Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

Peter D. Burbelo, Elise Meoli, Hannah P. Leahy, Jhanelle Graham, Karen Yao, Unsong Oh, John Edward Janik, Renaud Mahieux, Fatah Kashanchi, Michael J. Iadarola, Steven Jacobson

Research output: Contribution to journalArticle

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Abstract

Background: HTLV-I is the causal agent of adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Biomarkers are needed to diagnose and/or predict patients who are at risk for HAM/TSP or ATLL. Therefore, we investigated using luciferase immunoprecipitation technology (LIPS) antibody responses to seven HTLV-I proteins in non-infected controls, asymptomatic HTLV-I-carriers, ATLL and HAM/TSP sera samples. Antibody profiles were correlated with viral load and examined in longitudinal samples. Results: Anti-GAG antibody titers detected by LIPS differentiated HTLV-infected subjects from uninfected controls with 100% sensitivity and 100% specificity, but did not differ between HTLV-I infected subgroups. However, anti-Env antibody titers were over 4-fold higher in HAM/TSP compared to both asymptomatic HTLV-I (P < 0.0001) and ATLL patients (P < 0.0005). Anti-Env antibody titers above 100,000 LU had 75% positive predictive value and 79% negative predictive value for identifying the HAM/TSP sub-type. Anti-Tax antibody titers were also higher (P < 0.0005) in the HAM/TSP compared to the asymptomatic HTLV-I carriers. Proviral load correlated with anti-Env antibodies in asymptomatic carriers (R = 0.76), but not in HAM/TSP. Conclusion: These studies indicate that anti-HTLV-I antibody responses detected by LIPS are useful for diagnosis and suggest that elevated anti-Env antibodies are a common feature found in HAM/TSP patients.

Original languageEnglish (US)
Article number96
JournalRetrovirology
Volume5
DOIs
StatePublished - Oct 20 2008

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Deltaretrovirus Antibodies
Tropical Spastic Paraparesis
Human T-lymphotropic virus 1
Anti-Idiotypic Antibodies
Adult T Cell Leukemia Lymphoma
Antibodies
Antibody Formation
HTLV-I Antibodies
Viral Load
Luciferases
Immunoprecipitation
Biomarkers
Technology

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). / Burbelo, Peter D.; Meoli, Elise; Leahy, Hannah P.; Graham, Jhanelle; Yao, Karen; Oh, Unsong; Janik, John Edward; Mahieux, Renaud; Kashanchi, Fatah; Iadarola, Michael J.; Jacobson, Steven.

In: Retrovirology, Vol. 5, 96, 20.10.2008.

Research output: Contribution to journalArticle

Burbelo, PD, Meoli, E, Leahy, HP, Graham, J, Yao, K, Oh, U, Janik, JE, Mahieux, R, Kashanchi, F, Iadarola, MJ & Jacobson, S 2008, 'Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)', Retrovirology, vol. 5, 96. https://doi.org/10.1186/1742-4690-5-96
Burbelo, Peter D. ; Meoli, Elise ; Leahy, Hannah P. ; Graham, Jhanelle ; Yao, Karen ; Oh, Unsong ; Janik, John Edward ; Mahieux, Renaud ; Kashanchi, Fatah ; Iadarola, Michael J. ; Jacobson, Steven. / Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In: Retrovirology. 2008 ; Vol. 5.
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abstract = "Background: HTLV-I is the causal agent of adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Biomarkers are needed to diagnose and/or predict patients who are at risk for HAM/TSP or ATLL. Therefore, we investigated using luciferase immunoprecipitation technology (LIPS) antibody responses to seven HTLV-I proteins in non-infected controls, asymptomatic HTLV-I-carriers, ATLL and HAM/TSP sera samples. Antibody profiles were correlated with viral load and examined in longitudinal samples. Results: Anti-GAG antibody titers detected by LIPS differentiated HTLV-infected subjects from uninfected controls with 100{\%} sensitivity and 100{\%} specificity, but did not differ between HTLV-I infected subgroups. However, anti-Env antibody titers were over 4-fold higher in HAM/TSP compared to both asymptomatic HTLV-I (P < 0.0001) and ATLL patients (P < 0.0005). Anti-Env antibody titers above 100,000 LU had 75{\%} positive predictive value and 79{\%} negative predictive value for identifying the HAM/TSP sub-type. Anti-Tax antibody titers were also higher (P < 0.0005) in the HAM/TSP compared to the asymptomatic HTLV-I carriers. Proviral load correlated with anti-Env antibodies in asymptomatic carriers (R = 0.76), but not in HAM/TSP. Conclusion: These studies indicate that anti-HTLV-I antibody responses detected by LIPS are useful for diagnosis and suggest that elevated anti-Env antibodies are a common feature found in HAM/TSP patients.",
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T1 - Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

