ASSOCIATION OF C4B DEFICIENCY (C4B-ASTERISK-Q0) WITH ERYTHEMA-NODOSUMIN LEPROSY

A considerable number of studies have postulated significant associati ons between susceptibility to the different clinical manifestations of leprosy and the MHC. In this investigation, the association between t he MHC class III complement proteins C2, BF, C4A and C4B and leprosy i n a patient population of Southern Brazil was studied. A total of 109 non-related leprosy patients was investigated; 73 presented with lepro matous leprosy (LL), 46 of them had the immunopathological reaction of erythema nodosum (ENL), the remaining 36 were tuberculoid, borderline and indeterminate leprosy (TIBL) patients. The control group included 172 healthy individuals matched with the patients according to their ethnic and geographical origin. C2, BF, C4A and C4B allotypes were det ermined by standard technologies including Western blots for C2 and C4 variant alleles with monoclonal and polyclonal antibodies. Non-expres sed ('silent') C4 alleles in hemizygously deficient individuals were e stimated semiquantitatively on the basis of the C4A and C4B isotype ra tio and by the MASC ('minimal chi-square') method. The results showed a significantly elevated presence of the non-expressed C4B allele (C4B Q0) in the LL and ENL patient groups in comparison with the controls. The most significant difference was observed in the ENL group when co mpared with the controls. In addition, all patients who were homozygou sly C4B-deficient had ENL, and most of them had the BFF1 allele. The comparison between LL patients with and without ENL also showed a stat istically significant difference in the presence of C4BQO, indicating that C4B deficiency itself is associated with ENL. The relative risk of LL patients with the C4BQO allele suffering from ENL was 5.3 compa red with LL patients without C4BQO. Since immune complexes (IC) are c onsidered to be the pathogenic cause of ENL, our findings indicate tha t C4B deficiency may play an important role in the abnormal immune res ponse against Mycobacterium leprae and in the lack of IC clearance, le ading to ENL reactions. Individuals with this allele seem to be at a h igher risk of developing pathological immune reactivity in lepromatous leprosy.