RESUMO
Hemolytic uremic syndrome is a rare disease, frequently responsible for renal insufficiency in children. Recent findings have led to renewed interest in this pathology. The discovery of new gene mutations in the atypical form of HUS and the experimental data suggesting the involvement of the complement pathway in the typical form, open new perspectives for treatment. This review summarizes the current state of knowledge on both typical and atypical hemolytic uremic syndrome pathophysiology and examines new perspectives for treatment.
Assuntos
Síndrome Hemolítico-Urêmica/fisiopatologia , Animais , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções Bacterianas/complicações , Toxinas Bacterianas/efeitos adversos , Ensaios Clínicos como Assunto , Proteínas do Sistema Complemento/fisiologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/microbiologia , Previsões , Predisposição Genética para Doença , Síndrome Hemolítico-Urêmica/classificação , Síndrome Hemolítico-Urêmica/etiologia , Síndrome Hemolítico-Urêmica/genética , Síndrome Hemolítico-Urêmica/microbiologia , Síndrome Hemolítico-Urêmica/terapia , Humanos , Transplante de Rim , Transplante de Fígado , Camundongos , Papio , Plasma , Substitutos do Plasma , Toxina Shiga/efeitos adversos , Escherichia coli Shiga Toxigênica/imunologia , Escherichia coli Shiga Toxigênica/patogenicidade , Trombofilia/etiologia , Fator A de Crescimento do Endotélio Vascular/uso terapêuticoRESUMO
Calves become infected with Shiga toxin-producing Escherichia coli (STEC) early in life, which frequently results in long-term shedding of the zoonotic pathogen. Little is known about the animals' immunological status at the time of infection. We assessed the quantity and dynamics of maternal and acquired antibodies to Shiga toxins (Stx1 and Stx2), the principal STEC virulence factors, in a cohort of 27 calves. Fecal and serum samples were taken repeatedly from birth until the 24th week of age. Sera, milk, and colostrums of dams were also assessed. STEC shedding was confirmed by detection of stx in fecal cultures. Stx1- and Stx2-specific antibodies were quantified by Vero cell neutralization assay and further analyzed by immunoblotting. By the eighth week of age, 13 and 15 calves had at least one stx(1)-type and at least one stx(2)-type positive culture, respectively. Eleven calves had first positive cultures only past that age. Sera and colostrums of all dams and postcolostral sera of all newborn calves contained Stx1-specific antibodies. Calf serum titers decreased rapidly within the first 6 weeks of age. Only five calves showed Stx1-specific seroconversion. Maternal and acquired Stx1-specific antibodies were mainly directed against the StxA1 subunit. Sparse Stx2-specific titers were detectable in sera and colostrums of three dams and in postcolostral sera of their calves. None of the calves developed Stx2-specific seroconversion. The results indicate that under natural conditions of exposure, first STEC infections frequently coincide with an absence of maternal and acquired Stx-specific antibodies in the animals' sera.