AU - Burbelo, Peter D.

AU - Meoli, Elise

AU - Leahy, Hannah P.

AU - Graham, Jhanelle

AU - Yao, Karen

AU - Oh, Unsong

AU - Janik, John Edward

AU - Mahieux, Renaud

AU - Kashanchi, Fatah

AU - Iadarola, Michael J.

AU - Jacobson, Steven

PY - 2008/10/20

Y1 - 2008/10/20

N2 - Background: HTLV-I is the causal agent of adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Biomarkers are needed to diagnose and/or predict patients who are at risk for HAM/TSP or ATLL. Therefore, we investigated using luciferase immunoprecipitation technology (LIPS) antibody responses to seven HTLV-I proteins in non-infected controls, asymptomatic HTLV-I-carriers, ATLL and HAM/TSP sera samples. Antibody profiles were correlated with viral load and examined in longitudinal samples. Results: Anti-GAG antibody titers detected by LIPS differentiated HTLV-infected subjects from uninfected controls with 100% sensitivity and 100% specificity, but did not differ between HTLV-I infected subgroups. However, anti-Env antibody titers were over 4-fold higher in HAM/TSP compared to both asymptomatic HTLV-I (P < 0.0001) and ATLL patients (P < 0.0005). Anti-Env antibody titers above 100,000 LU had 75% positive predictive value and 79% negative predictive value for identifying the HAM/TSP sub-type. Anti-Tax antibody titers were also higher (P < 0.0005) in the HAM/TSP compared to the asymptomatic HTLV-I carriers. Proviral load correlated with anti-Env antibodies in asymptomatic carriers (R = 0.76), but not in HAM/TSP. Conclusion: These studies indicate that anti-HTLV-I antibody responses detected by LIPS are useful for diagnosis and suggest that elevated anti-Env antibodies are a common feature found in HAM/TSP patients.

AB - Background: HTLV-I is the causal agent of adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Biomarkers are needed to diagnose and/or predict patients who are at risk for HAM/TSP or ATLL. Therefore, we investigated using luciferase immunoprecipitation technology (LIPS) antibody responses to seven HTLV-I proteins in non-infected controls, asymptomatic HTLV-I-carriers, ATLL and HAM/TSP sera samples. Antibody profiles were correlated with viral load and examined in longitudinal samples. Results: Anti-GAG antibody titers detected by LIPS differentiated HTLV-infected subjects from uninfected controls with 100% sensitivity and 100% specificity, but did not differ between HTLV-I infected subgroups. However, anti-Env antibody titers were over 4-fold higher in HAM/TSP compared to both asymptomatic HTLV-I (P < 0.0001) and ATLL patients (P < 0.0005). Anti-Env antibody titers above 100,000 LU had 75% positive predictive value and 79% negative predictive value for identifying the HAM/TSP sub-type. Anti-Tax antibody titers were also higher (P < 0.0005) in the HAM/TSP compared to the asymptomatic HTLV-I carriers. Proviral load correlated with anti-Env antibodies in asymptomatic carriers (R = 0.76), but not in HAM/TSP. Conclusion: These studies indicate that anti-HTLV-I antibody responses detected by LIPS are useful for diagnosis and suggest that elevated anti-Env antibodies are a common feature found in HAM/TSP patients.

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