RESUMO
Adult 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.
Assuntos
Anticorpos Antivirais/sangue , Biomarcadores/sangue , Infecções por HTLV-I/sangue , Leucemia-Linfoma de Células T do Adulto/sangue , Paraparesia Espástica Tropical/sangue , Adolescente , Adulto , Idoso , Antígenos Virais/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Imunoprecipitação , Jamaica , Leucemia-Linfoma de Células T do Adulto/imunologia , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/imunologia , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: Few studies have specifically examined proviral load (PVL) and clonal evolution of human T-lymphotropic virus type 1 (HTLV-1)-infected cells in vertically infected children. METHODS: Sequential samples (from ages 1 to 16 years) from 3 HTLV-1-infected children (cases A, B and C) in the Jamaica Mother Infant Cohort Study were analyzed for their PVL and clonal expansion of HTLV-1-infected cells in peripheral blood mononuclear cells (PBMCs) by inverse-long PCR. RESULTS: The baseline PVL (per 100,000 PBMCs) of case A was 260 (at 1 year of age) and of case B it was 1,867 (at 3 years of age), and they remained constant for more than 10 years. Stochastic patterns of clonal expansion of HTLV-1-infected cells were predominately detected. In contrast, case C, who had lymphadenopathy, seborrheic dermatitis and hyperreflexia, showed an increase in PVL from 2,819 at 1.9 years to 13,358 at 13 years of age, and expansion of 2 dominant clones. CONCLUSION: The clonal expansion of HTLV-1-infected cells is induced in early childhood after infection acquired from their mothers. Youths with high PVL and any signs and symptoms associated with HTLV-1 infection should be closely monitored.
Assuntos
Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/classificação , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Provírus/classificação , Provírus/isolamento & purificação , Carga Viral , Adolescente , Criança , Pré-Escolar , Impressões Digitais de DNA , DNA Viral/genética , Feminino , Infecções por HTLV-I/transmissão , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Lactente , Jamaica , Leucócitos Mononucleares/virologia , Estudos Longitudinais , Reação em Cadeia da Polimerase/métodos , Provírus/genéticaRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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."
Assuntos
Aleitamento Materno , Genes MHC Classe I , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/transmissão , Transmissão Vertical de Doenças Infecciosas , Pré-Escolar , Feminino , Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Jamaica , Provírus/isolamento & purificação , Fatores de Risco , Fatores SocioeconômicosRESUMO
In a recent clinical analysis of 308 Jamaican children, human T lymphotropic virus type I (HTLV-I) infection was found to be associated with significantly higher incidence rates of seborrheic dermatitis, eczema, and persistent hyperreflexia of the lower limbs and with nonsignificantly increased rates of severe anemia and abnormal lymphocytes. Results of examination of HTLV-I viral markers in the 28 HTLV-I-infected children provided virologic support for the epidemiologic associations of HTLV-I with seborrheic dermatitis and severe anemia in childhood.
Assuntos
Anemia/etiologia , Dermatite Seborreica/etiologia , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Provírus/isolamento & purificação , Anemia/epidemiologia , Biomarcadores/sangue , Pré-Escolar , Estudos de Coortes , Comorbidade , Dermatite Seborreica/epidemiologia , Progressão da Doença , Infecções por HTLV-I/sangue , Infecções por HTLV-I/epidemiologia , Humanos , Incidência , Lactente , Jamaica/epidemiologia , Fatores de Risco , Carga ViralRESUMO
OBJECTIVE: Human T-cell lymphotropic virus type I (HTLV-I) infection in childhood is believed to play an important role in risk for adult T-cell leukemia/lymphoma. Although HTLV-I is known to be associated with infective dermatitis in childhood, other HTLV-I-associated morbidity in children has not been well studied. We sought to determine the HTLV-I-associated health effects in Jamaican children. METHODS: We compared incidence rates of several health outcomes in 28 HTLV-I-infected and 280 uninfected children clinically followed from age 6 weeks to a maximum of 10 years. Cox proportional hazards regression analysis was used to analyze these prospectively collected data, adjusting for confounding effects of other variables as necessary. RESULTS: HTLV-I-infected children had significantly higher incidence rates of seborrheic dermatitis (rate ratio [RR] = 4.8, 95% confidence interval [CI] = 1.9-12.5), eczema (RR = 3.1, CI = 1.2-7.9) and persistent hyperreflexia (RR = 3.7, CI = 1.6-8.2). Additionally, HTLV-I infected children had increased rates of severe anemia (RR = 2.5, CI = 0.8-7.9) and abnormal lymphocytes (RR = 2.4, CI = 0.8-7.6) that were of borderline statistical significance. CONCLUSIONS: Our study suggests that HTLV-I-associated skin diseases of childhood may include seborrheic dermatitis and eczema. Additionally, these data suggest that persistent hyperreflexia of the lower limbs may be an early sign of HTLV-I-associated neurologic involvement in children. Expansion and continued clinical observation of this cohort would be valuable.
