Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 18, 2016; 8(29): 1212-1221
Published online Oct 18, 2016. doi: 10.4254/wjh.v8.i29.1212
Potential role of killer immunoglobulin receptor genes among individuals vaccinated against hepatitis B virus in Lebanon
Nada M Melhem, Rami A Mahfouz, Khalil Kreidieh, Rabab Abdul-Khalik, Rolla El-Khatib, Reem Talhouk, Umayya Musharrafieh, Ghassan Hamadeh
Nada M Melhem, Khalil Kreidieh, Rolla El-Khatib, Medical Laboratory Sciences Program, Faculty of Health Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
Rami A Mahfouz, Rabab Abdul-Khalik, Department of Pathology and Laboratory Medicine, Faculty of Medicine, American University of Beirut, Beirut 1107-2020, Lebanon
Reem Talhouk, Department of Health Management and Policy, Faculty of Health Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
Umayya Musharrafieh, Ghassan Hamadeh, Department of Family Medicine, Faculty of Medicine, American University of Beirut, Beirut 1107-2020, Lebanon
Author contributions: Melhem NM designed the study, performed the analysis and wrote the paper; Mahfouz RA contributed to the analysis; Kreidieh K and Abdul-Khalik R performed the experiments; El-Khatib R, Talhouk R, Musharrafieh U and Hamadeh G helped in the recruitment of participants.
Supported by The University Review Board at the American University of Beirut, No. A88507; and the Lebanese National Council for Scientific Research, No. A522185.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board (IRB) of the American University of Beirut.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: Not applicable.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Nada M Melhem, PhD, Associate Professor of Infectious Diseases and Microbiology, Medical Laboratory Sciences Program, Faculty of Health Sciences, American University of Beirut, 11-0236 Riad El Solh, Beirut 1107-2020, Lebanon. melhemn@aub.edu.lb
Telephone: +961-1-350000-4699 Fax: +961-1-744470
Received: February 16, 2016
Peer-review started: February 18, 2016
First decision: March 30, 2016
Revised: April 13, 2016
Accepted: July 11, 2016
Article in press: July 13, 2016
Published online: October 18, 2016
Processing time: 240 Days and 13.8 Hours
Abstract
AIM

To explore the role of killer immunoglobulin receptor (KIR) genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus.

METHODS

We recruited 101 voluntary participants between March 2010 and December 2011. Sera samples from vaccinated and non-vaccinated participants were tested for the presence of anti-HBs antibodies as a measure of protection against hepatitis B, hepatitis B surface antigen and hepatitis B core antibody as indicators of infection by enzyme-linked immunosorbent assay. KIR gene frequencies were determined by polymerase chain reaction.

RESULTS

Sera samples from 99 participants were tested for the levels of anti-HBs as an indicator of protection (≥ 10 mIU/mL) following vaccination as defined by the World Health Organization international reference standard. Among the vaccinated participants, 47% (35/74) had anti-HBs titers above 100 mIU/mL, 22% (16/74) had anti-HBs ranging between 10-100 mIU/mL, and 20% (15/74) had values of less than 10 mIU/mL. We report the lack of significant association between the number of vaccine dosages and the titer of antibodies among our vaccinated participants. The inhibitory KIR2DL1, KIR2DL4, KIR3DL1, KIR3DL2, and KIR3DL were detected in more than 95%, whereas KIR2DL2, KIR2DL3, KIR2DL5 (KR2DL5A and KIR2DL5B) were expressed in 56%, 84% and 42% (25% and 29%) of participants, respectively. The observed frequency of the activating KIR genes ranged between 35% and 55% except for KIR2DS4, detected in 95% of the study participants (40.6% 2DS4*001/002; 82.2% 2DS4*003/007). KIR2DP1 pseudogene was detected in 99% of our participants, whereas KIR3DP*001/02/04 and KIR3DP1*003 had frequencies of 17% and 100%, respectively. No association between the frequency of KIR genes and anti-HBs antibodies was detected. When we compared the frequency of KIR genes between vaccinated individuals with protective antibodies titers and those who lost their protective antibody levels, we did not detect a significant difference. KIR2DL5B was significantly different among different groups of vaccinated participants (group I > 100 mIU/mL, group II 10-100 mIU/mL, group III < 10 mIU/mL and group IV with undetectable levels of protective antibodies).

CONCLUSION

To our knowledge, this is the first study screening for the possible role of KIR genes among individuals vaccinated against hepatitis B virus (HBV). Our results can be used to design larger studies to better understand the role of KIR genes in protection against or susceptibility to HBV post vaccination.

Keywords: Hepatitis B virus; Killer immunoglobulin receptors; Hepatitis B vaccine; Lebanon; Natural killer cells

Core tip: Currently, there are no data supporting the use of booster doses of hepatitis B vaccine among immuno-competent individuals responding to a complete primary vaccination regimen. Importantly, 5%-10% of healthy adults do not generate protective levels of antibodies and are hence considered non-responders. This study aims to explore the role of killer immunoglobulin receptor genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus.