scholarly journals Seroreactivity to an Envelope Protein of Human T-Cell Leukemia/Lymphoma Virus in Patients With CD3− (Natural Killer) Lymphoproliferative Disease of Granular Lymphocytes

Blood ◽  
1997 ◽  
Vol 90 (5) ◽  
pp. 1977-1981 ◽  
Author(s):  
Thomas P. Loughran ◽  
Kenneth G. Hadlock ◽  
Qing Yang ◽  
Raisa Perzova ◽  
Renato Zambello ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Lymphoproliferative Disorder ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Htlv Infection ◽  
Human T Cell ◽  
Granular Lymphocytes

Abstract Natural killer (NK) cells are CD3− large granular lymphocytes (LGL) responsible for immunity against viral infections. A chronic lymphoproliferative disorder of NK cells has been described in which the expanded NK cells display a restricted phenotype and cytotoxic activity. These data raise the hypothesis that proliferating LGL in these patients result from discrete expansions of NK cells responding to an unknown, perhaps viral, antigen. Recently, it was found that mice transgenic for the tax gene of human T-cell leukemia/lymphoma virus (HTLV) develop NK leukemia. Therefore, we studied 15 patients with chronic NK lymphoproliferative disorder for evidence of HTLV infection. Sera were tested using an HTLV-I/II-enzyme linked immunosorbent assay and a modified Western blot assay containing recombinant env proteins. None of the sera met conventional criteria for HTLV seroreactivity. However, sera from 11 patients (73%) reacted with the recombinant HTLV env protein p21E. The anti-p21E reactivity of these sera was then mapped employing the recombinant proteins GD21 and BA21. No reactivity to the immunodominant HTLV epitope GD21 was observed, suggesting that prototypical HTLV infection is unlikely in these patients. This was confirmed by finding no evidence for HTLV nucleic acids by PCR analyses employing primers specific for conserved regions in the env, pol, and pX genes. In contrast, 10 of the 15 sera reacted with the epitope BA21, documenting for the first time an association between a unique seroreactivity and disease. The high incidence of BA21 seroreactivity in these patients suggests that exposure to a protein containing homology to BA21 may be important in the pathogenesis of this lymphoproliferative disorder.

scholarly journals Detection of human T-cell leukemia/lymphoma virus, type II, in a patient with large granular lymphocyte leukemia

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1116-1119 ◽  
Author(s):  
TP Jr Loughran ◽  
T Coyle ◽  
MP Sherman ◽  
G Starkebaum ◽  
GD Ehrlich ◽  
...  
Keyword(s):  
T Cell ◽  
Large Granular Lymphocyte ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Enzymatic Amplification ◽  
Htlv Infection ◽  
Human T Cell ◽  
Polymerase Chain ◽  
Lgl Leukemia

Abstract We studied a patient with large granular lymphocyte (LGL) leukemia for evidence of human T-cell leukemia/lymphoma virus (HTLV) infection. Serum from this patient was positive for HTLV-I/II antibodies by enzyme- linked immunosorbent assay (ELISA) and was confirmed positive in Western blot and radioimmunoprecipitation assays. Results of a synthetic peptide-based ELISA showed that the seropositivity was caused by HTLV-II and not HTLV-I infection. Analyses of enzymatic amplification of DNA from bone marrow sections using the polymerase chain reaction (PCR) were positive for HTLV-II specific gag, pol, env, and pX gene sequences. Cloning and sequencing of amplified products showed that the HTLV-II pol and pX sequences in patient DNA differed from the sequences of 17 other HTLV-II isolates examined in our laboratory. HTLV infection may have a role in some patients in the pathogenesis of LGL leukemia.

scholarly journals Successful Amplified-Natural-Killer Cell (ANK) Therapy Administered to a Patient with Smoldering Adult T-Cell Leukemia in Acute Crisis

