Diversidade genética do sistema HLA em Portugal, Cabo Verde e Guiné-Bissau

O polimorfismo dos genes HLA-A, HLA-B e HLA-DRB1 foi estudado em três populações Portuguesas (Portugal continental, Madeira e Açores) e em duas Africanas (Guiné-Bissau e Cabo Verde). Os dados em alta resolução, obtidos por sequenciação (SBT), foram comparados com a caracterização efectuada pelo método SSOP revelando 4,6% de incongruências entre os resultados destes dois métodos. Os alelos mais frequentes em cada um dos loci foram: HLA-A*0201 em todas as populações (13,5-26%); HLA-B*5101 em Portugal continental (12%, o mesmo para o B*440301), Madeira (9,7%) e Açores (9,8%) e B*350101 na Guiné-Bissau (14,4%) e Cabo Verde (13,2%); HLADRB1*0701 em Portugal continental (15%), Madeira (15,7%) e Açores (18,3%), DRB1*1304 na Guiné-Bissau (19,6%) e DRB1*110101 em Cabo Verde (10,1%). Os haplotipos 3-loci mais predominantes em cada população foram: A*020101-B*440301-DRB1*070101 em Portugal continental (3,1%), A*020101-B*510101- DRB1*130101 na Madeira (2,7%), A*2902-B*4403-DRB1*0701 nos Açores (2,4%), A*2301-B*1503-DRB1*110101 na Guiné-Bissau (4,6%) e A*3002-B*350101-DRB1*1001 em Cabo Verde (2,8%). O presente trabalho revela que a população continental Portuguesa tem sido influenciada geneticamente por Europeus e Norte Africanos devido a várias imigrações históricas. O Norte de Portugal parece concentrar, provavelmente devido à pressão da expansão Árabe, um antigo pool genético originado pela influência milenar de Europeus e Norte Africanos. Os dados obtidos nos genes do sistema HLA corroboram as fontes históricas que confirmam que o povoamento dos Açores teve o contributo de outros Europeus, essencialmente Flamengos, para além dos Portugueses. As frequências alélicas e haplotípicas neste arquipélago não apresentam uma distribuição homogénea entre as ilhas do grupo Oriental e Central. O grupo Central revela uma influência clara daEuropa Central e uma muito menor afinidade a Portugal continental. As frequências alélicas e haplotípicas mostram que a ilha da Madeira foi povoada por Europeus, a maioria Portugueses, mas também por sub-Saharianos devido ao comércio de escravos. Cabo Verde não é uma população tipicamente sub-Sahariana pois revela uma importante influência genética Europeia, para além da base genética Africana. A análise dos haplotipos e dendrogramas mostram uma influência genética Caucasiana no actual pool genético Cabo-Verdiano. Os dendrogramas e a análise das coordenadas principais mostram que os Guineenses são mais semelhantes aos Norte Africanos do que qualquer outra população sub-Sahariana já estudada ao nível do sistema HLA, provavelmente devido a contactos históricos com outros povos, nomeadamente Árabes do Este Africano e Berberes.

Polimorfismo do alelo HLA-B27 no desenvolvimento das espondilartropatias

A associação da molécula HLA-B27 com a espondilite anquilosante (AS) e outras espondilartropatias (SpA), permanece como uma das mais fortes verificada entre moléculas HLA e doenças humanas. Desde que foi descrita, em 1973, tem sido alvo de intensa investigação na tentativa de compreender o mecanismo patogénico que lhe está subjacente. Este artigo tem como objectivo fazer uma revisão dos conhecimentos actuais relativos à estrutura e polimorfismo da molécula HLA-B27, bem como descrever os modelos propostos para explicar o seu papel no desenvolvimento das espondilartropatias.

Leishmania (Viannia) shawi purified antigens confer protection against murine cutaneous leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação da expressão das moléculas HLA de classe I não clássicas HLA-G E HLA-E em espécimes gástricas de pacientes acometidos com a bactéria Helicobacter Pylori

The expression of human leukocyte antigen G (HLA-G) and human leukocyte antigen E (HLA-E) in physiological and pathological processes remains unknown, it is believed that these molecules play a fundamental role in the establishment and maintenance of immune tolerance by inhibiting the functions of immunocompetent cells. In literature we found no published study involving the bacterium Helicobacter pylori (H. pylori) with expression of HLA-G and HLA-E. The objective this study is investigated the expression of this protein in gastric biopsies of patients with the bacterium H. pylori. Sixty-four biopsies of the patients with diagnosis of infection by H. pylori were evaluated to expression of HLA-G and HLA-E. The samples were stratified according to the presence of carcinoma or peptic ulcers. Patients without H. pylori were used to control. To investigate the expression of this protein were used immunohistochemistry technique with monoclonal antibody anti-HLA-G and anti-HLA-E. Other criteria such as analysis of the inflammatory infiltrate (hematoxylin-eosin) and identification of H. pylori (Giemsa) were analyzed. We detected HLA-G and HLA-E molecules in the most samples containing ulcer and gastric carcinoma. In negative control group was not detected the presence of HLA-G and HLA-E. The presence of H. pylori seems modulate the expression of HLA-G and HLA-E, favoring the evolution of infection, giving different degrees of gastric lesion in epithelium of these patients

Humoral immune response of water buffalo monitored with three different antigens of Toxocara vitulorum

