Background We report here a case of a healthy 23-year-old female patient who was assessed at the gynecology emergency department for genital ulcers, fever, and blurred vision. After suspicion of ...herpes simplex virus-2 lesions, the diagnosis of Behçet's disease was made. We report this case with the aim of including Behçet's disease in the differential diagnosis of genital ulcers, and emphasize the emergency of the vision loss that can be irreversible. Case presentation A healthy 23-year-old European female patient was assessed by gynecology in the emergency department for genital lesions associated with fever and blurred vision. At first, these lesions were suspected to be primary herpes simplex virus-2 infection One day later, she experienced decreased visual acuity in both eyes. After 4 days of worsening genital ulcers and persistent blurred vision, the patient was referred to the ophthalmology department. Fundoscopic examination showed retinal hemorrhages that were consistent with the first presentation of Behçet's disease. Conclusions This case demonstrates that genital ulcers can be the very initial symptom of this ophthalmologic emergency. The differential diagnosis of genital ulcers is challenging. Behçet's disease should be included, especially when associated with systemic or ocular manifestations, and should be considered an emergency for the gynecologist to prevent long-term vision loss. Keywords: Behçet, Genital ulcers, Ophthalmologic emergency, Macular occlusion, Immunosuppressors
Abstract Perturbation of steroids pathways is linked to inflammation and chronic diseases, however the underlying mechanism remains unclear. Oxysterols, oxidized forms of cholesterol, are not only ...essential for bile synthesis and sterol transportation but have recently been shown to contribute to the immune response. In addition, serum oxysterols levels have been proposed as suitable candidate biomarkers for neurological diseases such as multiple sclerosis (MS). However how oxysterols modulate adaptive immunity is unknown and their functions in autoimmunity have not been investigated. The enzyme cholesterol 25 hydroxylase (Ch25h) is the rate limiting step to synthesize the oxysterol 7α,25-dihydroxycholesterol (7α,25-OHC) from cholesterol. We here report, using the MS murine model experimental autoimmune encephalomyelitis (EAE), that Ch25h deletion significantly attenuated EAE disease course by limiting trafficking of pathogenic CD4+ T lymphocytes to the central nervous system (CNS). Mechanistically, we show a critical involvement for oxysterols in recruiting leukocytes into inflamed tissues and propose that 7α,25-OHC preferentially promotes the migration of activated CD44+ CD4+ T cells by binding the G protein-coupled receptor called Epstein-Barr virus induced gene 2 (EBI2). Collectively, our results support a pro-inflammatory role for oxysterols during EAE and identify oxysterols as a potential therapeutic target to treat autoimmune diseases.
Background
Equine sarcoids (ES) are the most common cutaneous tumors in equids. Systemic treatment options are sparse. Subcutaneous (SC) injections of Viscum album extract (VAE) demonstrate efficacy ...as a systemic treatment directed against ES.
Objectives/Aim
To critically assess the therapeutic efficacy of orally administered VAE.
Animals
Forty‐five ES‐affected, privately owned, 3–12 year‐old horses.
Methods
A 3‐armed randomized placebo‐controlled, double‐blinded study was conducted in a double‐dummy design. Horses were subjected to oral administration and SC injections of either VAE or placebo (VAE oral/placebo SC, VAE SC/placebo oral, placebo oral/placebo SC) over a 7‐month treatment period. Primary endpoint was the change of baseline of a composite index of ES number and ES area after 14 months. Second endpoint was the clinical response.
Results
No statistically significant difference in the composite endpoint between the 3 study arms was found. The primary endpoint showed 4 (27%) horses in the VAE oral group with complete ES regression, 3 (21%) in the VAE SC injection group, and 2 (13%) in the placebo group. The clinical response revealed complete or partial regression in 6 horses of the oral VAE group (40%), 4 of the SC injection group (29%), and 4 of the placebo group (25%). Direct comparison of oral VAE and placebo showed an odds ratio, stratified for prognosis of 2.16 (95%‐CI: 0.45–10.42) and a P‐value of 0.336.
Conclusion and Clinical Importance
Oral administration of VAE is well tolerated. No statistically significant difference in the effectiveness of systemic VAE versus placebo against ES was found.
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.
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 (T
1) cells. We further showed that 25-OHC acts as a negative regulator of T
1 cells in particular of IL-10 secretion
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.
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.
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•EBI2 expression is maximal on human CD4+ T cells and CD19+ B cells•EBI2 is functional in human T and B cells•Natalizumab alters EBI2 expression and function in memory CD4+ T cells
Clottu et al. investigated the expression and function of the oxysterol receptor EBI2 in human primary lymphocytes. They show that EBI2 regulates human lymphocyte migration in vitro and that its expression and migratory response are increased in memory CD4+ T cells from multiple sclerosis patients treated with natalizumab.
This research studies the practices related to the conception of training "on demand" in the field of continuous training of teachers. Training "on demand" adapts itself to the problems of ...professionals. The analysis of the demand faces the complexity of the different contexts as well as the diversity of professionals' questions. This paper emphasizes relevant elements based on a case study to show how the trainer who designs the concept takes into account factors present during the conception i.e. the various aspects of context, contents and learners. The method chosen for the research is qualitative and built related to a specific scholar context in which the teachers have difficulties in their daily work specifically in the field of French language. The training design provides various modalities including conferences, discussion groups, and support in the classes in the presence of the pupils. Different measures to support the teachers in regular classes are provided by specialized professionals. As the schoolchildren come from a great number of cultures, speak diverse languages and attend the courses of regular schools near their homes, this original design takes place in an inclusive context and aims at enabling the teachers to develop reflective practice.
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.
Background: Equine sarcoids (ES) are common, difficult to treat, and have high recurrence rates. Viscum album extracts (VAE) are used in human cancer treatment. Hypothesis: That therapy with VAE ...(Iscador P) is effective in the treatment of ES. Animals: Fifty-three horses (444 ES); 42 were treated with VAE or placebo as monotherapy; 11 were treated with VAE or placebo after selective excision of ES. Methods: Prospective, randomised, blinded, clinical trial. Horses were randomly assigned to treatment (VAE; n = 32) or control group (Placebo; n = 21). One milliliter of VAE (Iscador P) in increasing concentrations from 0.1 to 20 mg/mL or physiological NaCl solution was given SC 3 times a week over 105 days. Number, localization, and type of the ES were documented over 12 months. A subset of 163 clinically diagnosed equine sarcoid (CDES) lesions (95 VAE, 68 Placebo) was evaluated in detail, considering clinical findings and tumor volume. Results: No undesired adverse effects were observed except for mild edema at the injection site in 5 of 32 horses (16%). Complete or partial regression was observed in 13 horses of the VAE group (41%) and in 3 of the control horses (14%; P < .05). After VAE treatment, 48 of 95 CDES (67%) showed an improvement compared with 17 of 68 CDES in the control group (40%; P < .01). Twenty-seven CDES had disappeared completely in the VAE group (38%) compared with 9 CDES in the control group (13% NS). Conclusions and Clinical Importance: VAE (Iscador P) represents a safe and effective treatment for CDES.
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