Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil

Abstract

BackgroundEvidence suggests that human leukocyte antigen (HLA) alleles influence the host immune response against Mycobacterium leprae. However, the association between HLA alleles and borderline (B) leprosy has not been studied. The aim of this study was to determine whether HLA class I and II molecules are associated with susceptibility or resistance to B leprosy including borderline-tuberculoid (BT), borderline-borderline (BB), and borderline-lepromatous (BL).MethodsDNA was obtained by the salting-out technique from the blood samples of 202 patients with B leprosy and 478 control subjects. HLA class I (A*, B*, and C* loci) and class II (DRB1* and DQB1* loci) genotypes were determined by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers.ResultsThe case-controlled analysis results showed a significant association between B leprosy and HLA-C*05 (5.94% vs. 14.02%; p = 0.002, OR = 0.38, 95% CI = 0.20–0.73, pc = 0.032) and HLA-DRB1*07 (16.34% vs. 26.77%; p = 0.003, OR = 0.53, 95% CI = 0.3–0.8, pc = 0.039). A protective association was observed between BL leprosy and HLA-DQB1*02 (18.18% vs. 39.53%; p = 0.005, OR = 0.34, 95% CI = 0.15–0.75, pc = 0.025). In reactional patients, a significant association was observed between HLA-B*15 (28.72% vs. 12.76%; p = 0.011, OR = 2.75, 95% CI = 1.30–5.85, pc = 0.352) and predisposition to reversal reaction. Haplotype analysis showed that A*02-B*07-C*07-DRB1*15-DQB1*06 (2.97% vs. 1.04%; p = 0.015) and A*02-B*40-C*03-DRB1*13-DQB1*06 (1.73% vs. 0.10%; p = 0.0011) were associated with susceptibility to the B form. The presence of the HLA-DRB1*02 or HLA-DRB1*03/HLA-DQB1*01 haplotypes in B patients (22.05% vs. 33.0%; p = 0.005) suggested the involvement of these haplotypes in this clinical form of the disease.ConclusionsThe results indicate the involvement of HLA class I and class II molecules in B leprosy and reversal reactions; it also suggest a role for HLA in polarization of the disease in this group of patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0751-0) contains supplementary material, which is available to authorized users.

Advances in the Immunology and Genetics of Leprosy

“…The involvement of HLA complex in leprosy has been demonstrated immunologically and genetically, but genetic studies of HLA genes in borderline leprosy and leprosy reactions were rarely reported. de Souza-Santana et al (122) genotyped the HLA class I (A * , B * , and C * ) and class II (DRB1 * and DQB1 * ) loci in a cohort consisting of 202 borderline leprosy (BT, BB, BL) patients of which 94 had T1R and 478 healthy controls (122). Their results demonstrated that HLA-C * 05, HLA-DRB1 * 07, and HLA-DQB1 * 02 were genetically associated with borderline leprosy, while HLA-B * 15 showed a significantly high frequency in T1R (122).…”

“…de Souza-Santana et al (122) genotyped the HLA class I (A * , B * , and C * ) and class II (DRB1 * and DQB1 * ) loci in a cohort consisting of 202 borderline leprosy (BT, BB, BL) patients of which 94 had T1R and 478 healthy controls (122). Their results demonstrated that HLA-C * 05, HLA-DRB1 * 07, and HLA-DQB1 * 02 were genetically associated with borderline leprosy, while HLA-B * 15 showed a significantly high frequency in T1R (122). Since the association between HLA and T1R is rarely reported in the literature, these results need further confirmation in different populations.…”

“…Several members belonging to the classical class I and class II HLA genes have been shown to be associated with leprosy. Leprosyassociated class I HLA genes include HLA-A * 28 in Mestizo populations (121) and HLA-B * 15 and HLA-C * 05 in the Brazilian population (122). Leprosy-associated class II HLA genes include HLA-DQA1 in Brazilians (123), HLA-DQB1 * 06 and HLA-DQB1 * 07 in Mestizo populations (121), HLA-DRB1 * 11 in Brazilians (124), HLA-DRB1 * 1501 in Chinese and Indians (125,126), and HLA-DRB1 * 1501 in Indians (125,126).…”

Recombinant polypeptide of Mycobacterium leprae as a potential tool for serological detection of leprosy

“…The spectrum of outcomes following M. leprae infection is determined by host factors (van Hooij et al 2019) ranging from anti-inflammatory T helper-2 (Th2)-mediated immunity against high bacterial loads and antibodies against M. leprae antigens in MB leprosy to strong pro-inflammatory T helper-1 (Th1) and T helper-17 (Th17)-mediated immunity characteristic of PB leprosy (Saini et al 2013). The human leukocyte antigen (HLA) alleles are also hypothesized to influence host immune responses against M. leprae infection (de Souza-Santana et al 2015). Thus, a reliable diagnostic test for leprosy should be able to capture the different clinical outcomes of M. leprae infection, including both cellular and humoral markers (van Hooij et al 2019).…”

HLA Alleles are Genetic Markers for Susceptibility and Resistance towards Leprosy in a Mexican Mestizo Population

“…Functional assays have demonstrated that HLA‐DR, ‐DP, and ‐DQ are involved in the restricted recognition of M. leprae antigens by human TH1 and regulatory lymphocytes (Mutis et al., ). A large number of family‐ and population‐based association studies have shown an influence of HLA class I and II alleles towards susceptibility and protection to leprosy (Ottenhoff & de Vries, ; Geluk & Ottenhoff, ; Alcais et al., ; de Souza‐Santana et al., ). Although DR antigens seem to be important for the subtype of leprosy developed, their involvement in leprosy is still unclear.…”