SUMMARYA considerable number of studies have postulated significant associations between susceptibility to the different clinical manifestations of leprosy and the MHC, In this investigation, the association between the MHC class III complement proieins C2, BF, C4A and C4B and leprosy in a patient population of Southern Brazil was studied. A total of 109 non-related leprosy patients was investigated; 73 presented wilh lepromatous leprosy (LL), 46 of Ihem 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 lo their ethnic and geographical origin, C2, BF, C4A and C4B allotypes were determined by slandard technologies including Western blots for C2 and C4 variant alleles wilh monoclonal and polyclonal antibodies. Non-expressed ('silent') C4 alleles in hemizygously deficient individuals were estimated semiquantitatively on the basis ofthe C4A and C4B isolype ratio and by the M ASC ('minimal chi-square') method. The results showed a significantly elevated presence ofthe non-expressed C4B allele (C4B*Q0) in the LL and ENL patient groups in comparison with the controls. The most signifieant difference was observed in the ENL group when compared with the controls. In addition, all patients who were homozygously C4B-deficient had ENL, and most of them had the BF*F1 allele. The comparison between LL patients with and without ENL also showed a statistically significant difference in the presence of C4B*Q0, indieating thai C4B deficiency itself is associated with ENL. The relative risk of LL patients with the C4B*Q0 allele suffering from ENL was 5 3 compared with LL palients without C4B*Q0, Since immune complexes (IC) are considered to be the palhogeniccauseof ENL, our findings indicate thai C4B deficieney may play an important role in the abnormal immune response against Myeobaeterium leprae and in the lack of IC clearance, leading to ENL reactions. Individuals wilh this allele seem to be at a higher risk of developing pathologieal immune reactivity in lepromatous leprosy.Keywords eomplement genetics major histocompatibility complex C2 BF C4 lepromatous leprosy erythema nodosum leprosum

A genetic influence of the major histocompatibility complex (MHC) on the susceptibility and the development of the different clinical forms of paracoccidioidomycosis (PCM) has been postulated. In the present investigation allotypes of MHC-coded class III gene products (complement components C2, BF, C4A, and B) were determined in 69 Brazilian PCM patients and 225 healthy control individuals matched for ethnic and geographic origin. The frequency of the non-expressed C4B allele (C4B*Q0) was significantly elevated in comparison to the controls (p < 0.01; Fisher’s exact test). Three out of 69 patients had a complete C4B deficiency as against 2 among 223 control individuals. The C4A *Q0 allele was also more frequent in the patients. Other C4 alleles were not seen to differ between the two groups. The analysis of BF allotypes showed a non-significant predominance of the rarer allele BF*S07 in the patients, whereas no difference in the distribution of C2 alleles was seen. The data on MHC class III association may support the hypothesis of immune response modulation in PCM and suggest a functional genetic role of complement action against the fungus and in the outcome of PCM infection. We conclude that MHC class III products, especially C4B*Q0, are associated with chronic uni- or multifocal PCM and may influence the course of the infection.