RESUMO
To clarify the seroprevalence of human T-cell lymphotropic virus type I (HTLV-I) among hematologic and cancer patients in the State of Rio de Janeiro, Brazil, we investigated sera from 2430 individuals from the following groups: 152 patients with T-cell diseases, 250 with B-cell disorders, 67 with myeloid leukemia, 41 with Hodgkin's disease, 351 with a history of multiple blood transfusions, 235 patients with solid tumors of different types, and 109 family members of HTLV-I-infected patients. Antibodies to HTLV-I were screened by enzyme-linked immunosorbent assay or particle agglutination assays (or both). Repeatedly reactive samples were tested by Western blot and polymerase chain reaction assay to differentiate HTLV-I from HTLV-II. We found an increased seroprevalence rate of HTLV-I among those with lymphoid malignancies, mainly in T-cell diseases (28.9%), and these results were important in characterizing 44 cases of adult T-cell leukemia/lymphoma. We confirmed the presence of HTLV-I and HTLV-II infections in blood donors (0.4% and 0.1%, respectively), in patients exposed to multiple blood transfusions (10.2% and 0.8%, respectively), and in 30 (27.5%) of 109 family members of HTLV-I- or HTLV-II-infected patients. We also confirmed the high rate occurrence of adult T-cell leukemia/lymphoma among lymphoproliferative disorders in Rio de Janeiro, Brazil.
Assuntos
Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/epidemiologia , Doenças Hematológicas/complicações , Vírus Linfotrópico T Tipo 1 Humano , Vírus Linfotrópico T Tipo 2 Humano , Neoplasias/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doadores de Sangue , Brasil/epidemiologia , DNA Viral/análise , Feminino , Anticorpos Anti-HTLV-I/análise , Infecções por HTLV-I/complicações , Infecções por HTLV-I/imunologia , Anticorpos Anti-HTLV-II/análise , Infecções por HTLV-II/complicações , Infecções por HTLV-II/imunologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 2 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos RetrospectivosRESUMO
We describe the clinical and pathological features of 23 Afro-Caribbean patients with adult T-cell leukaemia/lymphoma admitted to the Queen Elizabeth Hospital, Barbados over a 5 year period. There were 9 males and 14 females, with a median age of 38 years (range 14-84). Twelve had acute leukaemia, 10 lymphoma (including 4 with solitary extra nodal lesions) and 1 smouldering subtype. Two patients had a past history of tropical spastic paraparesis/HTLV I associated myelopathy (TSP/HAM). The prognosis was poor, with only 3 complete responses to chemotherapy (CHOP) lasting from 9 to 36 months. We conclude that ATLL in Barbados is similar to the disease in the other Caribbean islands and Japan, except that in Barbados the age of onset is over a decade younger than in Japan.
Assuntos
Leucemia-Linfoma de Células T do Adulto/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Barbados , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/imunologia , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
We describe an unusual case of Sezary syndrome which transformed into a large T-cell non Hodgkin's lymphoma (immunoblastic) in a black man of Caribbean descent with negative HTLV-I serology and no evidence of HTLV-I infection by DNA analysis using sensitive techniques. The disease presented as a small-cell Sezary syndrome and transformed in an inguinal lymph node one year from diagnosis. Immunological markers in the small and large cells showed a mature T-cell phenotype CD4+, CD8- with expression of T-cell activation markers and a high proliferative rate. Ultrastructural analysis confirmed small Sezary cells with serpentine nucleus in the peripheral blood and immunoblasts in the lymph node. Cytogenetics demonstrated complex clonal chromosome abnormalities with involvement of 7q35, the locus for the beta chain of the T-cell receptor (TCR). Southern-blot analysis showed the same rearrangement of the TCR beta, gamma, delta chain genes in lymph node and peripheral blood cells. Antibodies to HTLV-I were not detected in the serum by ELISA and particle agglutination (PA) nor HTLV-I specific sequences were demonstrated by nested polymerase chain reaction with primers to the envelope proteins, LTR and tax/rex of HTLV-I in both tissues, blood and lymph node. The disease had an aggressive course and was refractory to therapy; the patient died of progressive disease 28 months from presentation. Two unusual features characterised this patient's illness: immunoblastic transformation of a Sezary syndrome in a patient of Afro-Caribbean origin without evidence of HTLV-I DNA sequences and negative HTLV-I serology and the atypical lymph node histology resembling ATLL.
Assuntos
Linfoma de Células T/microbiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiologia , Síndrome de Sézary/patologia , Sequência de Bases , Aberrações Cromossômicas/patologia , Bandeamento Cromossômico , Transtornos Cromossômicos , Primers do DNA/química , DNA Viral/análise , Rearranjo Gênico do Linfócito T , Genes myc , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Imunofenotipagem , Jamaica/etnologia , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL) within 4 years. Both were black of Afro-Caribbean extraction, but one had been born in the United Kingdom and had visited the Caribbean only once. Both patients were HTLV-1 seropositive, as was their mother; their father and brother were negative. The older sibling had the lymphoma form of ATLL, whilst the younger had chronic ATLL. The former was unresponsive to chemotherapy and died of progressive disease; the latter experienced transient responses to various treatments and is alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+ phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the tissues involved. This report, of the first familial ATLL in the U.K., supports the suggestion of transmission of HTLV-I from mother to child and documents the development of ATLL in second-generation Caribbean immigrants.
