GENETIC PATTERN OF MHC CLASS II ALLELES IN MEXICAN PATIENTS WITH LEPROSY

5.3
TITLE: GENETIC PATTERN OF MHC CLASS II ALLELES IN MEXICAN PATIENTS WITH LEPROSY

A. Munguia,¹ C. Alaez,¹ A. Camacho,¹ O. Flores,² M. Rodriguez,² O. Rodriguez,² C. Gorodezky.¹

¹Dept. of Immunogenetics, InDRE SSA; ²Centro Dermatol. Pascua, Mexico City, Mexico

The clinical spectrum of leprosy, spans tuberculoid leprosy (TT) and lepromatous leprosy (LL) forms, depending on the host specific cellular immune response (CIR) against M. Ieprae. TT is characterized by localized anesthetic skin lesions and low bacillary load. LL is a systemic progressive disease where specific cellular immunosuppression is evident and bacilli are abundant. In Surinam, Venezuela and Mexico, we and others reported DR3 associated with susceptibility in TT. We also showed that DQ1 segregated in siblings affected with LL, and in their lepromin non responding siblings. DQ1 suppression was also shown by us “in vitro”. The aim of this study was to investigate the distribution of DRB1, DQA1, DQB1 alleles and the polymorphism of the DQ regulatory loci (QAP/QBP) in LL Mexican patients. Diagnosis of LL was confirmed in biopsy specimens. All patients were anergic to lepromin using the Mitsuda skin test. DNA was extracted from peripheral blood samples. Typing was done using PCR–SSOP protocols of the 11th and 12th IHW. QAP/QBP promoter alleles were typed in 105 controls and 36 patients. One hundred and fourteen LL patients and 204 controls were typed for class II loci, aII of them Mexican Mestizos. DRB1*1501 (p = 0.005; OR = 2.9; EF = 0.15); DQA1*0102 (p = 0.007; OR = 2.2; EF = 0.16) and DQB1*0602 (p = 0.01; OR = 2.3; EF 0.12) were increased in patients. QAP–1.4 (p = 0.0009, OR = 10.5, EF = 0.18) and QBP–5.11/5.12 (p = 0.007, OR = 4.5, EF = 0.19) were also found increased in LL. These data show that the susceptibility to LL in Mexicans is partly due to the DRB1*1501–DQA1*0102–DQB1*0602 haplotype. DQB1*0602 is a subtype of DQ1. This antigen was previously found asssociated by some of us with CIR suppression. The association with the QBP alleles is consistent with the DRB1*1501 associated haplotype. QAP 1.4, a high risk allele which had a high OR, is present in DRB1*1301/*1302 haplotypes. These promoter polymorphisms may influence DQ expression, and therefore the amount of peptides presented to the T–cell receptor. This process may impact the induction of the Th1 or Th2 response that finally defines the leprosy spectrum.