Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG

Rheumatoid arthritis (RA) is a widely prevalent (1-3%) chronic systemic disease thought to have an autoimmune component; both humoral and cellular mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin, implying that this is both the 'antibody' (rheumatoid factor [RF]) and the 'antigen' (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (C gamma 2) domains of IgG. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of approximately 1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a 'shift' in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.     

Genes for the major protein antigens of the leprosy parasite Mycobacterium leprae

Leprosy, a chronic infectious disease afflicting between 10 and 15 million people, is caused by the obligate intracellular parasite Mycobacterium leprae. Although M. leprae was the first identified bacterial pathogen of man, basic biochemical, immunological, diagnostic and therapeutic investigations have been severely limited because it remains one of the few human pathogens that have not been cultured in vitro. An M. leprae recombinant DNA expression library was constructed to provide a source of genes encoding proteins relevant for such studies. Monoclonal antibodies directed against M. leprae specific antigens have been used to isolate the genes encoding the five most immunogenic protein antigens of the leprosy bacillus. We report here that M. leprae specific epitopes recognized by all of 13 monoclonal antibodies tested were produced by recombinant phage in Escherichia coli.     

Distribution of some similarity coefficients for dyadic binary data in the case of associated attributes

Parameters are derived of distributions of three coefficients of similarity between pairs (dyads) of operational taxonomic units for multivariate binary data (presence/absence of attributes) under statistical independence. These are applied to test independence for dyadic data. Association among attributes within operational taxonomic units is allowed. It is also permissible for the two units in the dyad to be drawn from different populations having different presence probabilities of attributes. The variance of the distribution of the similarity coefficients under statistical independence is shown to be relatively large in many empirical situations. This result implies that the practical interpretation of these coefficients requires much care. An application using the Jaccard index is given for the assessment of consensus between psychotherapists and their clients.

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La distribution des coefficients de similarité pour les données binaires et les attributs associés

Résumé Les paramètres de la distribution de trois coefficients de similarité entre paires d'éléments taxinomiques opérationels de données multivariables binaires (présence/absence) ont été dérivés dans l'hypothèse d'indépendance statistique. Ces paramètres sont utilisés dans un test d'indépendance pour les données dyadiques. L'existence est autorisée, dans la population d'éléments, d'une association entre plusieurs attributs. Il est également permis que les deux éléments de la dyade soient tirés de deux populations différentes, ayant différentes probabilit és quant à la présence des attributs. Dans beaucoup de situations empiriques, la variance des coefficients de similarité peut être relativement élevée dans le cas d'indépendance statistique. Par conséquence, ces coefficients doivent être interprétés avec précaution. Un exemple est donné pour le coefficient de Jaccard, qui a été employé dans une recherche sur la concordance entre des psychothérapeutes et leurs clients.

     

Sm2Fe17化合物中Ga替代效应的理论分析

用单离子模型计算了Ｓｍ２Ｆｅ１７－ｘＧａｘ中的晶场，给出了晶场系数随Ｇａ含量的变化关系。在晶场和交换作用近似下，计算了体系的自由能随Ｇａ含量和温度的变化关系，用最小二乘法拟合自由能给出各向异性常数Ｋ，Ｋ２从而得到各向异性场Ｂａ。计算结果与实验中的规律基本符合。     

Estimation and Prediction for Stochastic Blockmodels for Graphs with Latent Block Structure

a posteriori blockmodeling for graphs is proposed. The model assumes that the vertices of the graph are partitioned into two unknown blocks and that the probability of an edge between two vertices depends only on the blocks to which they belong. Statistical procedures are derived for estimating the probabilities of edges and for predicting the block structure from observations of the edge pattern only. ML estimators can be computed using the EM algorithm, but this strategy is practical only for small graphs. A Bayesian estimator, based on the Gibbs sampling, is proposed. This estimator is practical also for large graphs. When ML estimators are used, the block structure can be predicted based on predictive likelihood. When Gibbs sampling is used, the block structure can be predicted from posterior predictive probabilities. A side result is that when the number of vertices tends to infinity while the probabilities remain constant, the block structure can be recovered correctly with probability tending to 1.     

Activated human eosinophils generate SRS-A leukotrienes following IgG-dependent stimulation

Eosinophils, a class of granular leukocytes, are prominent in many inflammatory processes, particularly in asthma, certain allergic diseases and during infections with helminthic parasites. Following incubation with the Ca ionophore A23187 (refs 1-4) (a non-physiological agent which circumvents membrane calcium-gating mechanisms), eosinophils generate large amounts of sulphidopeptide leukotrienes, potent inducers of smooth muscle constriction and mucus production. These are now known to represent the activity previously termed 'slow-reacting substance of anaphylaxis' (SRS-A) but attempts to identify a physiological stimulus for SRS-A production by eosinophils have so far been unsuccessful. The cells contain recognized receptors for IgG (Fc) and it is known that they adhere to, and can be activated by, contact with the surface of large organisms such as helminthic larvae. We show here that eosinophils, particularly when activated, produce sulphidopeptide leukotrienes after contact with large particles coated with IgG.     

Immunological activity of covalently linked T-cell epitopes.

Immune responses to proteins necessarily involve the recognition by T lymphocytes of a peptide or peptides derived from a protein complexed with a major histocompatibility antigen. The T-cell response of BALB/c mice to the bacteriophage lambda cI repressor protein (residues 1-102) is directed predominantly towards the epitope contained within a single peptide encompassing residues 12-26. Similar phenomena of immunodominance of a particular peptide have also been observed in other protein systems. The mechanisms that have been suggested to account for the focusing of the T-cell response are partial deletion in the T-cell repertoire, biased antigen processing, and competition for binding to the presenting molecule, the major histocompatibility complex encoded class II transplantation antigen. In a model system with a polypeptide containing two synthetically linked immunologically active epitopes, we now demonstrate the existence of a hierarchy between these epitopes, so that the immune response elicited is directed mainly towards the more immunogenic epitope, whereas the less immunogenic epitope elicits little or no T-cell reactivity. In addition, the same hierarchy of dominance is also apparent when the polypeptide is used to induce tolerance in the periphery in adult mice. The chimaeric peptide can induce tolerance only towards the more immunogenic epitope. These experiments indicate that the rules governing antigen processing and presentation that result in T-cell activation are apparently the same as the rules that govern the processes resulting in the induction of tolerance.