[Biologics and systemic lupus erythematosous : new insights and perspectives]. / Biologiques et lupus érythémateux systémique : nouveautés et perspectives.

Systemic lupus erythematosus is a complex autoimmune disease that remains challenging to treat. Recent advances in the understanding of the pathogenesis of SLE pave the way for the evaluation of biologic medicine. The most promising therapeutic targets in SLE are those that interfere with B cells count or normal function, interferon inhibitors, JAK inhibitors and biologicals that alter the cytokines imbalance that characterizes SLE. Recent phase 3 clinical trials have evaluated the role of belimumab in lupus nephritis and the usefulness of anifrolumab in the treatment of moderate to severe SLE. Many more trials are currently underway and may improve the level of care of patients with SLE in the near future.

Le lupus érythémateux systémique (LES) est une maladie autoimmune complexe, dont le traitement reste un challenge. Les progrès récents sur les connaissances de l'immunopathologie du LES ont permis d'évaluer la place de nouveaux traitements biologiques dans des études cliniques. Celles-ci concernent les anticorps monoclonaux antilymphocytes B, les inhibiteurs de l'interféron et des Janus kinases, ou encore les traitements par administration de cytokines, comme l'interleukine 2. Des études de phase 3 récentes ont évalué la place du bélimumab dans le traitement de la néphrite lupique et l'utilité du blocage de l'interféron par l'anifrolumab dans le traitement du LES modéré à sévère. Plusieurs études cliniques en cours pourraient révolutionner la prise en charge des patients atteints d'un LES dans les années à venir.

[Chronic rhinosinusitis with nasal polyps†: is there a place for monoclonal antibodies in 2020†?] / Allergologie-immunologie - Rhinosinusite chronique avec polypes nasaux†: quelle est la place des anticorps monoclonaux en 2020†?

Chronic rhinosinusitis with nasal polyps is a severe form of chronic rhinosinusitis, which has a strong negative impact on quality of life. Rhinoscopy is helpful for diagnosis, and initial management depends on intra-nasal corticosteroids and sometimes short-term oral corticosteroids (1 to 3 weeks). If well-conducted drug therapy fails, surgery is considered. In the event of post-surgery recurrence or in case of concomitant severe asthma, biologic therapies represent an interesting option. These drugs include dupilumab, mepolizumab, benralizumab and omalizumab. The choice of medication depends on the individual patient context, which includes the presence of atopic dermatitis, eosinophilia, or asthma.

La rhinosinusite chronique avec polypes nasaux constitue une forme sévère de rhinosinusite chronique qui a un impact significatif sur la qualité de vie des personnes affectées. La rhinoscopie aide à poser le diagnostic et la prise en charge initiale repose sur les corticostéroïdes intranasaux avec parfois de courtes cures de corticostéroïdes per os (1 à 3 semaines). En cas d'échec du traitement médicamenteux bien conduit, la chirurgie est envisagée. Lors de récurrence après chirurgie ou en présence d'un asthme difficile à contrôler, les médicaments biologiques constituent une alternative intéressante. Ceux-ci comprennent notamment le dupilumab, le mépolizumab, le benralizumab et l'omalizumab. Le choix de la molécule sera dicté par le contexte individuel du patient, en fonction de la présence d'une dermatite atopique, d'une éosinophilie ou d'un asthme associé.

Innate Lymphoid Cells in Autoimmune Diseases.

Innate lymphoid cells (ILC) are a heterogeneous group of immune cells characterized by lymphoid morphology and cytokine profile similar to T cells but which do not express clonally distributed diverse antigen receptors. These particular cells express transcription factors and cytokines reflecting their similarities to T helper (Th)1, Th2, and Th17 cells and are therefore referred to as ILC1, ILC2, and ILC3. Other members of the ILC subsets include lymphoid tissue inducer (LTi) and regulatory ILC (ILCreg). Natural killer (NK) cells share a common progenitor with ILC and also exhibit a lymphoid phenotype without antigen specificity. ILC are found in low numbers in peripheral blood but are much more abundant at barrier sites such as the skin, liver, airways, lymph nodes, and the gastrointestinal tract. They play an important role in innate immunity due to their capacity to respond rapidly to pathogens through the production of cytokines. Recent evidence has shown that ILC also play a key role in autoimmunity, as alterations in their number or function have been identified in systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Here, we review recent advances in the understanding of the role of ILC in the pathogenesis of autoimmune diseases, with particular emphasis on their role as a potential diagnostic biomarker and as therapeutic targets.

[Allergy to furry animals: myth and reality]. / Allergies aux animaux à poils†: mythes et réalités.

