World Journal of AIDS, 2011, 1, 136-138
doi:10.4236/wja.2011.14019 Published Online December 2011 (http://www.SciRP.org/journal/wja)
Copyright © 2011 SciRes. WJA
Role of HLA-A, HLA-B, HLA-DRB1 and
HLADQB1 Alleles in HIV-1 Patients with
Pulmonary Tuberculosis Co-Infection from
U. Shankarkumar*, A. Shankarkumar
National Institute of Immunohaematology, ICMR, KEM Hospital, Mumbai, India.
Received August 20th, 2011; revised September 27th, 2011; accepted October 14th, 2011.
We attempted to study the role of HLA HLA-A, B, DRB1 and DQB1 in HIV-1 patient’s co infected with pulmonary tu-
berculosis (PTB). A total of 102 HIV-1+ patients co-infected with pulmonary tuberculosis and 200 healthy controls
were included in HLA analysis. HLA-A*, HLA-B* HLA-DRB1* and DQB1* typing was done molecularly by PCR-
SSOP (Polymerase Chain reaction-Sequence Specific Oligonucleotide Probing ) method using kit (Dynal Kit-Invitrogen).
The frequencies of the HLA-A, B HLA-DRB, 1 and DQB1 alleles were determined using standard software. The HLA
alleles identified among HIV+ve/PTB+ve co-infected patien ts as compared with h ealth y con tro ls sho wed a significa ntly
increased frequency of HLA-B*08:01:01 in HIV+ve/PTB+ve co-infected patients when compared with healthy con trols
(p = 0.011, OR 3.335, 95% CI 1.35 - 8.18), Likewise HLA-DQB1*03:01:03 was significantly increased in HIV+
ve/PTB+ve co-infected patients as against healthy controls (p < 0.0001, OR 107.5, 95% CI 6.195 - 1865.3). Similarly
HLA-DQB*06:01:02 allele frequency was observed in HIV + ve/PTB + ve co-infected patients as against healthy con-
trols (p = 0.003, OR 4.808, 95% CI 1.72 - 13.39), HLA-DQB1*03:01:01 (p = 0.045, OR 0.219, 95% CI 0.051 - 0.940),
HLA-DQB1*06:01:01:01 (p = 0.012, OR 0.334, 95% CI 0.145 - 0.770), alleles in HIV+ve/PTB+ve co-infected patients
when compared with healthy controls. We can be concluded that different HLA alleles may render susceptibility or
protection to in different ethnic popu lation.
Keywords: HIV 1, PTB, Co-Infection, HLA, Western India
Acquired immunodeficiency syndrome (AIDS) caused
by HIV infection is endemic all over the globe and it is
on the rise especially in resource limited countries. Over
33 million people are living with HIV, 2.5 million are
newly infected and 2.1 million people have died of
AIDS . Individuals with impaired cell mediated im-
munity due to AIDS have a greatly increased risk of
co-infection with Mycobacterium tuberculosis [1-2]. The
co-infection of HIV-1 and Mycobacterium tuberculosis
causes two infectious diseases endangering human
healt h s ign ificantly. The pathogenesis of HIV-1 and PTB
co-infection is unavailable. The factors influencing the
greater inter individual variability to susceptibility to PTB
co-infection and progression of AIDS is yet to be identified.
This may be due to considerable varied immune re-
sponses of HIV-1 and MTB exposed individuals may
result from the different genetic background. MHC
class-I restricted CD8+ T cells are important for the gen-
eration of protective immune response in Mycobacterium
tuberculosis infection. CD8+ CTL (Cytotoxic T lym-
may be especially important
both for cells lacking MHC class-II molecules.
2. Materials and Methods
Both HLA Class I and class II genes have been shown to
be associated with susceptibility or resistance to HIV
infection . Among the HLA Class-II alleles, HLA-
DQB1 and HLA-DBP1 alleles have shown to be associ-
ated with HIV infection [4,5]. However, we have much
less information about the HLA linked genetic control of
susceptibility to HIV-1 and MTB co-infection. We have
Role of HLA-A, HLA-B, HLA-DRB1 and HLADQB1 Alleles in HIV-1 Patients with Pulmonary 137
Tuberculosis Co-Infection from Western India
attempted to study the role of HLA-A, B,DRB1 and
DQB1 in HIV-1 patients with pulmonary tuberculosis
(PTB). A total of 102 HIV-1+ patients co-infected with
pulmonary tuberculosis and 200 healthy controls were
included in HLA analysis. HLA typing was done mole-
cularly by PCR-SSOP (Polymerase Chain reaction-Se-
quence Specific Oligonucleotide Probing) method using
kit (Dynal Kit-Invitrogen). The frequencies of the HLA-
A, B, HLA-DRB1 and DQB1 alleles were determined by
using standard software.
