HUMORAL AND CELLULAR IMMUNE REACTIVITY TO RECOMBINANT MYCOBACTERIUM-LEPRAE ANTIGENS IN HLA-TYPED LEPROSY PATIENTS AND HEALTHY CONTROLS

In our search for Mycobacterium leprae antigens that might specificall y induce immunity or immunopathology, we have tested both humoral and cellular immune reactivity against purified recombinant M. leprae anti gens in 29 paucibacillary (PB), 26 multibacillary (MB) leprosy patient s, and 47 matched healthy contacts. The following M. leprae antigens w ere tested: 2L-1 (65L-1, GroE1-1), 2L-2 (65L-2, GroE1-2), 4L (SoDA), 4 3L, 10L (B) and 25L (Sra). The individuals were also typed for HLA-DRB 1 and DQB1 in order to see whether leprosy status and/or immune reacti vity to these antigens might be associated with certain HLA types. We also tested sera from another 48 patients before, during and after mul tidrug therapy (MDT) to study the relationship between antibody reacti vity to recombinant M. leprae antigens and MDT. Antibody titers to the four recombinant M. leprae antigens tested and to D-BSA were higher i n MB patients compared to PB patients and healthy controls, and declin ed with treatment. From a diagnostic or monitoring point of view none of the recombinant antigens seemed to be an improvement over D-BSA, ma inly due to the lower sensitivity. IgG subclasses were measured in pos itive sera of untreated patients. These were mainly of the IgG1 and Ig G3 subclasses, but subclass diversity was also observed and antigen de pendent: all four subclasses could be detected against 10L (B), only I gG1 and IgG3 against 43L and only IgG1 against 25L and 2L-1. Cellular immune reactivity against the purified recombinant M. leprae antigens was measured in a lymphocyte stimulation test (LST). As for M. leprae, there was an inverse correlation between antibody and T-cell reactivi ty. However, the number of LST responders to recombinant antigens was much lower than to M. leprae. The 43L antigen was recognized most ofte n (19%-24% of individuals tested) and more often than the 10L (B) anti gen (10%-12%). No clear correlation was observed with leprosy type or protection and, in general, M. leprae nonresponders were also negative with recombinant antigens. Finally, we confirmed that HLA-DRB102 is associated with leprosy in this population, and we observed an associa tion between DQB10601 and lepromatous leprosy. The number of positive individuals was too small to allow a meaningful analysis of the relat ionship between HLA type and immune reactivity. Although these data do not allow a conclusion as to one of these purified recombinant antige ns being either protection or disease related, the antigen-dependent I gG subclass diversity warrants further study on antigen-specific quali tative differences in immune reactivity that may be relevant for the o utcome of an infection with M. leprae.