Assuntos
Anemia/etiologia , Dermatite Seborreica/etiologia , Eczema/etiologia , Infecções por HTLV-I/complicações , Reflexo Anormal , Anemia/epidemiologia , Aleitamento Materno , Estudos de Coortes , Dermatite Seborreica/epidemiologia , Eczema/epidemiologia , Infecções por HTLV-I/fisiopatologia , Incidência , Jamaica/epidemiologia , Exame Neurológico , Modelos de Riscos ProporcionaisRESUMO
In a prospective study involving 150 mothers and their offspring in Jamaica, we examined maternal viral factors associated with the risk of transmission of human T lymphotropic virus type 1 (HTLV-1). Overall, the incidence of HTLV-1 infection among children was 8.3 occurrences per 1000 person-months. A higher maternal provirus level (odds ratio [OR], 1.9 per quartile) and a higher HTLV-1 antibody titer (OR, 2.2 per quartile) were independently associated with transmission to children, whereas the presence of anti-Tax antibody was not. Higher maternal antibody titers also were associated with older age at infection among children who were breast-fed for
Assuntos
Produtos do Gene tax/imunologia , Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/transmissão , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Transmissão Vertical de Doenças Infecciosas , Adolescente , Adulto , Fatores Etários , Biomarcadores , Aleitamento Materno , Feminino , Infecções por HTLV-I/imunologia , Humanos , Jamaica/epidemiologia , Estudos Prospectivos , Provírus , Carga ViralAssuntos
Criança , Pré-Escolar , Humanos , Masculino , Relatos de Casos , Infecções por HTLV-I/complicações , Dermatite/etiologia , Relação CD4-CD8 , Dermatite/imunologia , Seguimentos , Haplótipos , Antígenos HLA , Infecções por HTLV-I/imunologia , Imunoglobulinas/sangue , Estudos Prospectivos , Subpopulações de Linfócitos TRESUMO
Mother-to-child transmission of human T-cell lymphotrophic virus type 1 (HTLV-I) is primarily due to prolonged breast-feeding (>6 months) in the post-natal period. Most infant infections are not identifiable until 12-18 months of age by available whole virus Western blot serologic tests because of their inability to distinguish passively transferred maternal antibody from infant antibody. We investigated two methods to assess more accurately the time of infant infection. In prospectively collected serial biospecimens, HTLV-I-specific immunoglobulin (Ig) isotypes of IgM and IgA were determined by Western blot and HTLV-I proviral DNA was detected by polymerase chain reaction (PCR). IgA and IgG reactivity was assessed in periodic serum samples from 16 HTLV-I-seropositive children while IgM reactivity was observed in 100 percent of children at 24 months of age and 73 percent of children at 6-12 months of age; however, this could represent maternal and not infant antibody. Both IgA and IgM reactivity were insensitive indicators of infection, with only 50 percent of children showing reactivity at 24 months of age. PCR testing was performed in biospecimens obtained from 11 of these children. An estimated median time of infection of 11.9 months was determined by PCR, which was similar to the median time to infection determined by whole virus Western blot (12.4 months; P=0.72). PCR Tests support a median time to infection that is similar to that estimated by whole virus Western blot. (AU)
Assuntos
Adulto , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Lactente , Aleitamento Materno , Transmissão Vertical de Doenças Infecciosas , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Infecções por HTLV-I/transmissão , DNA Viral/análise , Estudo de Avaliação , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/virologia , Anticorpos Anti-HTLV-I/sangue , Imunoglobulina A/sangue , Imunoglobulina M , Jamaica , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , Provírus , Fatores de TempoRESUMO
Objectives: To define the clinical and laboratory features associated with infective dermatitis (ID) and confirm its association with human T-lymphotropic virus type 1 (HTLV-I). Design: A case series of patients with ID were compared with patients with atopic dermatitis (AD) which is an important disease in the differential diagnosis of ID. Setting: Patients were recruited from dermatology and pediatric clinics at the University Hospital of the West Indies and the Bustamante Children's Hospital, Kingston, Jamaica. Main Outcome Measures: Clinical and laboratory features of patients with AD were compared with those of patients with ID. Patients: Consecutive patients older than 1« years diagnosed as having ID (n=50) and AD (n=35) were enrolled based on clinical findings. Results: The mean age of patients with ID and AD were 6.9 and 7.8 years, respectively. Histologically, both disease were predominantly chronic dermatitis... Conclusion: Infective dermatitis is a distinct clinical entity associated with HTLV-I, which plays a role in the pathogenesis and immune perturbations observed.(AU)