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Le système immunitaire de l'œil présente des caractéristiques particulières et spécifiques. En effet, cet organe bénéficie d'un statut particulier dit de privilège immun qui permet, via différents mécanismes, de limiter la réponse inflammatoire immunitaire afin de protéger la vision. Les atteintes pathologiques oculaires sont de ce fait souvent localisées. De plus, les manifestations cliniques de ces pathologies sont parfois peu spécifiques, ce qui rend leur diagnostic difficile. L'exploration biologique du système immunitaire de l'œil est donc une aide précieuse dans le diagnostic et le suivi de certaines de ces pathologies. Sera notamment présenté ici l'intérêt du dosage dans les prélèvements oculaires de l'interleukine (IL)-10 et celui du ratio IL-10/IL-6 pour le diagnostic et le suivi du lymphome oculaire, des cytokines pro-inflammatoires pour les uvéites et des IgE totales pour les conjonctivites allergiques. The immune system of the eye has special and specific characteristics. Indeed, this organ benefits from a special status called immune privilege which allows, via different mechanisms, to limit the immune inflammatory response in order to protect vision. Ocular pathologies are therefore often localized. In addition, the clinical manifestations of these pathologies could be non-specific, which makes their diagnosis difficult. The biological exploration of the immune system of the eye is therefore a valuable help in the diagnosis and monitoring of some of these pathologies: this article presents in particular the interest of interleukin (IL)-l0 assay and the IL-I0/IL-6 ratio in ocular samples for the diagnosis and monitoring of intraocular lymphoma, of pro-inflammatory cytokines for uveitis and of total IgE for allergic conjunctivitis. [ABSTRACT FROM AUTHOR]

L'utilisation croissante des traitements par cellules CAR-T ces dernières années a révolutionné la prise en charge des patients atteints d'hémopathies. Les biologistes et, plus parti- culièrement, les immunologistes ont dû s'adapter pour développer, en parallèle, des tests biologiques permettant de prédire et suivre l'efficacité du traitement et la survenue d'effets indésirables comme le syndrome de relargage cytokinique. Les pistes les plus étudiées actuellement concernent le dosage des cytokines circulantes et le suivi des cellules CAR-T par cytométrie en flux ou biologie moléculaire. The increasing use of CAR-T cells therapies in recent years has transformed the management of patients with hematologic malignancies. The biologists and especially the immunologists had to adapt and develop biological tests for the prediction and monitoring of treatment efficacy and adverse events onset like cytokine release syndrome. To date, most studies focus on blood cytokine dosage and CAR-T cells monitoring using flow cytometry or molecular biology. [ABSTRACT FROM AUTHOR]

Le dosage des immunoglobulines de type E (IgE), dites spécifiques des réactions d'hypersensibilité IgE dépendantes, fait maintenant partie intégrante du diagnostic étiologique de l'allergie. Dans les années 1990, le clonage et la caractérisation des allergènes moléculaires et l'évolution parallèle des technologies de type « microarray » ont conduit au développement des premières biopuces multi-allergéniques. Ces tests ont ainsi permis d'établir des profils de sensibilisation pour chaque patient en recherchant simultanément des IgE spécifiques dirigées contre plus de 100 allergènes différents, ce qui a été une avancée majeure sur le plan épidémiologique et diagnostique. Néanmoins, ces technologies présentent quelques limites, concernant notamment la sensibilité et la quantification (tests semi-quantitatifs). En raison de leur coût, de leurs avantages et inconvénients, les biopuces multi-allergéniques doivent être réservées à des indications cliniques particulières, notamment chez les patients polysensibilisés présentant des allergies multiples ainsi que pour l'exploration d'anaphylaxies idiopathiques. The immunoglobulin E-type (IgE) assay, so-called specific for IgE-dependent hypersensitivity reactions, is now an integral part of the etiological diagnosis of allergy. In the 1990s, the cloning and characterization of molecular allergens and the parallel evolution of microarray technologies led to the development of the first multi-allergenic biochips. These tests have made it possible to establish sensitization profiles for each patient by simultaneously searching for specific IgE directed against more than 100 different allergens which has been a major breakthrough in epidemiological and diagnostic terms. Nevertheless, these technologies have some limitations, especially concerning sensitivity and quantification (semi-quantitative assays). Due to their cost, advantages and disadvantages, multi-allergenic biochips must be reserved for particular clinical indications, especially in polysensitized patients with multiple allergies and for the exploration of idiopathic anaphylaxis. [ABSTRACT FROM AUTHOR]

La vérification d'une méthode de dosage selon la norme NF/EN/ISO 15189 requiert l'analyse des performances de la technique (répétabilité, fidélité intermédiaire, exactitude et incertitude de mesure) avant toute utilisation en routine. Les coefficients de variation (CV) des résultats de précision intra-essai et inter-essais obtenus doivent être comparés à ceux des pairs et à ceux qui pratiquent ces mêmes dosages quelle que soit la technique. En l'absence de publications nationales ou internationales pour les IgE spécifiques et la tryptase, le réseau des biologistes des centres hospitaliers AllergoBioNet a analysé les résultats fournis par 24 centres pour proposer des limites acceptables des critères de performance pour le dosage des IgE totales et spécifiques et de la tryptase. Checking a dosing method according to NF/EN/ISO 15189 standard requires analysis of the performance of the technique (repeatability, intermediate fidelity, accuracy and measurement uncertainty) before routine use and follow-up annually. The coefficients of variation (CV) of the intra-assay and inter-assays accuracy results obtained must be compared with those of peers and those who perform the same determination regardless of the technique. In the absence of national or international guidelines for monitoring the performance of specific IgE and tryptase assay, the French network of hospital laboratories AllergoBioNet analysed the results provided by 24 centers and propose recommendations for total IgE, specific IgE and tryptase assays. [ABSTRACT FROM AUTHOR]