Reports ◽  
2018 ◽  
Vol 1 (2) ◽  
pp. 13
Author(s):  
Keisuke Teshigawara ◽  
Sho Nagai ◽  
Gaowa Bai ◽  
Yuji Okubo ◽  
Haorile Chagan-Yasutan ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Killer Cell ◽  
Skin Tumor ◽  
Therapeutic Interventions ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Adult T-cell leukemia (ATL) is an indolent leukemia caused by type 1 human T-cell leukemia virus (HTLV-1). A variety of therapeutic interventions via immunological approaches have been attempted. ATL cells express costimulatory molecules of natural killer (NK) cells, and a new modality—amplified NK (ANK) cell treatment—was administered here to a patient with ATL. A 70-year-old female presenting with ringworm infection received a diagnosis of smoldering ATL in 2004. Monitoring of soluble IL-2 receptors (sIL-2Rs) in the serum showed disease exacerbation in 2007, associated with the enlargement of lymph nodes and formation of a skin tumor. NK cells were amplified by in vitro cell culture methods. To avoid cytokine release syndrome, 2–5 × 108 cells were administered with each injection. A total of 15 injections from 12 November 2007 to 15 February 2008 were administered to this patient. This case showed drastic downregulation of sIL-2R, resulting in the induction of complete remission, which lasted for >5 years. This is the first report of treatment of a patient with ATL using ANK cell therapy. More attempts of this therapy will enhance our insight into the appropriate application of this new therapy to clinically diverse patients.

scholarly journals Detection of human T-cell leukemia/lymphoma virus, type II, in a patient with large granular lymphocyte leukemia

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1116-1119 ◽  
Author(s):  
TP Jr Loughran ◽  
T Coyle ◽  
MP Sherman ◽  
G Starkebaum ◽  
GD Ehrlich ◽  
...  
Keyword(s):  
T Cell ◽  
Large Granular Lymphocyte ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Enzymatic Amplification ◽  
Htlv Infection ◽  
Human T Cell ◽  
Polymerase Chain ◽  
Lgl Leukemia

We studied a patient with large granular lymphocyte (LGL) leukemia for evidence of human T-cell leukemia/lymphoma virus (HTLV) infection. Serum from this patient was positive for HTLV-I/II antibodies by enzyme- linked immunosorbent assay (ELISA) and was confirmed positive in Western blot and radioimmunoprecipitation assays. Results of a synthetic peptide-based ELISA showed that the seropositivity was caused by HTLV-II and not HTLV-I infection. Analyses of enzymatic amplification of DNA from bone marrow sections using the polymerase chain reaction (PCR) were positive for HTLV-II specific gag, pol, env, and pX gene sequences. Cloning and sequencing of amplified products showed that the HTLV-II pol and pX sequences in patient DNA differed from the sequences of 17 other HTLV-II isolates examined in our laboratory. HTLV infection may have a role in some patients in the pathogenesis of LGL leukemia.

scholarly journals Unusual pattern of antibodies to human T-cell leukemia virus type-I in family members of adult T-cell leukemia patients

Blood ◽  
1991 ◽  
Vol 78 (12) ◽  
pp. 3323-3329
Author(s):  
A Okayama ◽  
B Korber ◽  
YM Chen ◽  
J Allan ◽  
TH Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Htlv Infection ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Detection methods for the human T-cell leukemia virus type-I (HTLV-I) for blood screening and diagnosis generally rely on antibody tests that use the structural proteins of HTLV-I as antigen. We have found an unusual pattern of antibody reactivity among people who are at high risk of HTLV infection due to being a family member of an adult T-cell leukemia (ATL) patient: a specific antibody reaction exclusively directed to the HTLV regulatory protein tax, and not to the HTLV-I structural proteins. Sera from 7 of 82 (8.5%) structural antibody- undetectable family members of ATL patients had the anti-tax reactivity. Two seroconverters were observed. One seroconverter a healthy resident of Miyazaki, tested negative for structural antibody, but positive for tax antibody. Two years later she tested positive for both. The other seroconverter, an Israeli hemophiliac, tested negative for both antibodies, but converted to tax antibody-positive/structural antibody-negative. The HTLV-I tax-only antibody profile was also observed in sera sets from two other populations at risk for HTLV infection, human immunodeficiency virus-1-infected patients at the Bronx-Lebanon Hospital in New York and Israeli hemophiliacs. DNA samples from lymphocytes of four individuals with antibody reactivity only to HTLV-I tax were tested in polymerase chain reaction experiments; no HTLV-I or -II DNA was detected.

scholarly journals Potential role of natural killer cells in controlling tumorigenesis by human T-cell leukemia viruses.