The HLA class HLA and I class II alleles identified
among HIV+ve/PTB+ve co-infected patients as com-
pared with healthy controls are given in Table 1. Sig-
nificantly increased frequency of HLA-B*08:01:01 was
observed in HIV+ve/PTB+ve co-infected patients when
compared with healthy controls (p = 0.011, OR 3.335,
95% CI 1.35 - 8.18) Likewise HLA-DQB1* 03:01:03
was significantly increased in HIV+ve/PTB+ve co-in-
fected patients as against healthy controls (p < 0.0001,
OR 107.5, 95% CI 6.195 - 1865.3). Similarly HLA-
DQB*06:01:02 allele frequency was observed in HIV+
ve/PTB+ve co-infected patients as against healthy con-
trols (p = 0.003, OR 4.808, 95 % CI 1.72 - 13.39) , A sig-
nificantly increased frequency of HLA-A*02:11 (p =
0.015, OR 1.762, 95% CI 1.13 - 2.73), HLA-B*
57:01:01(p = 0.017, OR 1.973, 95% CI 1.15 - 3.37),
HLA-B*56:01:01 (p = 0.029, OR 2.606, 95% CI 1.16 -
5.85), HLA-DRB1*040301 (p = 0.006, OR 7.727, 95%
CI 1.79 - 33.3), HLA-DRB1*09:01:02 (p = 0.012, OR
9.143, 95% CI 1.63 - 51.174), HLA-DRB1*14:01:03 (p
= 0.024, OR 13.526, 95% CI 1.381 - 132.49), HLA-
DQB1*05:02:01 (p < 0.0001, OR 28.556, 95% CI 8.36 -
242.16), and a significantly decreased frequency was
observed in HLA-B*51:01:01 (p = 0.009, OR 0.434, 95%
CI 0.236 - 0.799), HLA-DQB1*03 :01:01 (p = 0.045, OR
0.219, 95% CI 0.051 - 0.940), HLA-DQB1*06:01:01:01
(p = 0.012, OR 0.334, 95% CI 0.145 - 0.770), alleles in
HIV+ve/PTB+ve co-infected patients when compared
with healthy controls.
We have studied, HLA-A, B, DRB and DQB loci to find
out the role of these HLA alleles in HIV+ve/PTB+ve
co-infection. Significantly increased frequency of HLA-
B*08:01:01 and HLA-DQB*03:01:03 in HIV+ve/PTB+
ve co-infected patients against controls may suggest that,
these alleles play an associative role in HIV infection
and PTB development. Our study reveals that,
HLA-B*08:01:01and HLA-DQB*03:01:03 are associa-
tive to enhance HIV infection. The decreased frequency
of HLA-DQB1*03:01:01 has been reported in PTB pa-
tients from China . In our study, HLA-DQB1*
03:01:01 is decreased in HIV+ve/PTB+ve co-infected
patients compared to controls sugg esting that it may play
a protective role in HIV+ve/PTB+ve co-infection.
Whereas HLA-DQB*03:01:03 is associative in HIV.
Among South Indians an increased frequency of HLA-
DQB1*06:01:01:01 has been reported in HIV-ve
PTB+ve and HIV+ve PTB+ve patients, suggesting that
HLA-DQB1**06:01:01:01 is associated with susceptibil-
ity to PTB as well as development of PTB in HIV pa-
tients . Further earlier association of HLA-DQB1*
06:01:01:01 with susceptibility to PTB has also been
reported in south India . In contrast to the above two
Table 1. Significant HLA alleles identified among the TB co-infected HIV patients from Western India.
HIV + PTB + (n = 102) vs controls (n = 200) HIV + PTB + (n = 102) vs controls (n = 200)
Increased frequency Decreased frequency
Copyright © 2011 SciRes. WJA
Role of HLA-A, HLA-B, HLA-DRB1 and HLADQB1 Alleles in HIV-1 Patients with Pulmonary
138 Tuberculosis Co-Infection from Western India
studies on South Indian population, it is reported that
HLA-DQB1*06:01:01:01 plays a protective role against
HIV disease progression in Europeans . In our study a
significantly increased frequency of HLA-DQB*06:01:
02 in HIV+ve/PTB+ve co-infected patients when com-
pared to controls and HIV+ve PTB-ve patients may suggest
its strong association with both HIV infection and PTB
co-infection. On the contrary HLA-DRB1* 06:01:01:01
frequency was significantly decreased in HIV+ve/PTB+
ve co-infected patients compared to controls, thereby
may protect from HIV infection and PTB development.
