Enfermedad celíaca y su patogenia / An update on the pathogenesis of celiac disease

Celiac disease (CD), with a 1 percent worldwide prevalence, is an enteropathy caused by an autoimmune reaction to gluten in genetically susceptible individuals, which codify for histocompatibility molecules HLA DQ-2/DQ-8. From the anatomical point of view, CD is characterized by intestinal villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis (IELs) and leukocyte infiltration of the lamina propriety. Patients achieve a complete clinical and endoscopic remission with a gluten free diet. However, symptoms and anatomical alterations recur when this protein is reintroduced in the diet. The pathogenic mechanisms in this disease are not yet well understood, but it is clear that genetic, environmental and immunological factors play a role. The latter are the focus of this review, since this is the only autoimmune disease whose precipitating factor for immunological tissue damage is known.

Estudo comparativo entre reação de Mitsuda e antígenos leucocitários humanos em pacientes hansenianos / Comparative study between the Mitsuda test and the human leukocyte antigens in leprosy patients

Neste estudo, propomos comparar o teste cutâneo de Mitsuda e os alelos HLA-DR2/HLA-DR3 e HLA-DQ1 relacionados com as formas clínicas da hanseníase em 176 pacientes (50 TT, 50 LL e 76 B). Os resultados obtidos não revelaram associação entre reação de Mitsuda e os alelos HLA nas formas clínicas isoladas; no entanto, quando analisados de acordo com a resposta ao teste de Mitsuda, associação significativa foi encontrada entre os pacientes Mitsuda negativos e HLA-DQ1 (p=0,002). Não foi observada associação entre reação de Mitsuda positiva e alelos HLA-DR2/DR3. Concluímos que existe importante participação do alelo HLA-DQ1 na ausência de resposta ao teste de Mitsuda. Sugerimos estudos mais específicos para este alelo.

In this study, we aimed to compare the Mitsuda skin test with the alleles HLA-DR2/HLA-DR3 and HLA-DQ1, in relation to the clinical forms of leprosy in 176 patients (50 TT, 50 LL and 76 B). The results obtained did not reveal any association between the Mitsuda reaction and the HLA alleles in the clinical forms isolated. However, when analyzed according to Mitsuda test response, a significant association was found between patients with negative Mitsuda reaction and HLA-DQ1 (p=0.002). No association was observed between positive Mitsuda reaction and the HLA-DR2/DR3 alleles. We concluded that the allele HLA-DQ1 has an important participation when there is no response to the Mitsuda test. We suggest that more specific studies should be developed on this allele.

Imunodiagnostico da leptospirose humana atraves do teste ELISA-IgM, empregando-se diferentes preparacoes antigenicas a partir de sorotipos prevalentes de Leptospira interrogans / Immunodiagnostic of human leptospirosis by ELISA-IgM, employing different antigenic preparations as from prevalent serovars of Leptospira interrogans

Realizou-se estudo comparativo de diferentes sorotipos de Leptospira interrogans utilizados na preparacao de antigenos empregados no teste ELISA, para a deteccao de anticorpos da classe IgM, em amostras de soro na fase precoce e tardia da leptospirose humana. Foram utilizados dez sorotipos, escolhidos entre os que apresentaram maior reatividade na soroaglutinacao microscopica (SAM), na cidade de Sao Paulo. Os cinco sorotipos que apresentaram melhores resultados individualmente no teste ELISA-IgM (canicola, hebdomadis, icterohaemorrhagiae, cynopteri e brasiliensis), foram tambem estudados em mistura antigenica. Os antigenos nao tratados apresentaram maior reatividade do que os antigenos tratados com Triton X-100 (4 por cento) a temperatura de 50§C, durante 4 horas. O teste ELISA-IgM empregando os sorotipos nao tratados, isoladamente, e em mistura antigenica, mostrou-se altamente sensivel, podendo ser empregado como teste de triagem para o diagnostico precoce da leptospirose humana. Outra aplicacao do teste e permitir a deteccao do inicio de situacoes epidemicas ou de surtos, possibilitando acionar medidas de vigilancia epidemiologica

Respondedores y no respondedores: su influencia en el trasplante renal de cadáver; estudio preliminar / Respondent and non-respondent patients: their influence on cadaver renal transplantation; preliminary study

Se estudiaron 99 pacientes con la insuficiencia renal crónica terminal en espera de trasplante renal, de los cuales fueron trasplantados 40 con riñón de cadáver. Se clasificó a estos pacientes en respondedores y no respondedores, según produjeron o no anticuerpos linfocito-tóxicos, frente al estímulo antigénico representado por las transfusiones sanguíneas. El 20% de los 99 pacientes se clasificó como no respondedores, el resto, como respondedores. Del grupo de 21 pacientes no respondedores, 11 fueron trasplantados y presentaron elevados porcentajes de supervivencia del injerto, 20 % mayor que el obtenido por los respondedores, con independencia del grado de compatibilidad HLA. En el grupo total de pacientes trasplantados, no se observó una influencia favorable de la compatibilización HLA entre donantes y receptor, así como tampoco en los pacientes clasificados como respondedores

Autoimmunogens, autoantigens, autoantibodies and autoimmune diseases: one-to-one or many-to-many relationships?

Cells with receptors capable of binding self-antigens constitute a normal component of the B cell repertoire; these specificities appear to be represented in low levels within the expressed antibody population. In autoimmune disease, this potential-actual repertoire is skewed in favor of exaggerated autoantibody expression. The clones or specificities affected are characteristic, even diagnostic of the particular disease, yet individuals express but a relatively small subset of this complexity. "Marker" autoantibodies may or may not be included, but autoantibodies more typical of other, related diseases are usually present. Certain specificities are clearly implicated in the pathogenesis of the corresponding disease; others contribute to- or exacerbate pre-existing pathological conditions, and still others appear at present as epiphenomena. Organ-/tissue-specific autoantibodies largely fall into the first or perhaps second categories; those associated with the systemic rheumatic diseases fit better into the latter or latter two categories. As we learn eventually more about these antibodies and the full spectra of autoantigens with which they react, many more may be found to exert more central roles in pathogenesis. The distortion of the expressed repertoire represents but one aspect of a far more complex set of pre-dispositions, conditions, stimuli, contributory factors and perhaps coincidences involved in the onset and perpetuation of the disease. The AAb arise within the context of a disease more pervasive than just the autoantibodies themselves, however, in certain diseases the subsequent autoimmune response may surpass all other variables to constitute the single most clinically significant factor. In attempting to account for these individual specificities and their disease associations, certain models seem applicable to selected autoantibodies but not to others. Even in these selected cases, the models remain speculative; in no case can we categorically state how the specificities arose. Non-specific activation may contribute to- and expand the expressed autoantibodies, but such mechanisms generally fall short in terms of adequately explaining the specificities of autoantibodies, the overlapping sets, the polyclonality of the response against single autoantigens or the specific disease associations. Despite this theoretical criticism, empirically, non-specific mechanisms have given rise to mixtures of autoantibodies which appear identical at least in terms of specificities to their spontaneous counterparts in various rheumatic diseases.(ABSTRACT TRUNCATED AT 400 WORDS)