1995 ◽  
Vol 69 (2) ◽  
pp. 1328-1333 ◽  
Author(s):  
G Feuer ◽  
S A Stewart ◽  
S M Baird ◽  
F Lee ◽  
R Feuer ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Potential Role ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Killer Cells ◽  
Human T Cell ◽  
Leukemia Viruses

scholarly journals Soluble interleukin 2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 1021-1026 ◽  
Author(s):  
N Yasuda ◽  
PK Lai ◽  
SH Ip ◽  
PC Kung ◽  
Y Hinuma ◽  
...  
Keyword(s):  
T Cell ◽  
Interleukin 2 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Normal Range ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Abstract Serum concentrations of soluble interleukin 2 receptors (sIL 2R) were measured by an enzyme-linked immunosorbent assay (ELISA) in 30 patients with adult T cell leukemia (ATL), in 9 patients with other hematopoietic malignancies, and in 17 asymptomatic individuals seropositive for human T cell leukemia virus type I (HTLV-I). Sixty HTLV-I seronegative, age-matched controls showed a normal range of form 63.2 to 480.8 U/mL. All asymptomatic carriers of HTLV-I had sIL 2R in their sera within the normal range. sIL 2R in sera was not related to the anti-HTLV-I antibody titer. Eleven patients with acute ATL, a clinical phenotype with median survival rate of 4.4 months, had markedly elevated sIL 2R (11,100 to 99,000 U/mL), but eight patients with smoldering ATL had low sIL 2R values (less than 480.8 U/mL) comparable to controls. Eleven patients with chronic ATL had intermediate elevated levels of sIL 2R (480.8 to 37,300.0 U/mL). Serum levels of sIL 2R correlated with the number of ATL cells (r = 0.812) and CD25-positive cells (r = 0.725) circulating in the peripheral blood. Longitudinal studies performed in four patients with ATL showed significant correlation between serum concentration of sIL 2R and activity of the malignancy. These findings suggest that the level of sIL 2R in serum indicated tumor load and, possibly, prognosis.

scholarly journals Evidence of New Endemic Clusters of Human T-Cell Leukemia Virus (HTLV) Infection in Bahia, Brazil

2019 ◽  
Vol 10 ◽  
Author(s):  
Felicidade Mota Pereira ◽  
Maria da Conceição Chagas de Almeida ◽  
Fred Luciano Neves Santos ◽  
Roberto Perez Carreiro ◽  
Carlos Gustavo Regis-Silva ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Htlv Infection ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL

2020 ◽  
Vol 4 (6) ◽  
pp. 1062-1071
Author(s):  
Carmina Louise Hugo Guerrero ◽  
Yoshiko Yamashita ◽  
Megumi Miyara ◽  
Naoki Imaizumi ◽  
Megumi Kato ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Cell Leukemia ◽  
Proteomic Profiling ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell

Abstract Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type 1 (HTLV-1)–associated T-cell malignancy with generally poor prognosis. Although only ∼5% of HTLV-1 carriers progress to ATL, early diagnosis is challenging because of the lack of ATL biomarkers. In this study, we analyzed blood plasma profiles of asymptomatic HTLV-1 carriers (ACs); untreated ATL patients, including acute, lymphoma, smoldering, and chronic types; and ATL patients in remission. Through SOMAscan, expression levels of 1305 plasma proteins were analyzed in 85 samples (AC, n = 40; ATL, n = 40; remission, n = 5). Using gene set enrichment analysis and gene ontology, overrepresented pathways in ATL vs AC included angiogenesis, inflammation by cytokines and chemokines, interleukin-6 (IL-6)/JAK/STAT3, and notch signaling. In selecting candidate biomarkers, we focused on soluble tumor necrosis factor receptor 2 (sTNFR2) because of its active role in enriched pathways, extreme significance (Welch’s t test P < .00001), high discrimination capacity (area under the curve >0.90), and novelty in ATL research. Quantification of sTNFR2 in 102 plasma samples (AC, n = 30; ATL, n = 68; remission, n = 4) using enzyme-linked immunosorbent assay showed remarkable elevations in acute ATL, at least 10 times those of AC samples, and return of sTNFR2 to AC state levels after achieving remission. Flow cytometry and immunostaining validated the expression of TNFR2 in ATL cells. No correlation between sIL-2 and sTNFR2 levels in acute ATL was found, suggesting the possibility of sTNFR2 as an independent biomarker. Our findings represent the first extensive blood-based proteomic analysis of ATL, suggesting the potential clinical utility of sTNFR2 in diagnosing acute ATL.