Aim of the study Evaluate the added value of screening anti-ZnT8 antibodies (ZnT8A) in addition to the classical anti-GAD (GADA) and anti-IA-2 (IA-2A) antibodies for the diagnosis of type-1 diabetes (T1D) within a large cohort of both children and adults. Materials and methods Retrospective 2-year study including 516 patients (215 children, 301 adults) who had blood tests at diabetes onset and/or for diabetes classification. ZnT8A, GADA, and IA-2A were analyzed in all samples. Results Among those individuals included, 142 (28%) were ZnT8A-positive. A total of 228/516 suffered from T1D, of whom 110 (48%) were ZnT8A-positive and 166 (73%) GADA and/or IA-2A positive. When adding ZnT8A to GADA/IA-2A, 184 (81%) patients were positive for ≥ 1 Ab. Regarding the 122 patients at T1D onset, 75 (61%) were positive for ZnT8A and the proportion of patients with T1D with ≥ 1 Ab reached 89%. The highest prevalence of ZnT8A was observed in children aged 6–10 years. Fourteen of the 124 patients positive for ZnT8A with a known clinical diagnosis suffered from a disease other than T1D. Conclusions ZnT8A should be included in routine evaluation at diabetes onset and is a valuable biological marker to classify newly-diagnosed diabetics. The predictive value in our high-risk subjects has to be confirmed. [ABSTRACT FROM AUTHOR]

• The IFN score can drive the use of tofacitinib in dermatomyositis (DM). • Tofacitinib should be considered for DM patients with refractory calcinosis. • Prolonged treatment with tofacitinib is required to allow regression of calcinosis. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aims of our study were to compare in a cohort of 705 patients the diagnostic performance of two tests to detect autoantibodies to cyclic citrullinated peptides (CCP) and to determine whether a bead-based assay within a multiplex flow immunoassay (MFA) can be used instead of an enzyme linked immunosorbent assay (ELISA) technique in routine practice. Design and methods: Six hundred and thirty patients with rheumatic symptoms and 75 patients with systemic lupus erythematosus (SLE) were tested for anti-CCP autoantibodies using two techniques: ELISA (Inova) and MFA (BioPlex®, Bio-Rad). Results: Using kappa coefficient, there was an excellent agreement between ELISA and MFA when comparing 630 patients with rheumatic symptoms (κ coefficient, 0.82). In this cohort 174 patients were identified as suffering from RA, while 456 patients suffered from other diseases. Sensitivity and specificity values of anti-CCP autoantibodies for RA were 70.7% and 92.3% for ELISA and 64.4% and 92.8% for MFA. The positive and negative predictive values were 77.4% and 89.2% for ELISA and 77.2% and 87.2% for MFA, respectively. There were no differences in the diagnostic performances between the two assays (Z=0.67). The specificity values of anti-CCP autoantibodies analysing patients with SLE were 97.3% with MFA and 96% with ELISA with an excellent agreement between the methods (98.7%; κ coefficient, 0.79). Conclusion: Concordance between ELISA and MFA is high in routine practice. Overall, MFA is a powerful tool for rapid assessment of anti-CCP autoantibodies and can replace the ELISA technique, which could be used as a second-line test in some cases. [Copyright &y& Elsevier]

Milk polar lipids (MPL) are specifically rich in milk sphingomyelin (MSM) which represents 24% of MPL. Beneficial effects of MPL or MSM have been reported on lipid metabolism, but information on gut physiology is scarce. Here we assessed whether MPL and MSM can impact tight junction expression. Human epithelial intestinal Caco-2/TC7 cells were incubated with mixed lipid micelles devoid of MSM (Control) or with 0.2 or 0.4 mM of MSM via pure MSM or via total MPL. C57Bl/6 mice received 5 or 10 mg of MSM via MSM or via MPL (oral gavage); small intestinal segments were collected after 4 h. Impacts on tight junction and cytokine expressions were assessed by qPCR; IL-8 and IL-8 murine homologs (Cxcl1, Cxcl2) were analyzed. In vitro, MSM increased tight junction expression (Occludin, ZO-1) vs Control, unlike MPL. However, no differences were observed in permeability assays (FITC-dextran, Lucifer yellow). MSM increased the secretion and gene expression of IL-8 but not of other inflammatory cytokines. Moreover, cell incubation with IL-8 induced an overexpression of tight junction proteins. In mice, mRNA level of Cxcl1 and Cxcl2 in the ileum were increased after gavage with MSM vs NaCl but not with MPL. Altogether, these results suggest a specific action of MSM on intestinal tight junction expression, possibly mediated by IL-8. Our study provides clues to shed light on the beneficial effects of MPL on intestinal functions and supports the need for further mechanistic exploration of the direct vs indirect effects of MSM and IL-8 on the gut barrier. [ABSTRACT FROM AUTHOR]