Assuntos
Transmissão Vertical de Doenças Infecciosas , Leucemia-Linfoma de Células T do Adulto/transmissão , Adulto , Negro ou Afro-Americano , População Negra , Antígenos CD4/sangue , Saúde da Família , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/etnologia , Leucemia-Linfoma de Células T do Adulto/patologia , Linfonodos/patologia , Linhagem , Receptores de Interleucina-2/análise , Pele/patologia , Trinidad e Tobago/etnologia , Reino UnidoRESUMO
T-cell malignancies in Brazil have a high seroprevalence rate of HTLV-I antibodies. We have analyzed the disease features in 188 Brazilian patients with a T-cell disorder. These included 40 with T-lymphoblastic leukaemia or lymphoma (T-ALL/T-LbLy) and 148 with mature T-cell diseases: 5 T-prolymphocytic leukaemia, 53 adult T-cell leukaemia/lymphoma (ATLL), 54 cutaneous T-cell lymphomas, 29 pleomorphic T-cell lymphomas and 7 large granular lymphocyte leukaemia. The diagnosis was based on clinical, morphological and immunological features and HTLV-I serology. ATLL in Brazil has the same diseases features as in other endemic regions, the only apparent differences being: age, Brazilian patients being younger than Japanese, and ethnic grouping, one third of Brazilians being white Caucasians of European descent. We applied a scoring system based on the presence or absence of typical features associated with ATLL; hypercalcaemia, cell morphology, immunophenotype, histopathology and HTLV-I status, to see whether it may help in diagnosing cases of ATLL. All had high scores, whereas all other T-cell diseases scored low. Only 5 ATLL cases were HTLV-I-negative by serology, but they had otherwise typical features of ATLL, and their cells did not have HTLV-I proviral sequences by DNA analysis. Such cases suggest that ATLL may develop in a minority of individuals living in regions where it is endemic, without evidence of HTLV-I infection, and that other factors may contribute to the pathogenesis of the disease.
Assuntos
Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia-Linfoma de Células T do Adulto/imunologia , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/virologia , Linfoma Cutâneo de Células T , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Estudos SoroepidemiológicosRESUMO
We describe the clinical and laboratory features of nine patients born in Chile with HTLV-I-positive adult T-cell leukemia/lymphoma (ATLL). All were adults (median age 51 years) of Caucasian origin without evidence of Indian or foreign extraction and none had been out of the country. The main disease features were organomegaly, cutaneous lesions, hypercalcemia and leukemia with atypical polylobed lymphocytes displaying a CD2+, CD3+, CD4+, CD8-, CD7- T-cell phenotype. Eight patients presented with acute type ATLL and one had a chronic form lasting for 16 months prior to the development of the acute phase. Lymph node histology (three cases) was consistent with a T-cell non-Hodgkin's lymphoma (large and small cells). Antibodies to HTLV-I were detected by ELISA and particle agglutination in the serum from eight of nine patients. DNA analysis showed HTLV-I proviral DNA in all seven cases investigated, including the single serologically negative patient. In five cases, HTLV-I was monoclonally integrated and in one case oligoclonal. In the seventh case viral DNA clonal status was ambiguous. Response to therapy was poor and median survival was 3 months (range 2-20 months). This study provides further evidence that HTLV-I is endemic in Chile, a non-tropical country where the two main diseases associated with HTLV-I, ATLL and TSP, are found.
Assuntos
Leucemia-Linfoma de Células T do Adulto/epidemiologia , Adulto , Idoso , Chile/epidemiologia , DNA Viral/análise , Saúde da Família , Feminino , Anticorpos Anti-HTLV-I/análise , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Imunofenotipagem , Leucemia-Linfoma de Células T do Adulto/imunologia , Leucemia-Linfoma de Células T do Adulto/virologia , Masculino , Pessoa de Meia-Idade , Provírus/genéticaRESUMO
We sequenced the envelope genes of Human T-cell leukemia type I viruses (HTLV-I) derived from five Brazilian, two Caribbean, and one Romanian case of adult T-cell leukemia after amplification of the complete env gene by PCR. A comparison with previously reported HTLV-I sequences revealed that, although highly homologous, no two env sequences were identical. All envelope sequences differed from each other by 0.3-2.1% nucleotide differences. The five Brazilian sequences clustered together and were about as different from each other (0.5-0.75% nucleotide difference) as were three previously reported Japanese sequences (0.7-0.95%). In contrast, sequences of Caribbean origin were less homogeneous (0.5-1.9% nucleotide differences within this group). The Romanian sequence was not significantly more divergent than any of the others and was closest to our two Caribbean sequences. We observed two changes in a region (aa 176-209) which has previously been shown to contain a linear antibody epitope recognized by most human sera from seropositive individuals. One of these changes affects the binding of monoclonal antibodies to this epitope demonstrating the variability of an antibody epitope in the HTLV-I envelope.