Association of C4B deficiency (C4B*Q0) with erythema nodosum in leprosy

Abstract

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

The Association between Mannan‐Binding Lectin Gene Polymorphism and Clinical Leprosy: New Insight into an Old Paradigm

“…Furthermore, the results of the present study indicate that haplotypes/compound genotypes are more appropriate tools for MBL2-gene association studies, because the study of individual alleles could, to some extent, suggest an erroneous conclusion-for example, because the A allele is included within the defective haplotype LXPA. Although the development of ENL has been found to be associated with complement deficiency [37], the lack of association between MBL2 haplotypes/genotypes and the presence of ENL in multibacillary leprosy suggests that MBL polymorphism or deficiency plays no major role in the development of this reaction in patients with leprosy.…”

Rapid quantification of human complement component C4A and C4B genes by capillary gel electrophoresis

“…The same genetic variation was shown in Grave's disease [9], in polyarticular onset seronegative juvenile chronic arthritis [10], and in herpes gestation [11]. Nonexpressed C4B (C4B*Q0 allele) was reportedly associated with erythema nodosum [12] and IgA nephropathy [13].…”

Genetics of leprosy reactions: an overview

“…In a Brazilian sample, the C4B*Q0 allele was associated with risk to leprosy per se when cases were compared to healthy controls (p = 2.7 10 -5 ). Interestingly, the C4B*Q0 allele frequency was significantly higher among T2R cases (22 individuals) when compared with the LL patients who had no reaction (6) (p = 0.006) (de Messias et al 1993). These findings suggest that the complement system may affect both the phagocytosis during the reactivation/exacerbation of the inflammatory response in T2R and the stimulation of cellular immune responses, possibly through IP-10-related pathways.…”