Complement receptor 1 (CR1, CD35) association with susceptibility to leprosy.

BACKGROUND: Pathophysiological mechanisms are still incompletely understood for leprosy, an urgent public health issue in Brazil. Complement receptor 1 (CR1) binds complement fragments C3b/C4b deposited on mycobacteria, mediating its entrance in macrophages. We investigated CR1 polymorphisms, gene expression and soluble CR1 levels in a case-control study with Brazilian leprosy patients, aiming to understand the role of this receptor in differential susceptibility to the disease. METHODOLOGY: Nine polymorphisms were haplotyped by multiplex PCR-SSP in 213 leprosy patients (47% multibacillary) and 297 controls. mRNA levels were measured by qPCR and sCR1 by ELISA, in up to 80 samples. PRINCIPAL FINDINGS: Individuals with the most common recombinant haplotype harboring rs3849266*T in intron 21 and rs3737002*T in exon 26 (encoding p.1408Met of the York Yka+ antigen), presented twice higher susceptibility to leprosy (OR = 2.43, p = 0.017). Paucibacillary patients with these variants presented lower sCR1 levels, thus reducing the anti-inflammatory response (p = 0.040 and p = 0.046, respectively). Furthermore, the most ancient haplotype increased susceptibility to the multibacillary clinical form (OR = 3.04, p = 0.01) and presented the intronic rs12034383*G allele, which was associated with higher gene expression (p = 0.043), probably increasing internalization of the parasite. Furthermore, there was an inverse correlation between the levels of sCR1 and mannose-binding lectin (initiator molecule of the lectin pathway of complement, recognized by CR1) (R = -0.52, p = 0.007). CONCLUSIONS: The results lead us to suggest a regulatory role for CR1 polymorphisms on mRNA and sCR1 levels, with haplotype-specific effects increasing susceptibility to leprosy, probably by enhancing parasite phagocytosis and inflammation.

Perfil de auto-anticorpos em indios das tribos Kaingang e Guarani do Sul do Brasil / Autoantibody profile among Kaingang and Guarani Indians in southern Brazil

O presente estudo teve por objetivo investigar o perfil de auto-anticorpos em 241 amostras de sangue de 176 indios Kaingang 6 65 indios Guarani de tres populacoes das reservas indigenas do Rio das Cobras e Ivai, no Estado do Parana, regiao Sul do Brasil. Foram investigados os anticorpos antimusculo liso, antimitocondrias, antinucleares, anticelulas gastricas parietais e antimicrossomas de figado e rim, por metodo de imunofluorescencia indireta. Os resultados foram comparados com os de um grupo de 100 individuos sadios, pertencentes a populacao geral. Obteve-se uma positividade total de 9 por cento para a populacao indigena investigada e 4 por cento para os controles, com resultado significativo para prevalencia dos anticorpos antimusculo liso nas populacoes Kaingang e Guarani do Rio das Cobras (P= 0,03). E provavel que as praticas culturais envolvendo escarificacoes, tatuagens e processamento oral de alimentos, aliadas ao processo de aculturacao e maior convivio com populacoes nao indigenas, exponham os indios a doencas infecciosas anteriormente inexistentes entre os mesmos. Possiveis mecanismos de mimetismo molecular a antigenos virais ou bacterianos poderiam explicar a presenca desses auto-anticorpos nessas populacoes indigenas

This study investigated the autoantibody profile of 241 blood samples from 176 Kaingang and 65 Guarani Indians from three populations living on the Rio das Cobras and Ivaí reservations, in the state of Paraná, in southern Brazil. The presence of antimitochondrial, antismooth muscle, antinuclear, antiparietal cell, and anti-liver-kidney microsome antibodies was determined by indirect immunofluorescence. These results were compared with samples from 100 healthy Caucasian individuals from the general population of the state. Total positivity was 9% for the indigenous population and 4% for the control population. The prevalence of antismooth muscle antibodies was significantly higher among the Guarani and Kaingang individuals from the Rio das Cobras reservation (P = 0.03). It is likely that the increased exposure that these indigenous Brazilians have to infectious diseases that were previously unknown to them comes from more contact with nonnative populations, growing acculturation, and cultural practices that include scarification and tattooing. The presence of autoantibodies in these Brazilian Indians may be related to mechanisms of molecular mimicry with viral or bacterial antigens.

Perfil de auto-anticorpos em índios das tribos Kaingang e Guarani do Sul do Brasil / Autoantibody profile among Kaingang and Guarani Indians in southern Brazil

O presente estudo teve por objetivo investigar o perfil de auto-anticorpos em 241 amostras de sangue de 176 indios Kaingang 6 65 indios Guarani de tres populacoes das reservas indigenas do Rio das Cobras e Ivai, no Estado do Parana, regiao Sul do Brasil. Foram investigados os anticorpos antimusculo liso, antimitocondrias, antinucleares, anticelulas gastricas parietais e antimicrossomas de figado e rim, por metodo de imunofluorescencia indireta. Os resultados foram comparados com os de um grupo de 100 individuos sadios, pertencentes a populacao geral. Obteve-se uma positividade total de 9 por cento para a populacao indigena investigada e 4 por cento para os controles, com resultado significativo para prevalencia dos anticorpos antimusculo liso nas populacoes Kaingang e Guarani do Rio das Cobras (P= 0,03). E provavel que as praticas culturais envolvendo escarificacoes, tatuagens e processamento oral de alimentos, aliadas ao processo de aculturacao e maior convivio com populacoes nao indigenas, exponham os indios a doencas infecciosas anteriormente inexistentes entre os mesmos. Possiveis mecanismos de mimetismo molecular a antigenos virais ou bacterianos poderiam explicar a presenca desses auto-anticorpos nessas populacoes indigenas