Allergy to furry animals is a frequent health issue, and should be suspected when investigating any yearlong rhinoconjonctivitis or asthma. A detailed medical history and skin prick tests are usually sufficient for diagnosis, and if necessary, specific IgE testing may be performed. In case of proven hypersensitivity, avoidance of animal allergens is the main therapeutic measure, primarily by removing the animal from the patient's environment, in association with symptomatic treatment. If animal removing is impossible, other measures exist to decrease allergen load, but not with the same -efficacy as removing the animal, particularly for asthma. Immunotherapy is available for cat and dog allergy, but indication is to be carefully discussed.

Les allergies aux mammifères à poils sont une problématique ­répandue, et une hypersensibilité aux phanères d'animaux est à rechercher devant toute rhino-conjonctivite ou tout asthme ­perannuels. Une anamnèse soigneuse associée aux prick-tests permet d'orienter le diagnostic, qui sera en cas de doute complété par des dosages d'immunoglobulines E (IgE) spécifiques. Face à une hypersensibilité avérée, l'éviction est la pierre angulaire de la prise en charge, associée à un traitement symptomatique. En cas d'impossibilité pour le patient de se séparer de son animal, des mesures existent pour diminuer la charge en allergènes, bien qu'elles soient insuffisantes pour prévenir toute ­exacerbation des symptômes, surtout en cas d'asthme. Des ­désensibilisations existent pour l'allergie au chat et au chien, à discuter au cas par cas.

IL-27-Induced Type 1 Regulatory T-Cells Produce Oxysterols that Constrain IL-10 Production.

The behaviors of lymphocytes, including CD4+ T helper cells, are controlled on many levels by internal metabolic properties. Lipid metabolites have recently been ascribed a novel function as immune response modulators and perturbation of steroids pathways modulates inflammation and potentially promotes a variety of diseases. However, the impact of lipid metabolism on autoimmune disease development and lymphocyte biology is still largely unraveled. In this line, oxysterols, oxidized forms of cholesterol, have pleiotropic roles on the immune response aside from their involvements in lipid metabolism. The oxysterols 25-hydroxycholesterol (25-OHC) and 7α,25-dihydroxycholesterol (7α,25-OHC) regulate antiviral immunity and immune cell chemotaxis. However, their physiological effects on adaptive immune response in particular on various subset CD4+ T lymphocytes are largely unknown. Here, we assessed oxysterol levels in subset of CD4+ T cells and demonstrated that 25-OHC and transcript levels of its synthesizing enzyme, cholesterol 25-hydroxylase, were specifically increased in IL-27-induced type 1 regulatory T (TR1) cells. We further showed that 25-OHC acts as a negative regulator of TR1 cells in particular of IL-10 secretion via liver X receptor signaling. Not only do these findings unravel molecular mechanisms accounting for IL-27 signaling but also they highlight oxysterols as pro-inflammatory mediators that dampens regulatory T cell responses and thus unleash a pro-inflammatory response.

EBI2 Expression and Function: Robust in Memory Lymphocytes and Increased by Natalizumab in Multiple Sclerosis.

The interaction between oxysterols and the G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2) fine-tunes immune cell migration, a mechanism efficiently targeted by several disease-modifying treatments developed to treat multiple sclerosis (MS), such as natalizumab. We previously showed that memory CD4+ T lymphocytes migrate specifically in response to 7α,25-dihydroxycholesterol (7α,25-OHC) via EBI2 in the MS murine model experimental autoimmune encephalomyelitis. However, the EBI2 expression profile in human lymphocytes in both healthy and MS donors is unknown. Here, we characterize EBI2 biology in human lymphocytes. We observed that EBI2 is functionally expressed on memory CD4+ T cells and is enhanced under natalizumab treatment. These data suggest a significant role for EBI2 in human CD4+ T cell migration, notably in patients with MS. Better knowledge of EBI2 involvement in autoimmunity may therefore lead to an improved understanding of the physiopathology of MS.

Response of mucocutaneous lesions to rituximab in a case of melanoma differentiation antigen 5-related dermatomyositis.

We report the first case in Western Europe of a person presenting with dermatomyositis associated with melanoma differentiation antigen 5 antibodies. She sequentially developed severe mucocutaneous erythematous and itchy lesions of the face, scalp, neck, knees and recurrent aphthae. In addition she presented painful, periungual, edematous digital lesions and small ulcers with digital necrosis. Her rapidly evolving, near-fatal interstitial lung disease responded to high-dose intravenous cyclophosphamide. However, her recurrent mucocutaneous manifestations improved only after rituximab administration.