scholarly journals Soluble interleukin 2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 1021-1026 ◽  
Author(s):  
N Yasuda ◽  
PK Lai ◽  
SH Ip ◽  
PC Kung ◽  
Y Hinuma ◽  
...  
Keyword(s):  
T Cell ◽  
Interleukin 2 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Normal Range ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Serum concentrations of soluble interleukin 2 receptors (sIL 2R) were measured by an enzyme-linked immunosorbent assay (ELISA) in 30 patients with adult T cell leukemia (ATL), in 9 patients with other hematopoietic malignancies, and in 17 asymptomatic individuals seropositive for human T cell leukemia virus type I (HTLV-I). Sixty HTLV-I seronegative, age-matched controls showed a normal range of form 63.2 to 480.8 U/mL. All asymptomatic carriers of HTLV-I had sIL 2R in their sera within the normal range. sIL 2R in sera was not related to the anti-HTLV-I antibody titer. Eleven patients with acute ATL, a clinical phenotype with median survival rate of 4.4 months, had markedly elevated sIL 2R (11,100 to 99,000 U/mL), but eight patients with smoldering ATL had low sIL 2R values (less than 480.8 U/mL) comparable to controls. Eleven patients with chronic ATL had intermediate elevated levels of sIL 2R (480.8 to 37,300.0 U/mL). Serum levels of sIL 2R correlated with the number of ATL cells (r = 0.812) and CD25-positive cells (r = 0.725) circulating in the peripheral blood. Longitudinal studies performed in four patients with ATL showed significant correlation between serum concentration of sIL 2R and activity of the malignancy. These findings suggest that the level of sIL 2R in serum indicated tumor load and, possibly, prognosis.

scholarly journals Unusual pattern of antibodies to human T-cell leukemia virus type-I in family members of adult T-cell leukemia patients

Blood ◽  
1991 ◽  
Vol 78 (12) ◽  
pp. 3323-3329 ◽  
Author(s):  
A Okayama ◽  
B Korber ◽  
YM Chen ◽  
J Allan ◽  
TH Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Htlv Infection ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Abstract Detection methods for the human T-cell leukemia virus type-I (HTLV-I) for blood screening and diagnosis generally rely on antibody tests that use the structural proteins of HTLV-I as antigen. We have found an unusual pattern of antibody reactivity among people who are at high risk of HTLV infection due to being a family member of an adult T-cell leukemia (ATL) patient: a specific antibody reaction exclusively directed to the HTLV regulatory protein tax, and not to the HTLV-I structural proteins. Sera from 7 of 82 (8.5%) structural antibody- undetectable family members of ATL patients had the anti-tax reactivity. Two seroconverters were observed. One seroconverter a healthy resident of Miyazaki, tested negative for structural antibody, but positive for tax antibody. Two years later she tested positive for both. The other seroconverter, an Israeli hemophiliac, tested negative for both antibodies, but converted to tax antibody-positive/structural antibody-negative. The HTLV-I tax-only antibody profile was also observed in sera sets from two other populations at risk for HTLV infection, human immunodeficiency virus-1-infected patients at the Bronx-Lebanon Hospital in New York and Israeli hemophiliacs. DNA samples from lymphocytes of four individuals with antibody reactivity only to HTLV-I tax were tested in polymerase chain reaction experiments; no HTLV-I or -II DNA was detected.

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