CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites.

Systemic immunosuppression depletes peripheral blood regulatory B cells in patients with immune thrombocytopenia.

Regulatory B (Breg) cells are potentially implicated in the pathogenesis of immune thrombocytopenia (ITP). We analysed a prospective cohort of newly diagnosed steroid naïve ITP patients enrolled in the multicentre FLIGHT trial and found that the numbers of Bregs in their peripheral blood were similar to healthy controls. In contrast, Breg numbers were significantly reduced in ITP patients treated with systemic immunosuppression (glucocorticoids or mycophenolate mofetil).

Factors Predicting Long-term Outcome and the Need for Surgery in Graves Orbitopathy: Extended Follow-up From the CIRTED Trial.

Unlabelled: Graves orbitopathy is both disabling and disfiguring. Medical therapies to reduce inflammation are widely used, but there is limited trial data beyond 18 months of follow-up.

Methods: Three-year follow-up of a subset of the CIRTED trial (N = 68), which randomized patients to receive high-dose oral steroid with azathioprine/placebo and radiotherapy/sham radiotherapy.

The Effect of Ophthalmic Surgery for Graves' Orbitopathy on Quality of Life: A Systematic Review and Meta-Analysis.

Graves' orbitopathy (GO) has a profound negative impact on quality of life. Surgery is undertaken to preserve vision, correct diplopia, and improve aesthetics. We sought to quantify the effect of different surgical approaches on quality of life.

Identification of an intraocular microbiota.

The current dogma in ophthalmology and vision research presumes the intraocular environment to be sterile. However, recent evidence of intestinal bacterial translocation into the bloodstream and many other internal organs including the eyes, found in healthy and diseased animal models, suggests that the intraocular cavity may also be inhabited by a microbial community. Here, we tested intraocular samples from over 1000 human eyes.

Ibrutinib-related uveitis: A report of two severe cases.

Introduction: Ibrutinib is a small-molecule drug approved for the treatment of haematological disorders and is known to be associated with visual disturbances, but uveitis has not yet been reported as an adverse effect of this medication. We present two cases of ibrutinib-associated severe uveitis in patients with chronic lymphocytic leukaemia.

Case Description: Our first case is a 65-year-old woman who presented with acute onset of bilateral fibrinous anterior uveitis 1 day after starting ibrutinib.

Glucocorticoid treatment in patients with newly diagnosed immune thrombocytopenia switches CD14 CD16 intermediate monocytes from a pro-inflammatory to an anti-inflammatory phenotype.

Immune thrombocytopenia (ITP) is thought to result from an aberrant adaptive autoimmune response, involving autoantibodies, B and T lymphocytes, directed at platelets and megakaryocytes. Previous reports have demonstrated skewed CD4 T-helper subset distribution and enhanced production of pro-inflammatory cytokines such as interleukin 17A and interferon gamma. The role of monocytes (MCs) in ITP is less widely described, but innate immune cells have a role in shaping CD4 T-cell phenotypes.

IL-10 and IL-17 expression by CD4 T cells is altered in corticosteroid refractory immune thrombocytopenia (ITP).

Background: Corticosteroids remain the first-line treatment for patients with immune thrombocytopenia (ITP). However, 20% to 30% of patients do not respond to treatment at tolerable doses. This variation in corticosteroid efficacy is replicated in other autoimmune diseases and may have an adaptive immune basis.

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial.

Background: Uveitis associated with juvenile idiopathic arthritis is a cause of major ocular morbidity. A substantial proportion of children are refractory to systemic methotrexate and TNF inhibitors. Our aim was to study the safety and efficacy of tocilizumab in children with juvenile idiopathic arthritis-associated uveitis refractory to both methotrexate and TNF inhibitors.

Intravenous indocyanine green dye is insufficient for robust immune cell labelling in the human retina.

It is not currently possible to reliably visualise and track immune cells in the human central nervous system or eye. Previous work demonstrated that indocyanine green (ICG) dye could label immune cells and be imaged after a delay during disease in the mouse retina. We report a pilot study investigating if ICG can similarly label immune cells within the human retina.

New insights into the pathogenesis and nonsurgical management of Graves orbitopathy.