Humoral immune response of water buffalo naturally infected with Toxocara vitulorum was monitored using three different antigens of this parasite in serum and colostrum of buffalo cows and calves. Soluble extract (Ex) and excretory/secretory (ES) larval antigens and perienteric fluid antigen (Pe) of adult T vitulorum were used to measure the antibody levels by an indirect ELISA. Serum of 7-12 buffalo cows for the first 365 days and colostrum of the same number of buffalo cows for the first 60 days of parturition, and serum of 8-10 buffalo calves for the first 365 days afterbirth were assayed. The ELISA detected antibodies against all three T vitulorum antigens in the colostrum and serum of 100% of buffalo cows and calves examined. The highest antibody levels against Ex, ES and Pe antigens were detected in the buffalo cow sera during the perinatal period and were maintained at high levels through 300 days after parturition. on the other hand, colostrum antibody concentrations of all three antigens were highest on the first day post-parturition, but decreased sharply during the first 15 days. Concomitantly to the monitoring of immune response, the parasitic status of the calves was also evaluated. In calves, antibodies passively acquired were at the highest concentrations 24 h after birth and remained at high levels until 45 days coincidentally with the peak of T vitulorum infection. The rejection of the worms by the calves occurred simultaneously with the decline of antibody levels, which reached their lowest levels between 76 and 150 days. Thereafter, probably because of the presence of adults/larvae stimulation, the calves acquired active immunity and the antibodies started to increase slightly in the serum and plateaued between the days 211 and 365. All three antigens were detected by the serum antibodies of buffalo calves; however, the concentration of anti-Pe antibody was higher than anti-EX and anti-ES, particularly after 90 days of age. By conclusion, the buffalo cows develop immunity and keep high levels of antibodies against T vitulorum-Ex, ES and Pe antigens and these antibodies are transferred to their calves through the colostrum. This passively acquired immunity does not protect the calves against the acquisition of the infection, but these antibodies, passively or actively acquired, may have an important role during worm rejection by the calves and prevention of intestinal reinfection. (C) 2004 Elsevier B.V. All rights reserved.

Dendritic cell are able to differentially recognize Sporothrix schenckii antigens and promote Th1/Th17 response in vitro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

TNFa-e microsatellite, HLA-DRB1 and-DQB1 alleles and haplotypes in Brazilian patients presenting recently diagnosed type 1 diabetes mellitus

TNF microsatellite and HLA class II polymorphisms were studied in 28 recently diagnosed Brazilian patients presenting type 1 diabetes mellitus (T1DM) and in 120 healthy controls. TNFa-e and HLA-DRB1/DQB1 alleles were identified using sets of sequence-specific primers. Compared to controls, the DRB1* 03 and DQBI*02 allele groups, TNFa1 allele, and the TNFa4-b5-c1-d4-e3 and TNFa10-b5-c1-d4-e3 haplotypes were overrepresented in patients. TNF microsatellite together with HLA polymorphisms is associated with type 1 diabetes in Brazilian patients, corroborating the participation of the MHC genes in disease susceptibility.

Production of Trichophyton mentagrophytes antigens and their characterization in mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Taenia saginata: Production and characterization of monoclonal antibodies against Taenia saginata metacestode antigens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Detection of antibody to Toxocara vitulorum perieneteric fluid antigens (Pe) in the colostrum and serum of buffalo calves and cows by Western blotting

Toxocara vitulorum, a nematode parasite in the small intestine of cattle and water buffaloes, causes high morbidity and mortality of 1-3 months old buffalo calves. This research evaluated the specific perieneteric antigens (Pe) reactivity of anti-T. vitulorum-Pe antibody (Tv-Pe-Ab) in both immune sera and colostrum from buffalo cows immediately post-partum from buffalo cows. The presence of Tv-Pe-Ab in sera of buffalo newborn calves was also examined at 1 day before and after suckling the colostrum as well as in sera from naturally infected calves at the beginning and peak of the maximum infection and then again during the period of rejection and post-rejection of the parasite. Pe antigens were characterized for Tv-Pe-Ab by SDS-PAGE and Western blot (WB). The SDS-PAGE showed that Pe contained nine protein bands (11, 14, 31, 38, 58, 76, 88,112 and 165 kDa). All Pe bands were recognized by Tv-Pe-Ab in sera and colostrum of buffalo cows. Only the serum antibodies of buffalo calves at 1 day of age after suckling the colostrum and during the beginning of T. vitulorum infection recognized Pe antigen's nine bands. In contrast, serum antibodies from 1-day-old buffalo calves, taken before suckling colostrum, did not react with any protein band. In suckling calves, which reached peak egg output, rejection and post-rejection stages of the infection, serum Tv-Pe-Ab reactivity with lower molecular weight protein bands (11-76 kDa) was lost and only reactivity with the Pe protein bands of higher molecular weight (88, 112 and 165 kDa) remained. (c) 2005 Elsevier B.V. All rights reserved.

Allelic Frequencies of HPA-1 to 5 Human Platelet Antigens in Patients Infected With Hepatitis C Virus

Studies have suggested that hepatitis C virus (HCV) may infect not only hepatocytes but may also be carried by platelets. Platelets express more than 20 polymorphic antigenic determinants on their surface, which are called human platelet antigens (HPA), To determine the allele frequency of the HPA-1 to -5 in patients infected with HCV, blood samples were collected from 257 blood donors for the control group and from 191 patients infected with HCV. DNA was isolated and amplified for genes HPA-1 to -4 using PCR Sequence Specific Primers (PCR-SSP) and HPA-5 using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP). The allelic and genotypic frequency of HPA-5a in patients infected with HCV was found to be significantly lower(P < 0.05) than in the controls, and HPA-5b from patients infected with HCV was significantly higher (P < 0.05) than in controls. The increase in HPA5b allelic frequency in HCV infection may indicate a possible association between HCV infection and HPAs. J. Med. Virol. 81:757-759, 2009. (C) 2009 Wiley-Liss, Inc.