HLA-DQB1*05:02:01 allele is reportedly related to high
risk of developing TB in population from Asia and Latin
America . In the present study, frequency of HLA-
DQB1*05:02:01 is increased in HIV+ve/PTB+ve co-
infected patients compared to healthy subjects to show
that HLA-DQB1* 05:02:01 may be associated with
HIV+ve/PTB+ve co-infection. There was no consider-
able change in frequency of HLA-A*26:01:01 in HIV+
ve/PTB+ve co-infected patients when compared with
controls and decreased frequency was observed when
compared with HIV+ve PTB-ve patients. This suggests
that, HLA-A*26:01:01 may not be associated with HIV
infection and may play a protective role in PTB devel-
opment. HLA-A*31 and HLA-B*41 antigens and the
HLA-DRB1*10 and HLA-DQB1*05 were over repre-
sented in Brazilian patients with AIDS and tuberculosis,
suggesting association to tuberculosis with AIDS .
As reported earlier HLA-DRB1*13 is associated with sus-
ceptibility to HIV-1 infection whereas HLA- DQB1*02: 03
and DRB1*01 are resistant to HIV-1 infection which
may vary in differen t ethnic group s . HLA-DRB1* 15
is susceptible in PTB development and DRB1*11 may be
protective allele in Chinese population . In the present
study, HLA-DRB alleles HLA-DRB1*04:03:01, DRB1*
09:01:02, DRB1*14:01:03 and HLA-DQB1*05:02:01
allele are significantly increased in HIV+ve/PTB+ve
co-infected patients compared to healthy controls. Thus,
these alleles may be associated to susceptibility of HIV+
ve/PTB+ve co-infection among Indians.
It can be concluded that different HLA alleles may ren-
der susceptibility or pro tection to an infection in differen t
ethnic population. HLA alleles may influence immu-
nopathogenesis from either HIV and/or PTB infection.
Further study on the HIV progression and resistant TB
would enlighten the mechanism of action of the HLA in
HIV and PTB infection.
 Ministry of Health and Family Welfare, “National AIDS
Control Organization (NACO) Report 2008,” Govern-
ment of India News Letter, 2008.
 V. Vijayalakshmi, S. R. Shilpa, B. Anuradha, et al., “Role
of HLA-B51 and HLA-B52 in Susceptibility to Pulmo-
nary Tuberculosis,” Infection, Genetics and Evolution,
Vol. 6, No. 6, 2006, pp. 436-439.
 M. Carrington and S. J. O’Brien, “The Influence of HLA
Genotype on AIDS,” Annual Review of Medicine, Vol. 54,
2003, pp. 535-551.
 A. P. Achord, R. E. Lewis, M. N. Brackin, et al., “HIV-1
Disease Association with HLA-DQ Antigen in Africans
Americans and Caucasians,” Pathobiology, Vol. 64, No.
4, 1996, pp. 204-208. doi:10.1159/000164049
 N. Odum, J. Georgsen, L. Fugger, et al., “HLA-DP Anti-
gens in HIV Infected Individuals,” Disease Markers, Vol.
8, No. 3, 1990, pp. 113-116.
 J. Wang, C. Song and S. Wang, “Association of HLA-
DRB1 Genes with Pulmonary Tuberculosis,” Chinese Jour-
nal of Tuberculosis and Respiratory Disease, Vol. 24, No.
5, 2001, pp. 302-305.
 P. Selvaraj, S. Ragavan, S. Swaminathan, et al., “HLA-
DQB-1 and HLA-DPB-1 Allele Profile in HIV Patients
Infected with or without Pulmonary Tuberculosis of
South India,” Infection, Genetics and Evolution, Vol. 8,
No. 5, 2008, pp. 664-671.
 M. Ravikumar, V. Dheenadhayalan, K. Rajaram, et al.,
“Associations of HLA-DRB1, DQB1 and DPB1 Alleles
with Pulmonary Tuberculosis in South India,” Tubercle
and Lung Disease, Vol. 79, No. 5, 1999, pp. 309-317.
 A. Vyakarnam, D. Sidebottom, S. Murud, et al., “Posses-
sion of Human Leucocytes Antigen DQ6 Alleles and the
Rate of CD4 T-Cell Decline in Human Immunodeficiency
Virus-1 Infection,” Immunology, Vol. 112, No. 1, 2004,
pp. 136-142. doi:10.1111/j.1365-2567.2004.01848.x
 A. Dubaniewicz, G. Moszhowska and Z. Szczerkowska,
“Frequency of DRB1-DQB1 Two Locus Haplotypes in
Tuberculosis: Preliminary Report,” Tuberculosis, Vol. 85,
No. 4, 2005, pp. 259-267.
 J. F. Fernando de castro, V. R. Maria de Lourdes, S. D.
Neifi Hassam, et al., “HLA Profile in Pati ents with AIDS
and Tuberculosis,” The Brazilian Journal of Infectious
Diseases, Vol. 12, No. 4, 2008, pp. 278-280.
 M. Patricia, M. Karina, S. Adrian, et al., “Association of
HLA-DQ and HLA-DR Alleles with Susceptibility or
Resistance to HIV-1 Infection among Population of
Chaco Province, Argentina,” Medicina, Vol. 62, No. 3,
2002, pp. 245-248.
Copyright © 2011 SciRes. WJA