RESUMO
BLyS and APRIL have similar but distinct biological roles, mediated through two known TNF receptor family members, TACI and BCMA. We show that mice treated with TACI-Ig and TACI-Ig transgenic mice have fewer transitional T2 and mature B cells and reduced levels of circulating immunoglobulin. TACI-Ig treatment inhibits both the production of collagen-specific Abs and the progression of disease in a mouse model of rheumatoid arthritis. In BLyS-deficient mice, B cell development is blocked at the transitional T1 stage such that virtually no mature B cells are present, while B-1 cell numbers are relatively normal. These findings further elucidate the roles of BLyS and APRIL in modulating B cell development and suggest that BLyS is required for the development of most but not all mature B cell populations found in the periphery.
Assuntos
Doenças Autoimunes/etiologia , Linfócitos B/imunologia , Proteínas de Membrana , Receptores do Fator de Necrose Tumoral/metabolismo , Animais , Formação de Anticorpos , Artrite Reumatoide/etiologia , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Receptor do Fator Ativador de Células B , Linfócitos B/classificação , Diferenciação Celular , Linhagem da Célula , Colágeno/imunologia , Homozigoto , Imunoglobulinas/sangue , Camundongos , Camundongos Transgênicos , Fenótipo , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/imunologia , Proteína Transmembrana Ativadora e Interagente do CAMLRESUMO
In the B19 VP2 molecule an immunodominant heptapeptide epitope has been detected, recently for which IgG antibodies are synthesized exclusively in the acute phase of B19 infection. Using this acute-phase-specific epitope (KYVTGIN) a 2(nd)-generation epitope-type EIA was developed, which compares serum IgG activity for native VP2 capsids exhibiting conformational VP2 epitopes with IgG activity for the KYVTGIN epitope. In this study the diagnostic performance (clinical sensitivity and specificity) of the 1st and 2nd-generation epitope-type EIAs and of a peptide-based EIA utilising as antigen the KYVTGIN epitope alone was assessed in comparison with various high-quality IgM- and IgG- based B19 assays. Serum samples from 489 patients with B19-related symptoms and asymptomatic controls from three countries were studied. Among 323 patients with B19-IgG, 20% were diagnosed as acute infection, 73% had past immunity and 7% were not classified due to contradictory results among the different assays. The unclassified samples were explored for viral strain diversity by PCR and DNA sequencing but all sequences obtained were B19-like with variance of only a few per cent. The 2nd-generation epitope-type EIA had a diagnostic sensitivity of 98% and a diagnostic specificity of 94%. In combination with conventional approaches, the epitope-type assays increase greatly the accuracy of B19 serodiagnosis.
Assuntos
Anticorpos Antivirais/análise , Proteínas do Capsídeo , Capsídeo/imunologia , Imunoglobulina G/análise , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/imunologia , Parvovirus B19 Humano/imunologia , Kit de Reagentes para Diagnóstico , Doença Aguda , Capsídeo/genética , Genótipo , Humanos , Epitopos Imunodominantes , Técnicas Imunoenzimáticas/métodos , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/classificação , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/isolamento & purificação , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Alinhamento de Sequência , Análise de Sequência de DNA , Testes Sorológicos , EstreptavidinaRESUMO
In 1994 the first human parvovirus B19 (B19) epidemic to be documented in Denmark was recorded from February 2 to September 30. In total, 10,333 serum samples were tested for specific B19 IgM and IgG antibodies, using IDEIA Parvovirus B19 IgM and IgG kits. The prevalence of B19 IgM positivity was 11% for the whole period and 29% at the peak of the epidemic in week 14, declining from week 39 and onwards to 1-3%. The prevalence of B19 IgG (IgM-negative samples) was 60%, indicating an earlier infection, and the same for men and women. The gender distribution of tested patients was the same at the beginning of the epidemic as at the end of the epidemic and a year after its peak, i.e. 86% of samples were from women and only 14% from men. Age distribution for women was the same for the three periods (median age 34 years). For men the median age was 32 years, 39 years and 31 years, respectively. Only a few samples from children were tested. No change in test pattern was observed during the three periods. Approximately 75% of all samples tested were from women of childbearing age (18-45 years old), suggesting a fear of fetal complications in an actual or future pregnancy, rather than a serological verification of clinical symptoms. From the sparse clinical information that accompanied the serum sample we were not able to demonstrate that women were more likely than men to have a symptomatic B19 infection. With reservations we estimate that 14% of adverse pregnancy outcome is correlated with a B19 infection.
Assuntos
Infecções por Parvoviridae/epidemiologia , Parvovirus B19 Humano , Adolescente , Adulto , Distribuição por Idade , Idoso , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Masculino , Pessoa de Meia-Idade , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/imunologia , Parvovirus B19 Humano/imunologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/imunologia , Prevalência , Estudos Retrospectivos , Estudos Soroepidemiológicos , Distribuição por SexoRESUMO
By means of intra- and intermorph crosses it has been shown that the distyly in Anchusa officinalis L. is governed by a single diallelic locus with dominance. Presence of the dominant allele is reflected in the short-styled morph, while homozygous recessives become long-styled. Most of the short-styled plants are heterozygous, but homozygotes have been found among the raised progeny resulting from crossings. Diallel crosses have revealed that at least two incompatibility loci must exist. These and the morphological locus segregate independently. The type of incompatibility system is as yet unknown, though the great frequency of non-reciprocal incompatibility points to a sporophytic system.
RESUMO
A serious side reaction in the peptide synthesis on the Merrifield resin was observed during attempts to synthesize the TMV fragment, Asn-Pro-Thr-Thr-Ala (101--105). The side reaction is consistent with N-alkylation of the amino groups by the residual chloromethyl groups on the resin, which lowers the total yield and complicates evaluation of monitoring data during the synthesis. It is shown that several amino acids can be N-alkylated in different positions in the peptide chain and in different solvents. The extent of N-alkylation is in some cases 50%.