Potential role of killer immunoglobulin receptor genes among individuals vaccinated against hepatitis B virus in Lebanon.
OBJECTIVE
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.KIRgene 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 activatingKIRgenes 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 ofKIRgenes and anti-HBs antibodies was detected. When we compared the frequency ofKIRgenes 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).


CONCLUSIONS
To our knowledge, this is the first study screening for the possible role ofKIRgenes among individuals vaccinated against hepatitis B virus (HBV). Our results can be used to design larger studies to better understand the role ofKIRgenes in protection against or susceptibility to HBV post vaccination.
Nada M Melhem, Khalil Kreidieh, Rolla El-Khatib, Medical Laboratory Sciences Program, Faculty of Health Sciences, American University of Beirut, Beirut 1107-2020, Lebanon.
Nada M
NM
Melhem
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
RA
Mahfouz
Nada M Melhem, Khalil Kreidieh, Rolla El-Khatib, Medical Laboratory Sciences Program, Faculty of Health Sciences, American University of Beirut, Beirut 1107-2020, Lebanon.
Khalil
K
Kreidieh
Nada M Melhem, Khalil Kreidieh, Rolla El-Khatib, Medical Laboratory Sciences Program, Faculty of Health Sciences, American University of Beirut, Beirut 1107-2020, Lebanon.
Rabab
R
Abdul-Khalik
Nada M Melhem, Khalil Kreidieh, Rolla El-Khatib, Medical Laboratory Sciences Program, Faculty of Health Sciences, American University of Beirut, Beirut 1107-2020, Lebanon.
Rolla
R
El-Khatib
Nada M Melhem, Khalil Kreidieh, Rolla El-Khatib, Medical Laboratory Sciences Program, Faculty of Health Sciences, American University of Beirut, Beirut 1107-2020, Lebanon.
Reem
R
Talhouk
Nada M Melhem, Khalil Kreidieh, Rolla El-Khatib, Medical Laboratory Sciences Program, Faculty of Health Sciences, American University of Beirut, Beirut 1107-2020, Lebanon.
Umayya
U
Musharrafieh
Nada M Melhem, Khalil Kreidieh, Rolla El-Khatib, Medical Laboratory Sciences Program, Faculty of Health Sciences, American University of Beirut, Beirut 1107-2020, Lebanon.
Ghassan
G
Hamadeh
Hepatitis B vaccine; Hepatitis B virus; Killer immunoglobulin receptors; Lebanon; Natural killer cells