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Humoral immune response to HTLV-1 basic leucine zipper factor (HBZ) in HTLV-1-infected individuals.

Enose-Akahata Y, Abrams A, Massoud R, Bialuk I, Johnson KR, Green PL, Maloney EM, Jacobson S - Retrovirology (2013)

Bottom Line: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP.This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection.Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

ABSTRACT

Background: Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1-infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system.

Results: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4+ T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients.

Conclusions: This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.

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Related in: MedlinePlus

Antibody responses against HBZ from serum/plasma of ND, AC, ATL patients and HAM/TSP patients. (A) Comparison of antibody responses against HBZ in serum/plasma of ND, AC, ATL and HAM/TSP patients using Mann–Whitney Test. The data were obtained from 98 ND, 145 AC, 89 ATL patients and 104 HAM/TSP patients. Antibody responses against HBZ were detected in HTLV-1-infected groups (AC, ATL and HAM/TSP). The horizontal line represents the mean. Dotted line represents cut-off value (6853LU). (B) Frequency of subjects with antibody response against HBZ in serum/plasma of ND, AC, ATL and HAM/TSP patients. The distribution of subjects with antibody response against HBZ among the groups was compared by Chi-Square Test. (C) Comparison of antibody responses against HBZ in serum of ATL patients by ATL subtypes using Mann–Whitney Test. The data were obtained from 30 acute, 29 chronic and 30 lymphoma ATL patients. The horizontal line represents the mean. Dotted line represents cut-off value (6853LU). (D) Frequency of subjects with antibody response against HBZ in serum of ATL patients. The distribution of subjects with antibody response against HBZ among the groups was compared by Chi-Square Test.
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Figure 1: Antibody responses against HBZ from serum/plasma of ND, AC, ATL patients and HAM/TSP patients. (A) Comparison of antibody responses against HBZ in serum/plasma of ND, AC, ATL and HAM/TSP patients using Mann–Whitney Test. The data were obtained from 98 ND, 145 AC, 89 ATL patients and 104 HAM/TSP patients. Antibody responses against HBZ were detected in HTLV-1-infected groups (AC, ATL and HAM/TSP). The horizontal line represents the mean. Dotted line represents cut-off value (6853LU). (B) Frequency of subjects with antibody response against HBZ in serum/plasma of ND, AC, ATL and HAM/TSP patients. The distribution of subjects with antibody response against HBZ among the groups was compared by Chi-Square Test. (C) Comparison of antibody responses against HBZ in serum of ATL patients by ATL subtypes using Mann–Whitney Test. The data were obtained from 30 acute, 29 chronic and 30 lymphoma ATL patients. The horizontal line represents the mean. Dotted line represents cut-off value (6853LU). (D) Frequency of subjects with antibody response against HBZ in serum of ATL patients. The distribution of subjects with antibody response against HBZ among the groups was compared by Chi-Square Test.

Mentions: Antibody responses for HBZ were analyzed in the separate groups of Jamaican and NIH subjects. There were no significant differences in frequency or magnitude of anti-HBZ antibody responses in serum/plasma between Jamaican and NIH subjects (data not shown) so they were combined in the remaining analyses, yielding a total of 436 serum/plasma samples obtained from ND, AC, ATL patients and HAM/TSP patients. Strong mean antibody levels against HBZ were detected in the HTLV-1-infected groups, including AC, ATL patients and HAM/TSP patients, compared to the ND group (Figure 1A and Table 2). Although the mean antibody level against HBZ among the ATL subjects did not differ significantly from those of the ND group, the differences of the mean antibody level were statistically significant for the AC and HAM/TSP groups relative to the ND group (Figure 1A). Within each HTLV-1-infected group, robust anti-HBZ antibody responses (209751.9-1180625.0 LU) were observed in subsets of individuals, but among the HTLV-1-infected groups, the mean anti-HBZ antibody levels were not significantly different (Figure 1A). When the data were analyzed as the percent of positive responders above a negative threshold (6853 LU; dotted line in Figure 1A), immunoreactivity against HBZ was detected in 10.34% (15/145) of AC, 12.36% (11/89) of ATL patients, and 13.46% (14/104) of HAM/TSP patients (Figure 1B and Table 2). The frequency of immunoreactivity in each of the HTLV-1-infected groups was significantly higher than the ND group, but again there were no statistically significant differences between the HTLV-1-infected groups (Figure 1B). In addition, the Four-Way Analysis of Variance (ANOVA) model with interactions using race, gender, age and study group as factors showed no significant differences of the level of immunoreactivity against HBZ by gender, race and age between each study group (data not shown). There were also no significant differences in the frequency of immunoreactivity against HBZ by gender, race and age between each study group (data not shown).


Humoral immune response to HTLV-1 basic leucine zipper factor (HBZ) in HTLV-1-infected individuals.

Enose-Akahata Y, Abrams A, Massoud R, Bialuk I, Johnson KR, Green PL, Maloney EM, Jacobson S - Retrovirology (2013)

Antibody responses against HBZ from serum/plasma of ND, AC, ATL patients and HAM/TSP patients. (A) Comparison of antibody responses against HBZ in serum/plasma of ND, AC, ATL and HAM/TSP patients using Mann–Whitney Test. The data were obtained from 98 ND, 145 AC, 89 ATL patients and 104 HAM/TSP patients. Antibody responses against HBZ were detected in HTLV-1-infected groups (AC, ATL and HAM/TSP). The horizontal line represents the mean. Dotted line represents cut-off value (6853LU). (B) Frequency of subjects with antibody response against HBZ in serum/plasma of ND, AC, ATL and HAM/TSP patients. The distribution of subjects with antibody response against HBZ among the groups was compared by Chi-Square Test. (C) Comparison of antibody responses against HBZ in serum of ATL patients by ATL subtypes using Mann–Whitney Test. The data were obtained from 30 acute, 29 chronic and 30 lymphoma ATL patients. The horizontal line represents the mean. Dotted line represents cut-off value (6853LU). (D) Frequency of subjects with antibody response against HBZ in serum of ATL patients. The distribution of subjects with antibody response against HBZ among the groups was compared by Chi-Square Test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3584941&req=5

Figure 1: Antibody responses against HBZ from serum/plasma of ND, AC, ATL patients and HAM/TSP patients. (A) Comparison of antibody responses against HBZ in serum/plasma of ND, AC, ATL and HAM/TSP patients using Mann–Whitney Test. The data were obtained from 98 ND, 145 AC, 89 ATL patients and 104 HAM/TSP patients. Antibody responses against HBZ were detected in HTLV-1-infected groups (AC, ATL and HAM/TSP). The horizontal line represents the mean. Dotted line represents cut-off value (6853LU). (B) Frequency of subjects with antibody response against HBZ in serum/plasma of ND, AC, ATL and HAM/TSP patients. The distribution of subjects with antibody response against HBZ among the groups was compared by Chi-Square Test. (C) Comparison of antibody responses against HBZ in serum of ATL patients by ATL subtypes using Mann–Whitney Test. The data were obtained from 30 acute, 29 chronic and 30 lymphoma ATL patients. The horizontal line represents the mean. Dotted line represents cut-off value (6853LU). (D) Frequency of subjects with antibody response against HBZ in serum of ATL patients. The distribution of subjects with antibody response against HBZ among the groups was compared by Chi-Square Test.
Mentions: Antibody responses for HBZ were analyzed in the separate groups of Jamaican and NIH subjects. There were no significant differences in frequency or magnitude of anti-HBZ antibody responses in serum/plasma between Jamaican and NIH subjects (data not shown) so they were combined in the remaining analyses, yielding a total of 436 serum/plasma samples obtained from ND, AC, ATL patients and HAM/TSP patients. Strong mean antibody levels against HBZ were detected in the HTLV-1-infected groups, including AC, ATL patients and HAM/TSP patients, compared to the ND group (Figure 1A and Table 2). Although the mean antibody level against HBZ among the ATL subjects did not differ significantly from those of the ND group, the differences of the mean antibody level were statistically significant for the AC and HAM/TSP groups relative to the ND group (Figure 1A). Within each HTLV-1-infected group, robust anti-HBZ antibody responses (209751.9-1180625.0 LU) were observed in subsets of individuals, but among the HTLV-1-infected groups, the mean anti-HBZ antibody levels were not significantly different (Figure 1A). When the data were analyzed as the percent of positive responders above a negative threshold (6853 LU; dotted line in Figure 1A), immunoreactivity against HBZ was detected in 10.34% (15/145) of AC, 12.36% (11/89) of ATL patients, and 13.46% (14/104) of HAM/TSP patients (Figure 1B and Table 2). The frequency of immunoreactivity in each of the HTLV-1-infected groups was significantly higher than the ND group, but again there were no statistically significant differences between the HTLV-1-infected groups (Figure 1B). In addition, the Four-Way Analysis of Variance (ANOVA) model with interactions using race, gender, age and study group as factors showed no significant differences of the level of immunoreactivity against HBZ by gender, race and age between each study group (data not shown). There were also no significant differences in the frequency of immunoreactivity against HBZ by gender, race and age between each study group (data not shown).

Bottom Line: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP.This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection.Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

ABSTRACT

Background: Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1-infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system.

Results: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4+ T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients.

Conclusions: This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.

Show MeSH
Related in: MedlinePlus