Graves orbitopathy, also known as thyroid eye disease or thyroid-associated orbitopathy, is visually disabling, cosmetically disfiguring and has a substantial negative impact on a patient's quality of life. There is increasing awareness of the need for early diagnosis and rapid specialist input from endocrinologists and ophthalmologists. Glucocorticoids are the mainstay of treatment; however, recurrence occurs frequently once these are withdrawn.

Intermediate Monocytes in Acute Alcoholic Hepatitis Are Functionally Activated and Induce IL-17 Expression in CD4 T Cells.

In humans, the three main circulating monocyte subsets are defined by their relative cell surface expression of CD14 and CD16. They are all challenging to study because their characteristics are strongly context specific, and this has led to a range of conflicting reports about their function, which is especially so for CD14CD16 (intermediate) monocytes. Ex vivo cultures are also often confounded by the concomitant use of immunosuppressive drugs.

The DNA Methylation Inhibitor Zebularine Controls CD4 T Cell Mediated Intraocular Inflammation.

CD4 T cell mediated uveitis is conventionally treated with systemic immunosuppressive agents, including corticosteroids and biologics targeting key inflammatory cytokines. However, their long-term utility is limited due to various side effects. Here, we investigated whether DNA methylation inhibitor zebularine can target CD4 T cells and control intraocular inflammation.

Human Th17 cells produce a soluble mediator that increases podocyte motility via signaling pathways that mimic PAR-1 activation.

The specific pathogenesis of idiopathic nephrotic syndrome (NS) is poorly understood, and the role of immune mediators remains contentious. However, there is good evidence for the role of a circulating factor, and we recently postulated circulating proteases as candidate factors. Immunosuppressive therapy with glucocorticoids (GCs) and T cell inhibitors are widely used in the clinical treatment of NS.

Glucocorticoid Receptor-α and MKP-1 as Candidate Biomarkers for Treatment Response and Disease Activity in Vogt-Koyanagi-Harada Disease.

Purpose: To investigate the potential of utilizing the expression of genes for glucocorticoid receptor (GR) and mitogen-activated protein kinase phosphatase-1 (MKP-1) as biomarkers of corticosteroid (CS) refractoriness and disease activity in patients with Vogt-Koyanagi-Harada (VKH) disease.

Design: Prospective cohort study.

Methods: Twenty VKH patients receiving their first cycle of CS treatment in the absence of additional systemic immunosuppressive therapy and a control group of fifteen healthy volunteers were recruited from the University of Chile (Santiago, Chile) and US National Institutes of Health (Bethesda, United States).

T Cell Cytokine Expression Predicts Survival in Patients with Severe Alcoholic Hepatitis.

Alcoholic hepatitis (AH) is an acute inflammatory liver condition with high early mortality rate. Steroids improve short-term survival but nonresponders have the worst outcomes. There is a clinical need to identify these high-risk individuals at the time of presentation.

The Bromodomain and Extra-Terminal Protein Inhibitor OTX015 Suppresses T Helper Cell Proliferation and Differentiation.

Background: Dynamic epigenetic alterations accompanying CD4+ T helper cell differentiation have been implicated in multiple autoimmune diseases. The bromodomain and extra-terminal (BET) proteins are epigenetic regulators that recognize and bind to acetylated histones in chromatin and are targets for pharmacological inhibition. In this study we tested a new BET inhibitor under clinical development, OTX015, to interrogate its effects on key CD4+ T cell subsets associated with autoimmunity.

CytoBinning: Immunological insights from multi-dimensional data.

New cytometric techniques continue to push the boundaries of multi-parameter quantitative data acquisition at the single-cell level particularly in immunology and medicine. Sophisticated analysis methods for such ever higher dimensional datasets are rapidly emerging, with advanced data representations and dimensional reduction approaches. However, these are not yet standardized and clinical scientists and cell biologists are not yet experienced in their interpretation.

Establishing the usefulness of the GO-QOL in a UK hospital-treated population with thyroid eye disease in the CIRTED trial.

Thyroid eye disease (TED) is a potentially sight-threatening and cosmetically disfiguring condition arising in 25-50% of patients with Graves' hyperthyroidism. CIRTED is the first study to evaluate the long-term role of radiotherapy and prolonged immunosuppression with azathioprine in treating TED, one aim of which was to validate the use of the English version of GO-QOL in an UK population with TED. In a three stage design over a 48 week period, the GO-QOL was tested and compared to a general measure of quality of life (WHOQOL-Bref).

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.

Purpose: Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area.

Design: Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.