Clinical significance of serum soluble IL-2R levels in patients with adult T cell leukaemia (ATL) and HTLV-1 carriers

Araki,; Harada$^{, }$; Nakamoto,; Shiroma,; Miyakuni,

doi:10.1046/j.1365-2249.2000.01136.x

Cited by 18 publications

(13 citation statements)

References 23 publications

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“…However, a high titer of the antibody was later detected, in the third sample taken 15 days before a relapse, as was an increase in the serum sIL‐2R level, a hallmark of ATL. ( 19,20 ) In contrast, in the case of patients P004, P005 and P006, seroconversion of anti‐gp46–197 antibody was observed. In P004, the antibody was not detected in the chronic state, but seroconversion was observed along with the progression to acute ATL (crisis).…”

Section: Resultsmentioning

confidence: 92%

Antibody to the central region of human T‐lymphotropic virus type 1 gp46 is associated with the progression of adult T‐cell leukemia

et al. 2006

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Human T-cell lymphotropic virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia/lymphoma (ATL). HTLV-1 is spread by cellto-cell transmission via the gp46-197 region, Asp197 to Leu216, on the envelope protein gp46. In the present study, we revealed a positive correlation between the appearance of an antibody recognizing the gp46-197 region (anti-gp46-197 antibody) and the severity of ATL. The prevalence and titer of the anti-gp46-197 antibody were found to be elevated along with the progression of ATL. In serial samples obtained from a single patient, the anti-gp46-197 antibody was detected before treatment in acute phase, then diminished after allogeneic bone marrow transplantation, to which the patient had a complete response. However, the antibody appeared again before a relapse, along with an increase of the serum-soluble interleukin-2 receptor level and proviral load. The results from the other six patients also indicate that seroconversion of this antibody was synchronized with the deterioration of ATL. Taken (1,2) ATL is characterized by tumor cells with mature T-lymphocyte phenotypes, onset in middle-aged or elderly individuals infected with HTLV-1 through breast milk, and by the presence of leukemic cells with multilobulated nuclei bearing chromosomal abnormalities. It has been observed that the HTLV-1 provirus integrates randomly into the human genome in asymptomatic carriers (AC), resulting in only a smear pattern of proviral DNA by Southern blot analysis. However, monoclonal integration bands detected by Southern blot analysis indicate clonal proliferation of neoplastic leukemia/ lymphoma cells infected with HTLV-1. Patients with ATL are classified into four clinical subtypes based on Shimoyama's diagnostic criteria: acute, lymphoma, chronic and smoldering. Patients with chronic and smoldering ATL are in a basically healthy state, but often progress to acute ATL after a long incubation. In lymphoma-type ATL, few abnormal cells are observed in peripheral white blood cells, but patients die in the short course, as in the acute type. Recently, therapeutic trials of allogeneic hematopoietic stem cell transplantation for ATL treatment have been reported, with such treatment leading some ATL patients to long-lasting complete remission with no detection of HTLV-1 provirus, (4) but the overall prognosis continues to be poor. There is no evidence of virus in plasma in vivo or HTLV-1 infection as a result of blood transfusion in patients who received only plasma products from seropositive blood donors. (5) Thus, it is apparent that HTLV-1 transmission occurs via cell-cell contact and is inefficient by cell-free body fluids. Previously, we demonstrated that the gp46 -197 region, corresponding to the region from Asp197 to Leu216 on envelope protein gp46 of HTLV-1, functions as a receptor binding site in cell-to-cell infection of HTLV-1.(6) The 71-kDa heat shock cognate protein (HSC70) acts as an HTLV-1 receptor on the cell surface by binding to the gp46 -197 region. (7,8) Recently, it was reported...

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Section: Resultsmentioning

confidence: 92%

Antibody to the central region of human T‐lymphotropic virus type 1 gp46 is associated with the progression of adult T‐cell leukemia

et al. 2006

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“…In addi- VCA, viral capsid antigen; EA, early antigen; CRP, C-reactive protein; sIL2R, soluble IL-2 receptor-a; sCD30, soluble CD30; IgE, immunoglobulin E. 1 Reciprocal of the geometric mean titer, or geometric mean level, from mixed-effects linear regression analyses adjusted for age (continuous, in years), sex and year of sample collection (continuous); p-values were obtained from the t-test and reflect covariate adjustment.-2 pvalues were obtained from the Mantel-Haenszel test, adjusted for age (<60 vs. 601 yr), sex and year of sample collection (1987-1989 vs. 1990-1993).-3 A low EBNA1:EBNA2 ratio is a ratio of anti-EBNA1 to anti-EBNA2 titers 1.0.-4 Values below assay detection level are assigned a value of one-half the assay detection limit and included in the estimation of the geometric mean. tion, elevated plasma sIL2R 38,39 and sCD30 levels 40,41 have been reported in ATL patients and likely reflect tumor burden related to IL2R and CD30 expression by ATL cells. 25,26 HAM/TSP patients and asymptomatic HTLV-I carriers were also reported to have significantly higher sIL2R levels than noncarriers in a predominantly Caribbean population.…”

