanese Families Who Immigrated to Hawaii

This study examined the seroprevalence and transmission of human T cell lymphotropic virus type I (HTLV-I) in Japanese families who originated in Okinawa, an area in which HTLV-I is endemic, and who were currently residing in Hawaii, a nonendemic area. Among a cohort of Japanese men whose sera were collected in Hawaii in 1967-1975, those of Okinawan ancestry had an HTLV-I seroprevalence of 11.4%. This study, conducted in 1987-1988, sampled 142 index subjects from this male cohort and tested them along with their wives, children, and spouses of the children for HTLV-I antibodies. Seropositivity in their wives was 11.4% and 41.2% among the seronegative and seropositive index subjects, respectively; seropositivity also increased from 29.4% to 35.3% to 58.8% with the husbands' increasing antibody levels by tertiles. Elevated antibody levels may be a marker for infectivity, which is associated with more efficient sexual transmission of HTLV-I. The age-adjusted odds ratio for the association of seropositivity between husband and wife, however, was four times lower than that reported among native Okinawans. In addition, a substantially low seroprevalence (1.3%) was found among their offspring. The decline in HTLV-I transmission in this migrant population may be due to low infectivity in the parent generation who live in a nonendemic environment, increasing numbers of offspring marrying outside of the Okinawan community, and improved living circumstances.

Detection and differentiation of antibodies to human T-cell lymphotropic virus types I and II by the immunofluorescence method

We compared the sensitivities of the prototype human T-cell lymphotropic virus type I (HTLV-I)- and HTLV-II-transformed cell lines, MT2 and Mo-T, with that of an HTLV-II-infected cell line, clone 19, established in our laboratory, in the immunofluorescence (IF) test for detection of antibody to HTLV-I and HTLV-II. In addition, IF antibody titers with the three antigens were determined, and the results were compared with HTLV-I and HTLV-II typing by polymerase chain reaction (PCR). The MT2 cell line was more sensitive than the two HTLV-II cell lines for detecting HTLV-I antibody by IF, and clone 19 was more sensitive than Mo-T or MT2 for measuring HTLV-II antibody. In the titration study, the antigen that gave the highest titer correlated completely with the HTLV type determined by PCR, indicating that the relatively simple IF titration method can be used for differentiating HTLV-I and HTLV-II antibody in sera and plasmas.

Human T-Lymphotropic Virus Type I (HTLV-I) Seroprevalence in Jamaica

An island-wide cohort of 13,260 Jamaicans who applied for food-handling licenses during 1985 and 1986 were tested for antibodies to human T-cell lymphotropic virus type I (HTLV-I). Demographic and residence history data were linked to geographic and ecologic measures of elevation, rainfall, crop-growing areas, population density, and additional measures of urbanization and correlated with HTLV-I antibody status. By logistic regression analysis (performed separately for men and women), men and women who currently resided at low elevation (less than or equal to 1,000 ft (305 m)) were more likely to be HTLV-I infected than were those residing at high elevation. Men, but not women, who were born in citrus-growing areas were more likely to be HTLV-I infected than were men who were born in other areas. By univariate analysis, there was a significant positive trend of increasing HTLV-I seroprevalence with increasing amount of annual rainfall associated with birthplace and primary residence areas. However, these associations did not remain significant after adjusting for age and sex. These environmental associations raise the possibility of new modes of viral transmission or host response to infection, although they may simply be surrogates for socioeconomic status, breastfeeding habits, or sexual behavior, which are known determinants of HTLV-I zero prevalence.

Human T-Cell Lymphotropic Virus Type I and Neurologic Disease in Panama, 1985 and 1986

Human T-cell lymphotropic virus type I (HTLV-I) causes adult T-cell leukemia and has recently been associated with HTLV-associated myelopathy/tropical spastic paraparesis. The HTLV-I is endemic throughout the Caribbean basin and parts of South America, and HTLV-associated myelopathy/tropical spastic paraparesis also seems to be common in this area. This 2-year study, 1985 and 1986, was designed to evaluate the occurrence of HTLV-I infection in all newly diagnosed cases of selected neurologic diseases in Panama City, Panama. Six (8%) of 71 patients had antibody to HTLV-I detected by immunofluorescence, enzyme-linked immunosorbent assay, radioimmunoassay, and Western blot assays; 5 patients' conditions were diagnosed as spastic paraparesis, and all 5 were seropositive and also had HTLV-I antibody in cerebrospinal fluid. The remaining seropositive patient had multiple sclerosis, and no antibody was detected in her cerebrospinal fluid. Clinical and electrophysiologic studies indicated that HTLV-I-associated spastic paraparesis is a multifocal, primarily demyelinating disease that principally involves the spinal cord.

Human T Cell Lymphotropic Virus Type I (HTLV-I) among Female Prostitutes in Kinshasa, Zaire

Three hundred seventy-seven prostitutes from Kinshasa, Zaire, were enrolled in a study to determine associated risk factors for human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic virus type I (HTLV-I) infection. Twelve samples (3.2%) were seropositive for HTLV-I; results for HIV-1 (101 [26.8%]) are reported elsewhere. HTLV-I prevalence increased with age, and seven of the seropositive women originated from the Equateur region, a remote area in northwestern Zaire. The prevalence among women from Equateur (7.2%) was higher than that of women from all other regions (1.8%, P = .02). Presence of HTLV-I antibodies was not associated with frequency or type of sex practice. In a subsequent study, 350 serum samples were obtained from a variety of subjects in the Equateur region in 1986. Nineteen (5.4%) showed antibodies to HTLV-I. These data and a recent report of a cluster of patients with tropical spastic paraparesis from this region suggest that HTLV-I is endemic in the Equateur region of Zaire.

