RESUMO
A 1-yr-old Japanese male infant developed hepatitis-associated aplastic anemia (AA), and anti-thymocyte globulin (ATG) plus cyclosporine A (CsA) was administered without any appreciable effects. Laboratory examination of the patient's serum obtained before therapy revealed various autoantibodies, such as PA-IgG, anti-platelets, anti-single-stranded DNA (ssDNA), and anti-double-stranded DNA (dsDNA) antibodies (Abs) in addition to anti-DRS-1 Abs and anti-moesin Abs, both of which are known to be detectable in approximately 40% of all patients presenting with AA. He was therefore treated with 17.5 mg/kg/d rituximab 5.5 months after ATG/CsA therapy. The same rituximab therapy was repeated three times once a month thereafter. His neutrophil counts started to increase 50 d after the first rituximab therapy and he achieved a complete remission at 16 months after the last rituximab administration. All of the autoantibodies including anti-ssDNA, dsDNA, DRS-1, and moesin became undetectable when he attained the remission. Anti-CD20 monoclonal antibody therapy may be effective in a subset of patients with AA characterized by the presence of autoantibodies.
Assuntos
Anemia Aplástica/imunologia , Anemia Aplástica/terapia , Anticorpos Monoclonais Murinos/uso terapêutico , Autoanticorpos/sangue , Anemia Aplástica/patologia , Anticorpos Antinucleares/sangue , Soro Antilinfocitário/uso terapêutico , Biomarcadores/sangue , Medula Óssea/patologia , Isomerases de Ligação Dupla Carbono-Carbono/imunologia , Ciclosporina/uso terapêutico , Dodecenoil-CoA Isomerase , Humanos , Lactente , Masculino , Proteínas dos Microfilamentos/imunologia , Indução de Remissão , Rituximab , Linfócitos T/imunologiaAssuntos
Anemia Aplástica/diagnóstico , Anemia Aplástica/imunologia , Autoanticorpos/sangue , Isomerases de Ligação Dupla Carbono-Carbono/imunologia , Proteínas dos Microfilamentos/imunologia , Anemia Aplástica/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Autoanticorpos/uso terapêutico , Biomarcadores/sangue , Dodecenoil-CoA Isomerase , Ensaio de Imunoadsorção Enzimática , Humanos , Espectrometria de Massas/métodos , RituximabRESUMO
High-throughput studies to determine differential immune (humoral) response to diseases are becoming of increasing interest because the information they provide can help in early diagnosis as well as monitoring of therapeutics. Protein microarrays are a high-throughput and convenient technology that can be applied to the study of the humoral response. Proteins can be arrayed on slides and then probed with serum from different classes of patients to observe differences that may exist among autoantibodies that reflect differences in disease states. However, such studies may be difficult to interpret due to the weak overall signal response of such protein microarrays. We propose that this weak signal response is due to the physical positioning of the disease proteins that renders them sterically hindered from binding partners in the serum. In this study, we hypothesize that reducing the complexity and size of the disease proteins by chemical digestion using cyanogen bromide (CNBr) may enhance the overall signal from the humoral response and facilitate visualization of disease-specific responses in various classes of serum. A modified protein microarray methodology using CNBr digestion is presented here. The new workflow was applied to a set of 10 serum samples from healthy subjects, 10 from patients with chronic pancreatitis and 10 from patients diagnosed with pancreatic cancer and the results were compared to results obtained in the absence of CNBr digestion. CNBr digestion allowed the identification of 10 additional autoantibodies that responded to serum, 5 of which were unique to pancreatitis and cancer sera. This new methodology may increase the sensitivity of microarray studies measuring autoantibodies in serum.