Section: Discussionmentioning

confidence: 92%

“…In addition, elevated plasma sIL2R (38,39) and sCD30 levels (40,41) have been reported in ATL patients and likely reflect tumor burden related to IL2R and CD30 expression by ATL cells (25,26). HAM/TSP patients and asymptomatic HTLV-I carriers were also reported to have significantly higher sIL2R levels than non-carriers in a predominantly Caribbean population (42).…”

Section: Discussionmentioning

confidence: 99%

Population differences in immune marker profiles associated with human T‐lymphotropic virus type I infection in Japan and Jamaica

Birmann

Breen

Stuver

et al. 2008

Intl Journal of Cancer

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The natural history of human T‐lymphotropic virus type I (HTLV‐I) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T‐cell lymphoma (ATL) and HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV‐I‐endemic populations in Japan and Jamaica. We matched 204 participants with archived blood from the Miyazaki Cohort Study (Japan) and the Food Handlers Study (Jamaica)—i.e., 51 HTLV‐I‐positive (“carriers”) and 51 HTLV‐I‐negative individuals (“noncarriers”) from each population—by age, sex and blood collection year. We compared plasma concentrations of markers of T‐cell‐mediated (antigen‐specific) and nonspecific immunity using regression models and correlation coefficients. Compared to Jamaican HTLV‐I noncarriers, Japanese noncarriers had higher covariate‐adjusted mean levels of T‐cell activation markers, including antibody to Epstein‐Barr virus nuclear antigen‐1 (reciprocal titer 27 vs. 71, respectively, p = 0.005), soluble interleukin‐2 receptor‐α (477 vs. 623 pg/mL, p = 0.0008) and soluble CD30 (34 vs. 46 U/mL, p = 0.0001) and lower levels of C‐reactive protein (1.1 vs. 0.43 μg/mL, p = 0.0004). HTLV‐I infection was associated with activated T‐cell immunity in Jamaicans but with diminished T‐cell immunity in Japanese persons. The observed population differences in background and HTLV‐I‐related host immunity correspond closely to the divergent natural histories of infection observed among HTLV‐I carriers in Japan and Jamaica and corroborate a role for host immune status in the contrasting patterns of ATL and HAM/TSP risk. © 2008 Wiley‐Liss, Inc.

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“…The mean serum levels of the soluble IL‐2 receptor in the chronic and smouldering phase were 1961 U/mL and 788 U/mL, respectively. In contrast, in HTLV‐1 carriers the level was 475 U/mL (56). Patients with the smouldering form are usually asymptomatic, and the diagnosis is based on the presence of 5% or more atypical lymphocytes with the total lymphocyte count lower than 4000 cells/mm 3 .…”

Section: Clinical Features Of Strongyloidiasis and Htlv‐1 Infectionmentioning

confidence: 99%

Epidemiological and clinical interaction between HTLV‐1 and Strongyloides stercoralis

Carvalho

Porto

2004

Parasite Immunology

204

169

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Strongyloides stercoralis is the most common human parasitic nematode that is able to complete a life cycle and proliferate within its host. The majority of patients with strongyloidiasis have an asymptomatic infection or mild disease. However, when autoinfection occurs, a high number of infecting larvae can gain access to the bloodstream by penetrating the colonic mucosa leading to a severe hyperinfection and the development of disseminated strongyloidiasis. The human T cell lymphotropic virus type 1 (HTLV-1) predominantly infects T cells and induces spontaneous lymphocyte proliferation and secretion of high levels of type 1 cytokines. Strongyloides stercoralis patients with HTLV-1 co-infection have a modified immunological responses against parasite antigens and co-infection has clinical implications for strongyloidiasis. The high production of IFN-gamma observed in patients co-infected with HTLV-1 and Strongyloides stercoralis decreases the production of IL-4, IL-5, IL-13 and IgE, molecules that participate in the host defence mechanism against helminths. Moreover, there is a decrease in the efficacy of treatment of Strongyloides stercoralis in patients co-infected with HTLV-1. Alterations in the immune response against Strongyloides stercoralis and the decrease in the efficacy of anti-parasitic drugs are responsible for the increased prevalence of Strongyloides stercoralis among HTLV-1 infected subjects and make HTLV-1 infection the most important risk factor for disseminated strongyloidiasis.

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Clinical significance of serum soluble IL-2R levels in patients with adult T cell leukaemia (ATL) and HTLV-1 carriers

Cited by 18 publications

References 23 publications

Antibody to the central region of human T‐lymphotropic virus type 1 gp46 is associated with the progression of adult T‐cell leukemia

Antibody to the central region of human T‐lymphotropic virus type 1 gp46 is associated with the progression of adult T‐cell leukemia

Population differences in immune marker profiles associated with human T‐lymphotropic virus type I infection in Japan and Jamaica

Epidemiological and clinical interaction between HTLV‐1 and Strongyloides stercoralis

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