Tuberculoid leprosy in Mexicans is associated with HLA-DR3

Abstract

S ummary HLA-A, B, C, and DR antigens were investigated in a total group of 76 leprosy patients, classified according to the system of Ridley and Jopling in 30 IT and 46 LL individuals. A group of 100 healthy subjects were included for comparison. Patients and controls were all Mexican Mestizos born and inhabitants of Mexico. Typing of blood group systems was also performed. All IT patients showed a positive lepromin skin test, while all LL patients were negative to the specific antigen. The distribution of red-ceIl antigens was similar in both groups. The results of HLA typing demonstrated a significant association of DR3 with the tuberculoid type (X2 = 11•85; p=0'0007; pc = 0•04). The RR value for DR3 carriers was 4•93 and the EF was 0•24. It is concluded that a Class 11linked susceptibility gene plays an important role in the expression of tuberculoid leprosy. This gene is closely linked to DR3 in the Mexican population. A considerable number of studies have been reported looking for an association between leprosy and gene products of the major histocompatibility complex (MHC) in humans. Firstly, concerning the HLA class I antigens, 1-1 0 and later to the molecules belonging to the 0 region.I J-1 6 An analysis of the published results up to 1983 has been reviewed by Serjeantson et al. J7 Even though technical problems in HLA typing were sometimes evident, and the control group matching or the disease classification were not strictly considered, and a consistent association between A or B antigens could not be established from population studies, inheritance of HLA haplotypes in fa milies provided evidence of the participation of HLA genes in the sus c eptibility to leprosy. 1 7-2 1 Typing of class II products, which include HLA DR, DQ and DP antigens, clearly showed the relationship between DR antigens and tuberculoid leprosyll-1 6 in random population as well as in fa milies. Leprosy in Mexico is an endemic disease with an incidence of 21/100,000 inhabitants and the patients are mainly located in the central plateau and the west area of the country .22 The most common type of leprosy according to the classification of Ridley and Jopling23 is the lepromatous fo rm; 62% of the cases are LL and BL, 23% are BB and only 15% are IT and BT.2 4 For this reason, the first group we studied in 19732 looking for genetic factors was of LL patients. At that time, we fo und a decrease of A2 and A3, but only 8 antigens were explored. In a fu rther work done by us in

Association of genetic polymorphism of HLA-DRB1 antigens with the susceptibility to lepromatous leprosy

“…It was previously demonstrated that, in Mexicans, the HLA-DRB1*03 allele is associated with the TT clinical subgroup (20) and a previous family study demonstrated an association of the HLA-DRB1*1501 allele with LL leprosy (21). In this study, we reported the association of the HLA-DRB1*01 allele with susceptibility to LL and D leprosy and we observed that the HLA-DRB1*08 allele was associated with protection against leprosy.…”

Genetics of susceptibility to leprosy

“…HLA-DR3 was associated with tuberculoid leprosy in Mexico 34 and in the South American populations of Surinam 35 and Venezuela, 10 whereas it was found at lower frequencies in lepromatous patients. 35,36 T-cell proliferation responses to certain epitopes of the mycobacterial hsp65 (p3-13) are DR3 restricted 37 and DR3 was associated with low T-cell responses to M. leprae in tuberculoid patients.…”

Study of HLA class II alleles by PCR oligotyping in leprosy patients from North India

“…Earlier studies have reported increased frequencies of HLA-DR2 and DQI in LL patients (2) and of HLA-DR3 in TT (3,4) patients. At the present time the serologically-Characterized HLA antigens can be further subdivided into variants defined by their sequence.…”