Evaluation of a HTLV‐1 Subunit Vaccine in Prevention of Experimental STLV‐I Infection in Macaca nemestrina

Pig-tailed macaques were vaccinated with a human T-cell lymphotropic virus type I (HTLV-I) subunit vaccine. Vaccinates and controls were challenged with simian T-cell lymphotropic virus type I (STLV-I)-infected cells. Vaccination yielded antibody responses to HTLV-I and STLV-I gag and env precursors. Controls developed HTLV-I and STLV-I antibody to gag and tax protein. Immunization produced syncytium inhibiting antibody and cellular cytotoxicity to virus-infected cells. Reverse transcriptase activity was present in control macaques only, implying that the subunit vaccine was protective against STLV-I infection.

Characterization of antibody reactivity to human T-cell lymphotropic virus types I and II using immunoblot and radioimmunoprecipitation assays

We have characterized the immunoreactivity to human T-cell lymphotropic virus type I (HTLV-I) among 26,983 persons of various seroprevalence groups by using enzyme immunoassay, immunoblot (IB), and radioimmunoprecipitation assays (RIPA) in accordance with Public Health Service recommended guidelines for the interpretation of serologic test results for HTLV-I infection. IB-indeterminate serum specimens (n = 178) were reactive to HTLV-I gag proteins, and no serum contained only env reactivity. Overall, RIPA resolved 40% of IB-indeterminate serum samples; however, the probability that RIPA would confirm IB-indeterminate samples depended on the seroprevalence of the population tested. HTLV-I gag p19-only reactivity on IB was not a reliable marker of HTLV-I infection, while gag p24 reactivity on IB was clearly associated with positive seroreactive specimens. IB and RIPA tests did not clearly distinguish between HTLV-I and HTLV-II seroreactivities. These data emphasize that patterns of immunoreactivity to HTLV-I antigens are dependent upon the seroprevalence of the risk groups tested. In addition, RIPA detected antibodies to env proteins present in low titer in a substantial number of IB gag-only reactive sera and resolved the HTLV-I antibody status of these sera.

Rapid Development of Myelopathy after HTLV-I Infection Acquired by Transfusion during Cardiac Transplantation

HUMAN T-cell lymphotropic virus Type I (HTLV-I), considered to be the causative agent of adult T-cell lymphoma/leukemia,1 , 2 is also associated with a chronic myelopathy (tropical spastic paraparesis) that is endemic in the Caribbean,3 , 4 Africa,5 6 7 and South America,8 and with HTLV-I—associated neuropathy in Japan.9 HTLV-I is transmitted sexually, chiefly from men to women, from mother to child by breast-feeding, and by blood transfusion.10 , 11 In Europe and the United States, there is a low prevalence of carriers of HTLV-I antibody (less than 0.03 percent) among blood donors. The infection is found mainly in people from areas endemic for HTLV-I and among intravenous . . .

High human T-cell lymphotropic virus type I proviral DNA load with polyclonal integration in peripheral blood mononuclear cells of French West Indian, Guianese, and African patients with tropical spastic paraparesis

Human T-cell lymphotropic virus type I (HTLV-I) proviral integration status was examined by Southern blot analysis in peripheral blood mononuclear cell (PBMC) DNA from patients presenting a tropical spastic paraparesis (TSP) and serological evidence of HTLV-I infection. Surface phenotype and morphological aspects of PBMC were also studied. A polyclonal HTLV-I proviral integration was found in the PBMC of the 10 patients studied irrespective of their geographical origin (French West Indies, French Guiana, and Africa), the duration of their clinical illness, or the HTLV-I antibody titer. Furthermore, by dilution experiments and hypothesizing that only one copy of HTLV-I proviral DNA is present in one cell, we estimated that this HTLV-I integration is present in 3% to 15% of their PBMC. All 10 TSP/HTLV-I patients studied had an average of 10% of their lymphocytes abnormal, presenting either a misshapen nucleus or an adult T-cell leukemia/lymphoma (ATL)-like feature. Moreover, an elevated CD4/CD8 ratio associated with the presence of activated T cells with a high level of DR expression was observed in most patients. The significant frequency of viral-positive PBMC and the important load of HTLV-I proviral DNA that we observed in TSP/HTLV-I patients might play an important role in the pathogenesis of this recently identified clinico-virological entity.

High Human T-Cell Lymphotropic Virus Type I Proviral DNA Load with Polyclonal Integration in Peripheral Blood Mononuclear Cells of French West Indian, Guianese, and African Patients with Tropical Spastic Paraparesis

Human T-cell lymphotropic virus type I (HTLV-I) proviral integration status was examined by Southern blot analysis in peripheral blood mononuclear cell (PBMC) DNA from patients presenting a tropical spastic paraparesis (TSP) and serological evidence of HTLV-I infection. Surface phenotype and morphological aspects of PBMC were also studied. A polyclonal HTLV-I proviral integration was found in the PBMC of the 10 patients studied irrespective of their geographical origin (French West Indies, French Guiana, and Africa), the duration of their clinical illness, or the HTLV-I antibody titer. Furthermore, by dilution experiments and hypothesizing that only one copy of HTLV-I proviral DNA is present in one cell, we estimated that this HTLV-I integration is present in 3% to 15% of their PBMC. All 10 TSP/HTLV-I patients studied had an average of 10% of their lymphocytes abnormal, presenting either a misshapen nucleus or an adult T-cell leukemia/lymphoma (ATL)-like feature. Moreover, an elevated CD4/CD8 ratio associated with the presence of activated T cells with a high level of DR expression was observed in most patients. The significant frequency of viral-positive PBMC and the important load of HTLV-I proviral DNA that we observed in TSP/HTLV-I patients might play an important role in the pathogenesis of this recently identified clinico-virological entity.