Detection of HCV-specific IFN-gamma responses in HCV antibody and HCV RNA negative injecting drug users

Jacqueline Kaye Flynn, Rachel Sacks-Davis, Peter Gregory Higgs, Campbell Kynoch Aitken, Sarah Moneer, Vijayaprakash Suppiah, Samantha Lilly Tracy, Rosemary Ann Ffrench, Scott Bowden, Heidi Edelgard Drummer, Jacob George, Mandvi Bharadwaj, Margaret Elena Hellard

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Detectable HCV-specific cellular immune responses in HCV antibody and RNA negative people who inject drugs (PWID) raise the question of whether some are resistant to HCV infection. Immune responses from people who have been exposed to hepatitis C virus (HCV) and remain anti-HCV negative are of interest for HCV vaccine development; however, limited research addresses this area. Objectives: In a cohort of HCV antibody and RNA negative PWID, we assessed whether the presence of HCV-specific IFN-? responses or genetic associations provide any evidence of protection from HCV infection. Patients and Methods: One hundred and ninety-eight participants were examined longitudinally for clinical, behavioral, social, environmental and genetic characteristics (IFNL3 genotype [formally IL-28B] and HLA type). Sixty-one of the 198 participants were HCV antibody and RNA negative, with 53 able to be examined longitudinally for HCV-specific IFN-? ELISpot T cell responses. Results: Ten of the 53 HCV antibody and RNA negative participants had detectable HCV-specific IFN-? responses at baseline (18 ). The magnitude of IFN-? responses averaged 131 +/- 96 SFC/106 PBMC and the breadth was mean 1 +/- 1 pool positive. The specificity of responses were mainly directed to E2, NS4b and NS5b. Participants with (10) and without (43) HCV-specific IFN-? responses did not differ in behavioral, clinical or genetic characteristics (P > 0.05). There was a larger proportion sharing needles (with 70 , without 49 , P = 0.320) and a higher incidence of HCV (with 35.1 per 100 py, 95 CI 14.6, 84.4, without 16.0 per 100 py, 95 CI 7.2, 35.6, P = 0.212) in those with IFN-? responses, although not statistically significant. Half the participants with baseline IFN-? responses became HCV RNA positive (5/10), with one of these participants spontaneously clearing HCV. The spontaneous clearer had high magnitude and broad Th1 responses, favorable IFNL3 genotype and favorable HLA types. Conclusion
Original languageEnglish
Pages (from-to)1 - 14
Number of pages14
JournalHepatitis Monthly
Volume14
Issue number1 (Art. ID: e14678)
DOIs
Publication statusPublished - 2014

Cite this

@article{119b7ec068be41de9ea96f27d63ec480,
title = "Detection of HCV-specific IFN-gamma responses in HCV antibody and HCV RNA negative injecting drug users",
abstract = "Detectable HCV-specific cellular immune responses in HCV antibody and RNA negative people who inject drugs (PWID) raise the question of whether some are resistant to HCV infection. Immune responses from people who have been exposed to hepatitis C virus (HCV) and remain anti-HCV negative are of interest for HCV vaccine development; however, limited research addresses this area. Objectives: In a cohort of HCV antibody and RNA negative PWID, we assessed whether the presence of HCV-specific IFN-? responses or genetic associations provide any evidence of protection from HCV infection. Patients and Methods: One hundred and ninety-eight participants were examined longitudinally for clinical, behavioral, social, environmental and genetic characteristics (IFNL3 genotype [formally IL-28B] and HLA type). Sixty-one of the 198 participants were HCV antibody and RNA negative, with 53 able to be examined longitudinally for HCV-specific IFN-? ELISpot T cell responses. Results: Ten of the 53 HCV antibody and RNA negative participants had detectable HCV-specific IFN-? responses at baseline (18 ). The magnitude of IFN-? responses averaged 131 +/- 96 SFC/106 PBMC and the breadth was mean 1 +/- 1 pool positive. The specificity of responses were mainly directed to E2, NS4b and NS5b. Participants with (10) and without (43) HCV-specific IFN-? responses did not differ in behavioral, clinical or genetic characteristics (P > 0.05). There was a larger proportion sharing needles (with 70 , without 49 , P = 0.320) and a higher incidence of HCV (with 35.1 per 100 py, 95 CI 14.6, 84.4, without 16.0 per 100 py, 95 CI 7.2, 35.6, P = 0.212) in those with IFN-? responses, although not statistically significant. Half the participants with baseline IFN-? responses became HCV RNA positive (5/10), with one of these participants spontaneously clearing HCV. The spontaneous clearer had high magnitude and broad Th1 responses, favorable IFNL3 genotype and favorable HLA types. Conclusion",
author = "Flynn, {Jacqueline Kaye} and Rachel Sacks-Davis and Higgs, {Peter Gregory} and Aitken, {Campbell Kynoch} and Sarah Moneer and Vijayaprakash Suppiah and Tracy, {Samantha Lilly} and Ffrench, {Rosemary Ann} and Scott Bowden and Drummer, {Heidi Edelgard} and Jacob George and Mandvi Bharadwaj and Hellard, {Margaret Elena}",
year = "2014",
doi = "10.5812/hepatmon.14678",
language = "English",
volume = "14",
pages = "1 -- 14",
journal = "Hepatitis Monthly",
issn = "1735-143X",
number = "1 (Art. ID: e14678)",

}

Detection of HCV-specific IFN-gamma responses in HCV antibody and HCV RNA negative injecting drug users. / Flynn, Jacqueline Kaye; Sacks-Davis, Rachel; Higgs, Peter Gregory; Aitken, Campbell Kynoch; Moneer, Sarah; Suppiah, Vijayaprakash; Tracy, Samantha Lilly; Ffrench, Rosemary Ann; Bowden, Scott; Drummer, Heidi Edelgard; George, Jacob; Bharadwaj, Mandvi; Hellard, Margaret Elena.

