HLA-DR and HLA-DQ alleles in patients from the south of Brazil: markers for leprosy susceptibility and resistance.
BACKGROUND
Many epidemiological studies have shown that the genetic factors of the host play a role in the variability of clinical response to infection caused by M. leprae. With the purpose of identifying genes of susceptibility, the present study investigated the possible role of HLA-DRB1 and DQA1/DQB1 alleles in susceptibility to leprosy, and whether they account for the heterogeneity in immune responses observed following infection in a Southern Brazilian population.


METHODS
One hundred and sixty-nine leprosy patients and 217 healthy controls were analyzed by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers (One Lambda, CA, USA).


RESULTS
There was a positive association of HLA-DRB1*16 (*1601 and *1602) with leprosy per se (7.3% vs. 3.2%, P = 0.01, OR = 2.52, CI = 1.26-5.01), in accord with previous serological studies, which showed DR2 as a marker of leprosy. Although, HLA-DQA1*05 frequency (29.8% vs. 20.9%, P = 0.0424, OR = 1.61, CI = 1.09-2.39) was higher in patients, and HLA-DQA1*02 (3.0% vs. 7.5%, P = 0.0392, OR = 0.39, CI = 0.16 - 0.95) and HLA-DQA1*04 (4.0% vs. 9.1%, P = 0.0314, OR = 0.42, CI = 0.19 - 0.93) frequencies lower, P-values were not significant after the Bonferroni's correction. Furthermore, HLA-DRB1*1601 (9.0% vs. 1.8%; P = 0.0016; OR = 5.81; CI = 2.05-16.46) was associated with susceptibility to borderline leprosy compared to control group, and while HLA-DRB1*08 (11.2% vs. 1.2%; P = 0.0037; OR = 12.00; CI = 1.51 - 95.12) was associated with susceptibility to lepromatous leprosy, when compared to tuberculoid leprosy, DRB1*04 was associated to protection.


CONCLUSIONS
These data confirm the positive association of HLA-DR2 (DRB1*16) with leprosy per se, and the protector effect of DRB1*04 against lepromatous leprosy in Brazilian patients.
da Silva
Samira A
SA
Departamento de Análises Clínicas, Universidade Estadual de Maringá, Paraná, Brazil. samira_paes@hotmail.com
Mazini
Priscila S
PS
Reis
Pâmela G
PG
Sell
Ana M
AM
Tsuneto
Luiza T
LT
Peixoto
Paulo R
PR
Visentainer
Jeane E L
JE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001938:Brazil; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D015440:Leprosy, Lepromatous / Q000235:genetics* / Q000276:immunology; D015441:Leprosy, Tuberculoid / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055815:Young Adult
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains
Bull World Health Organ. 1966;34(6):827-57
5330347
Trends Microbiol. 1998 Apr;6(4):148-54
9587192
Tissue Antigens. 1987 Mar;29(3):146-53
3603547
Annu Rev Immunol. 1993;11:403-50
8476568
Int J Lepr Other Mycobact Dis. 2000 Mar;68(1):49-56
10834069
N Engl J Med. 2000 Sep 14;343(11):782-6
10984567
Tissue Antigens. 2005 May;65(5):437-47
15853898
Braz J Med Biol Res. 1997 Jan;30(1):51-9
9222403
Tuberculosis (Edinb). 2004;84(1-2):82-92
14670349
Enferm Infecc Microbiol Clin. 2007 Dec;25(10):627-31
18053473
Clin Dermatol. 2007 Mar-Apr;25(2):165-72
17350495
Tissue Antigens. 2007 Dec;70(6):455-63
17900288
J Biomed Biotechnol. 2003;2003(3):208-211
12975536
Curr Opin Immunol. 2005 Feb;17(1):44-8
15653309
Tissue Antigens. 1993 Sep;42(3):133-7
8284786
Tissue Antigens. 1992 May;39(5):225-35
1357775
Genes Immun. 2007 Jun;8(4):320-4
17396103
Evol Bioinform Online. 2007 Feb 23;1:47-50
19325852
Vox Sang. 1982;42(5):243-7
6954762
Int J Parasitol. 1999 Sep;29(9):1351-8
10579423
Genes Immun. 2001 Jun;2(4):196-204
11477474
Tissue Antigens. 1985 Oct;26(4):243-7
3878012
Genes Immun. 2004 Jan;5(1):63-7
14735151
Int J Dermatol. 2002 Oct;41(10):681-6
12390192
Clin Exp Dermatol. 2002 May;27(3):235-9
12072016
Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):177-82
12509516
Drug Metab Dispos. 2001 Apr;29(4 Pt 2):479-83
11259336
Microbes Infect. 2006 Apr;8(4):1124-31
16513393
Tissue Antigens. 1992 Sep;40(3):124-7
1440566
Hum Biol. 2000 Aug;72(4):597-617
11048789