Humoral and cellular immune reactivity to recombinant M. leprae antigens in HLA-typed leprosy patients and healthy controls.

In our search for Mycobacterium leprae antigens that might specifically induce immunity or immunopathology, we have tested both humoral and cellular immune reactivity against purified recombinant M. leprae antigens in 29 paucibacillary (PB), 26 multibacillary (MB) leprosy patients, and 47 matched healthy contacts. The following M. leprae antigens were tested: 2L-1 (65L-1, GroEl-1), 2L-2 (65L-2, GroEl-2), 4L (SoDA), 43L, 10L (B) and 25L (Sra). The individuals were also typed for HLAD-RB1 and DQB1 in order to see whether leprosy status and/or immune reactivity to these antigens might be associated with certain HLA types. We also tested sera from another 48 patients before, during and after multidrug therapy (MDT) to study the relationship between antibody reactivity to recombinant M. leprae antigens and MDT. Antibody titers to the four recombinant M. leprae antigens tested and to D-BSA were higher in MB patients compared to PB patients and healthy controls, and declined with treatment. From a diagnostic or monitoring point of view none of the recombinant antigens seemed to be an improvement over D-BSA, mainly due to the lower sensitivity. IgG subclasses were measured in positive sera of untreated patients. These were mainly of the IgG1 and IgG3 subclasses, but subclass diversity was also observed and antigen dependent: all four subclasses could be detected against 10L (B), only IgG1 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 reactivity. However, the number of LST responders to recombinant antigens was much lower than to M. leprae. The 43L antigen was recognized most often (19%-24% of individuals tested) and more often than the 10L (B) antigen (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-DRB1*02 is associated with leprosy in this population, and we observed an association between DQB1*0601 and lepromatous leprosy. The number of positive individuals was too small to allow a meaningful analysis of the relationship between HLA type and immune reactivity. Although these data do not allow a conclusion as to one of these purified recombinant antigens being either protection or disease related, the antigen-dependent IgG subclass diversity warrants further study on antigen-specific qualitative differences in immune reactivity that may be relevant for the outcome of an infection with M. leprae.