In: Hepatitis Monthly, Vol. 14, No. 1 (Art. ID: e14678), 2014, p. 1 - 14.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Detection of HCV-specific IFN-gamma responses in HCV antibody and HCV RNA negative injecting drug users

AU - Flynn, Jacqueline Kaye

AU - Sacks-Davis, Rachel

AU - Higgs, Peter Gregory

AU - Aitken, Campbell Kynoch

AU - Moneer, Sarah

AU - Suppiah, Vijayaprakash

AU - Tracy, Samantha Lilly

AU - Ffrench, Rosemary Ann

AU - Bowden, Scott

AU - Drummer, Heidi Edelgard

AU - George, Jacob

AU - Bharadwaj, Mandvi

AU - Hellard, Margaret Elena

PY - 2014

Y1 - 2014

N2 - Detectable HCV-specific cellular immune responses in HCV antibody and RNA negative people who inject drugs (PWID) raise the question of whether some are resistant to HCV infection. Immune responses from people who have been exposed to hepatitis C virus (HCV) and remain anti-HCV negative are of interest for HCV vaccine development; however, limited research addresses this area. Objectives: In a cohort of HCV antibody and RNA negative PWID, we assessed whether the presence of HCV-specific IFN-? responses or genetic associations provide any evidence of protection from HCV infection. Patients and Methods: One hundred and ninety-eight participants were examined longitudinally for clinical, behavioral, social, environmental and genetic characteristics (IFNL3 genotype [formally IL-28B] and HLA type). Sixty-one of the 198 participants were HCV antibody and RNA negative, with 53 able to be examined longitudinally for HCV-specific IFN-? ELISpot T cell responses. Results: Ten of the 53 HCV antibody and RNA negative participants had detectable HCV-specific IFN-? responses at baseline (18 ). The magnitude of IFN-? responses averaged 131 +/- 96 SFC/106 PBMC and the breadth was mean 1 +/- 1 pool positive. The specificity of responses were mainly directed to E2, NS4b and NS5b. Participants with (10) and without (43) HCV-specific IFN-? responses did not differ in behavioral, clinical or genetic characteristics (P > 0.05). There was a larger proportion sharing needles (with 70 , without 49 , P = 0.320) and a higher incidence of HCV (with 35.1 per 100 py, 95 CI 14.6, 84.4, without 16.0 per 100 py, 95 CI 7.2, 35.6, P = 0.212) in those with IFN-? responses, although not statistically significant. Half the participants with baseline IFN-? responses became HCV RNA positive (5/10), with one of these participants spontaneously clearing HCV. The spontaneous clearer had high magnitude and broad Th1 responses, favorable IFNL3 genotype and favorable HLA types. Conclusion

AB - Detectable HCV-specific cellular immune responses in HCV antibody and RNA negative people who inject drugs (PWID) raise the question of whether some are resistant to HCV infection. Immune responses from people who have been exposed to hepatitis C virus (HCV) and remain anti-HCV negative are of interest for HCV vaccine development; however, limited research addresses this area. Objectives: In a cohort of HCV antibody and RNA negative PWID, we assessed whether the presence of HCV-specific IFN-? responses or genetic associations provide any evidence of protection from HCV infection. Patients and Methods: One hundred and ninety-eight participants were examined longitudinally for clinical, behavioral, social, environmental and genetic characteristics (IFNL3 genotype [formally IL-28B] and HLA type). Sixty-one of the 198 participants were HCV antibody and RNA negative, with 53 able to be examined longitudinally for HCV-specific IFN-? ELISpot T cell responses. Results: Ten of the 53 HCV antibody and RNA negative participants had detectable HCV-specific IFN-? responses at baseline (18 ). The magnitude of IFN-? responses averaged 131 +/- 96 SFC/106 PBMC and the breadth was mean 1 +/- 1 pool positive. The specificity of responses were mainly directed to E2, NS4b and NS5b. Participants with (10) and without (43) HCV-specific IFN-? responses did not differ in behavioral, clinical or genetic characteristics (P > 0.05). There was a larger proportion sharing needles (with 70 , without 49 , P = 0.320) and a higher incidence of HCV (with 35.1 per 100 py, 95 CI 14.6, 84.4, without 16.0 per 100 py, 95 CI 7.2, 35.6, P = 0.212) in those with IFN-? responses, although not statistically significant. Half the participants with baseline IFN-? responses became HCV RNA positive (5/10), with one of these participants spontaneously clearing HCV. The spontaneous clearer had high magnitude and broad Th1 responses, favorable IFNL3 genotype and favorable HLA types. Conclusion

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909641/pdf/hepatmon-14-01-14678.pdf

U2 - 10.5812/hepatmon.14678

DO - 10.5812/hepatmon.14678

M3 - Article

VL - 14

SP - 1

EP - 14

JO - Hepatitis Monthly

JF - Hepatitis Monthly

SN - 1735-143X

IS - 1 (Art. ID: e14678)

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