Maria E. Moraes

Susceptibility to leprosy is associated with PARK2 and PACRG

Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year. It has long been thought that leprosy has a strong genetic component, and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25–q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5′ regulatory region shared by the Parkinsons disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy.

Desmoglein-1–specific T lymphocytes from patients with endemic pemphigus foliaceus (fogo selvagem)

Fogo selvagem (FS), the endemic form of pemphigus foliaceus, is a cutaneous autoimmune disease characterized by subcorneal blistering of the epidermis and the production of autoantibodies against the desmosomal antigen desmoglein-1 (Dsg1). Previously, we showed that mice injected with autoantibodies from FS patients develop a skin disease that reproduces the clinical, histological, and immunological features of FS, indicating that autoantibodies play an essential role in the development of this disease. The purpose of this study was to characterize the autoimmune T-cell response associated with FS. We provide here the first evidence, to our knowledge, that the great majority of FS patients have circulating T lymphocytes that specifically proliferate in response to the extracellular domain of Dsg1. Long-term T cells developed from these patients also responded to Dsg1, and this antigen-specific response was shown to be restricted to HLA-DR molecules. These Dsg1-reactive FS T cells exhibited a CD4-positive memory T-cell phenotype and produced a T helper 2-like cytokine profile. These findings represent the initial steps in defining the role of T cells in FS autoimmunity.

Interleukin–10 promoter haplotypes are differently distributed in the Brazilian versus the Dutch population

Abstract.The frequency of five different single nucleotide polymorphisms of the promoter interleukin-10 (IL–10) gene (–3575, –2849, 2763, –1082, –819) was compared between two healthy populations, one originating from the Netherlands and one from Rio de Janeiro, Brazil. A total of 321 Caucasian Dutch individuals and 293 Brazilians, grouped as Afro–Brazilians and Euro–Brazilians, were genotyped using PCR–RFLP. The frequencies of the genotypes in the Brazilian population were different (P<0.05) from the frequencies in the Dutch population in all but one (–2763) genotype. The comparison of genotype frequencies between Afro– and Euro–Brazilians did not demonstrate any differences. The haplotype combination of the most-distant three polymorphisms showed strong linkage disequilibrium. All eight possible combinations were observed in Brazilians, but only seven in Dutch Caucasians. The haplotype frequencies were also significantly different between Brazilians when compared with Dutch and also between Euro–Brazilians and Dutch. No differences were observed in haplotype frequencies between Afro–Brazilians and Euro–Brazilians. The −3575T/–2849G/–2763C is more frequent, while the AAA haplotype was much less represented in the Brazilian than in the Dutch population. The haplotype TAC, which was described in African–Americans, was observed only in Brazilians, almost exclusively among those of European origin. The results corroborate the data indicating that the Brazilian population exhibits a genetic admixture of Africans, Europeans, and Amerindians, and the data may serve as a background for clinical and immunological studies involving the IL-10 locus.

Manejo agrícola no refúgio de vida silvestre de una: agroflorestas como uma perspectiva de conservação

RESUMO – Este estudo investiga os tipos de manejo e o perfil socioeconomico relacionado a estes, nas propriedades rurais do Refugio de Vida Silvestre de Una. Tem-se como pressuposto de que as agroflorestas sucessionais sao as mais favoraveis para conservacao do bioma Mata Atlântica, inclusive na escala de paisagem. Portanto, objetiva-se conhecer os aspectos socioeconomicos associados a adocao de um tipo de manejo e sua insercao na paisagem. Para tanto, foram realizadas entrevistas em 73 propriedades, entre janeiro e maio de 2011. Os dados sobre os agrossistemas foram classificados em tipos de manejo: convencional, tradicional, orgânico e agroflorestal. Os resultados apontaram a predominância do tipo de manejo tradicional entre as propriedades. O perfil socioeconomico encontrado e compativel com as caracteristicas do tipo de manejo predominante, o tradicional. Observaram-se no manejo tradicional: maior contribuicao da mao de obra familiar e menor ocorrencia de fonte de renda proveniente de trabalho rural para terceiros. A capacitacao para atividade agricola foi a unica caracteristica socioeconomica que apresentou maior importância para o manejo agroflorestal. Na paisagem, os resultados apontaram para a necessidade de adequacao das praticas utilizadas nos agroecossistemas tradicionais aos objetivos da conservacao do bioma, pois 39% das propriedades estao a uma distância de 350 m dos fragmentos, considerada maxima para que ocorra a conectividade estrutural, e possuem esse tipo de manejo.

Infecção experimental por Mycoplasma gallisepticum e Escherichia coli em perus

Mycoplasma gallisepticum (MG) causes infectious sinusitis in turkeys, and is commonly associated with Escherichia coli. The objective of this study was to develop in turkeys an experimental model for infectious sinusitis. Two hundred and fifty male turkeys of Nicholas breed (Aviagen®) were divided into negative control group and challenged, animals were housed until 42 days old. The birds were inoculated in the first day of age with the MG vaccine (F-VAX ® Schering Plough) and on day 21 with E. coli. We analyzed the mortality, clinical signs and lesions in air sacs, liver and heart. The results showed that the vaccine against Mycoplasma gallisepticum (MG-F) is pathogenic for turkeys and that the experiment was able to simulate natural infection with MG and E. coli.

92-P : UNUSUAL HLA-DRB1-DQA1-DQB1 ASSOCIATION FOUND IN AN EXTENDED HAPLOTYPE IN SEVEN BRAZILIAN INDIVIDUALS

Aim To report an unusual association of HLA-DRB1∗11:01- HLA-DQA1∗05:05-HLA-DQB1∗04:02 found in seven Brazilian individuals. Methods HLA analysis was performed in 14213 randomly selected individuals (7162 patients and 7051 normal donors) from Rio de Janeiro and Sao Paulo - Brazil. The great majority of the HLA typing was performed by intermediate resolution methodologies by polymerase chain reaction with sequence specific oligonucleotides (PCR-SSO) using commercial kits (Lab-Type SSO; One Lambda inc., Canoga Park , CA) and /or rSSO – InnoLiPA (Innogenetics, NV, Ghent, Belgium). High resolution typings were performed by PCR-SBT (AlleleSEQR-HLA-SBT Reagents, Celera, USA). Results In Brazilians, as reported in other ethnic groups, HLA-DRB1∗11 is found associated with different HLA-DQB1 alleles: HLA-DQB1∗02:01, 03:01, 03:02, 03:03, 03:04, 03:19, 05:01, 05:02, 06:02, 06:11 and 06:03. The most frequent association is HLA-DRB1∗11:01- HLA-DQB1∗03:01, mainly in Brazilian Caucasoid. An interesting, unusual and not yet reported HLA-DRB1∗11:01 association was found with HLA-DQA1∗05:05, HLA-DQB1∗04:02 in 4 of the patients and in 3 of the normal donors. This HLA-DRB1-DQA1-DQB1 association, shares an extended haplotype: HLA-A∗02:01, HLA-C∗14:02, HLA-B∗51:01, HLA-DRB1∗11:01, HLA-DQA1∗05:05, HLA-DQB1∗04:02. This data was confirmed by segregation analysis, performed in a parallel study, in one of these patient’s family. Conclusions The identification of this rare extended haplotype, shown here for the first time in Brazilians, and so far not reported in other populations, is a good example of our ethnic diversity and may be an important data to take into consideration for recruitment and matching process of unrelated donors for haematopoietic stem cell transplantation.