Role of HLA-A, HLA- B, HLA-DRB1 and HLADQB1 Alleles in HIV-1 Patients with Pulmonary Tuberculosis Co-Infection from Western India

doi:10.4236/wja.2011.14019

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World Journal of AIDS, 2011, 1, 136-138

doi:10.4236/wja.2011.14019 Published Online December 2011 (http://www.SciRP.org/journal/wja)

Role of HLA-A, HLA-B, HLA-DRB1 and

HLADQB1 Alleles in HIV-1 Patients with

Pulmonary Tuberculosis Co-Infection from

Western India

U. Shankarkumar*, A. Shankarkumar

National Institute of Immunohaematology, ICMR, KEM Hospital, Mumbai, India.

E-mail: *[email protected]

Received August 20th, 2011; revised September 27th, 2011; accepted October 14th, 2011.

ABSTRACT

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

1. Introduction

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 [1]. 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-

phocytes)—derived IFN-



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 [3]. 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.

3. Results

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.

4. Discussion

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 [6]. 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 [7]. Further earlier association of HLA-DQB1*

06:01:01:01 with susceptibility to PTB has also been

reported in south India [8]. 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

HLA-B*08:01:01 HLA-B*51:01:01

HLA-B*55:01:01 HLA-DQB1*03:01:01

HLA-B*57:01:01 HLA-DQB1*06:01:01

HLA-A*02:11

HLA-DRB1*04:03:01

HLA-DRB1*09:01:02

HLA-DRB1*14:01:03

HLA-DQB1*03:01:03

HLA-DQB1*06:01:02

HLA-DQB1*05:02:01

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 [9]. 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 [10]. 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 [11].

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 [12]. HLA-DRB1* 15

is susceptible in PTB development and DRB1*11 may be

protective allele in Chinese population [6]. 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.

5. Conclusions

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.

REFERENCES

[1] Ministry of Health and Family Welfare, “National AIDS

Control Organization (NACO) Report 2008,” Govern-

ment of India News Letter, 2008.

[2] 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.

doi:10.1016/j.meegid.2006.02.002

[3] M. Carrington and S. J. O’Brien, “The Influence of HLA

Genotype on AIDS,” Annual Review of Medicine, Vol. 54,

2003, pp. 535-551.

doi:10.1146/annurev.med.54.101601.152346

[4] 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

[5] 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.

[6] 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.

[7] 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.

doi:10.1016/j.meegid.2008.06.005

[8] 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.

doi:10.1054/tuld.1999.0213

[9] 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

[10] 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.

doi:10.1016/j.tube.2004.12.003

[11] 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.

[12] 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.