Rheumatoid arthritis seropositive for the rheumatoid factor is linked to the protein tyrosine phosphatase nonreceptor 22-620W allele

The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes for lymphoid tyrosine phosphatase LYP, involved in the negative regulation of early T-cell activation. An association has recently been reported between the PTPN22-620W functional allele and rheumatoid factor-positive (RF(+)) rheumatoid arthritis (RA), among other autoimmune diseases. Expected linkage proof for consistency cannot be definitely produced by an affected sib-pair (ASP) analysis. Our aim was therefore to search for linkage evidence with the transmission disequilibrium test. DNA from the French Caucasian population was available for two samples of 100 families with one RA patient and both parents, and for 88 RA index cases from RA ASP families. Genotyping was carried out by PCR-restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, genotype relative risk and ASP-based analysis. The transmission disequilibrium test of the PTPN22-620W allele revealed linkage and association for RF(+ )RA (61% of transmission, P = 0.037). The genotype relative risk showed the risk allele in 34% of RF(+ )RA patients and in 24% of controls derived from nontransmitted parental chromosomes (P = 0.047, odds ratio = 1.69, 95% confidence interval = 1.03–2.78). The ASP investigation showed no enriched risk allele in RA multiplex families, resulting in a lack of power of ASP analysis, explaining the published negative results. This study is the first to show linkage of PTPN22 to RF(+ )RA, consistent with PTPN22 as a new RA gene

Food protein-induced enterocolitis syndrome – a review of the literature with focus on clinical management

Food protein-induced enterocolitis syndrome (FPIES) is a potentially severe presentation of non-IgE-mediated gastrointestinal food allergy (non-IgE-GI-FA) with heterogeneous clinical manifestations. Acute FPIES is typically characterized by profuse vomiting and lethargy, occurring classically 1-4 hours after ingestion of the offending food. When continuously exposed to the incriminated food, a chronic form has been described with persistent vomiting, diarrhea, and/or failure to thrive. Although affecting mainly infants, FPIES has also been described in adults. Although FPIES is actually one of the most actively studied non-IgE-GI-FAs, epidemiologic data are lacking, and estimation of the prevalence is based on a limited number of prospective studies. The exact pathomechanisms of FPIES remain not well defined, but recent data suggest involvement of neutrophils and mast cells, in addition to T cells. There is a wide range of food allergens that can cause FPIES with some geographical variations. The most frequently incriminated foods are cow milk, soy, and grains in Europe and USA. Furthermore, FPIES can be induced by foods usually considered as hypoallergenic, such as chicken, potatoes or rice. The diagnosis relies currently on typical clinical manifestations, resolving after the elimination of the offending food from the infant's/child's diet and/or an oral food challenge (OFC). The prognosis is usually favorable, with the vast majority of the case resolving before 5 years of age. Usually, assessment of tolerance acquisition by OFC is proposed every 12-18 months. Of note, a switch to an IgE-mediated FA is possible and has been suggested to be associated with a more severe phenotype. Avoiding the offending food requires education of the family of the affected child. A multidisciplinary approach including ideally allergists, gastroenterologists, dieticians, specialized nurses, and caregivers is often useful to optimize the management of these patients, that might be difficult

Validation of the reshaped shared epitope HLA-DRB1 classification in rheumatoid arthritis

Recently, we proposed a classification of HLA-DRB1 alleles that reshapes the shared epitope hypothesis in rheumatoid arthritis (RA); according to this model, RA is associated with the RAA shared epitope sequence (72–74 positions) and the association is modulated by the amino acids at positions 70 and 71, resulting in six genotypes with different RA risks. This was the first model to take into account the association between the HLA-DRB1 gene and RA, and linkage data for that gene. In the present study we tested this classification for validity in an independent sample. A new sample of the same size and population (100 RA French Caucasian families) was genotyped for the HLA-DRB1 gene. The alleles were grouped as proposed in the new classification: S(1 )alleles for the sequences A-RAA or E-RAA; S(2 )for Q or D-K-RAA; S(3D )for D-R-RAA; S(3P )for Q or R-R-RAA; and X alleles for no RAA sequence. Transmission of the alleles was investigated. Genotype odds ratio (OR) calculations were performed through conditional logistic regression, and we tested the homogeneity of these ORs with those of the 100 first trio families (one case and both parents) previously reported. As previously observed, the S(2 )and S(3P )alleles were significantly over-transmitted and the S(1), S(3D )and X alleles were under-transmitted. The latter were grouped as L alleles, resulting in the same three-allele classification. The risk hierarchy of the six derived genotypes was the same: (by decreasing OR and with L/L being the reference genotype) S(2)/S(3P), S(2)/S(2), S(3P)/S(3P), S(2)/L and S(3P)/L. The homogeneity test between the ORs of the initial and the replication samples revealed no significant differences. The new classification was therefore considered validated, and both samples were pooled to provide improved estimates of RA risk genotypes from the highest (S(2)/S(3P )[OR 22.2, 95% confidence interval 9.9–49.7]) to the lowest (S(3P)/L [OR 4.4, 95% confidence interval 2.3–8.4])

Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment.

There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD). Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively. A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%). In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Amplification optique dans des verres borophosphate de niobium et tellurite dopés aux ions de terres rares présentant un indice optique non linéaire élevé.

Ce travail s'insère, non seulement, dans la compréhension de la relation entre la résonance des terres rares et l'indice non linéaire, mais aussi, dans la recherche de nouveaux matériaux dopés terres rares pour la commutation optique. L'introduction d'oxyde d'erbium dans des verres tellurites et borophosphates de niobium, présentant intrinsèquement une non linéarité optique de 3ème ordre élevée, a été étudiée. Il a été montré qu'il est possible de contrôler le gain et la non linéarité de matériaux dopés grâce à la corrélation établie entre l'analyse structurale et l'étude des propriétés spectroscopiques, de gain et de non linéarité qui dépendent des probabilités de transition 4f ?4f. L'ensemble des résultats permet de mieux comprendre et prédire la variation de l'indice non linéaire d'un matériau amplificateur.This study fits, non only, into the understanding of the relation between the rare earth and the non linear index, but also, into the search of new rare earth doped materials for optical commutation. The erbium oxide introduction in tellurite and borophosphate glasses, showing intrinsically high third order nonlinearity, has been studied. It has been demonstrated that it is possible to correlate the gain and the nonlinearity in doped materials with the structural analysis and the spectroscopic properties. The influence of the 4f ? 4f transition probability on the nonlinearity has been discussed. All the results allow to understand and to predict the nonlinear index variation of an amplifier material

Adolescents and Facebook: Narcissus without (an) echo

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Amplification optique dans des verres borophosphate de niobium et tellurite dopés aux ions de terres rares présentant un indice optique non linéaire élevé

Ce travail s'insère, non seulement, dans la compréhension de la relation entre la résonance des terres rares et l'indice non linéaire, mais aussi, dans la recherche de nouveaux matériaux dopés terres rares pour la communication optique. L'introduction d'oxyde d'erbium dans des verres tellurites et borophosphates de niobium, présentant intrinsèquement une non linéarité optique de 3ème ordre élevée, a été étudiée. Il a été montré qu'il est possible de contrôler le gain et la non linéarité de matériaux dopés grâce à la corrélation établie entre l'analyse structurale et l'étude des propriétés spectroscopiques, de gain et de non linéarité qui dépendent des probabilités de transition 4f-4f. L'ensemble des résultats permet de mieux comprendre et prédire la variation de l'indice non linéaire d'un matériau amplificateur.BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

Le rempart et les structures de la levée 1 - Vix "Le Mont-Lassois" (Côte-d'Or)

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