Catalogue of inherited autosomal recessive disorders found amongst the Roma population of Europe.

Background: The Roma population are an endogamous, genetically isolated, minority population who migrated from North-Western India to Europe from the 10 Century throughout the Byzantine period and continues to the present day. Approximately 10-12 million Romani people reside in segregated settlements in Europe, and smaller populations live in North America and China. In addition to the endogamy, they also practice consanguinity.

Pharmacokinetics, Pharmacodynamics, Bioavailability, and Immunogenicity of Obexelimab Following Subcutaneous Administration in Healthy Japanese and Non-Japanese Volunteers.

Introduction: Obexelimab is an investigational, bifunctional, non-depleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells. In clinical trials, intravenous (IV) administration of obexelimab has been well-tolerated, and demonstrated clinical activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and immunoglobulin G4-related disease. This study was performed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of obexelimab following subcutaneous (SC) administration, and compare PK/PD profiles between healthy Japanese and non-Japanese volunteers.

A new class of 7-deazaguanine agents targeting autoimmune diseases: dramatic reduction of synovial fibroblast IL-6 production from human rheumatoid arthritis patients and improved performance against murine experimental autoimmune encephalomyelitis.

A simple assay involving the measurement of IL-6 production in human synovial fibroblasts from rheumatoid arthritis patients has been utilised to select candidates from a targeted library of queuine tRNA ribosyltransferase (QTRT) substrates for subsequent screening in murine experimental autoimmune encephalomyelitis (EAE - a model of multiple sclerosis). The activity assay discriminated between poor and excellent 7-deazaguanine QTRT substrates and allowed the identification of several structures which subsequently outperformed the previous lead in EAE. Two molecules were of significant promise: one rigidified analogue of the lead, and another considerably simpler structure incorporating an oxime motif which differs structurally from the lead to a considerable extent.

Evaluation of the safety, efficacy, and mechanism of action of obexelimab for the treatment of patients with IgG4-related disease: an open-label, single-arm, single centre, phase 2 pilot trial.

Background: Obexelimab is a bifunctional, non-cytolytic, humanised monoclonal antibody that binds CD19 and Fc gamma receptor IIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells. We aimed to evaluate the safety, clinical efficacy, and pharmacodynamic effects of obexelimab in patients with active IgG4-related disease.

Methods: We conducted an open-label, single-arm, single centre, phase 2 pilot trial at the Massachusetts General Hospital in Boston, MA, USA.

Type II NKT Cell Agonist, Sulfatide, Is an Effective Adjuvant for Oral Heat-Killed Cholera Vaccines.

Oral vaccination has the potential to offer a safer and more efficacious approach for protection against enteric pathogens than injection-based approaches, especially in developing countries. One key advantage is the potential to induce intestinal immune responses in addition to systemic immunity. In general, antigen delivery via the oral route triggers weak immune responses or immunological tolerance.

Anti-inflammatory Trained Immunity Mediated by Helminth Products Attenuates the Induction of T Cell-Mediated Autoimmune Disease.

Recent studies have suggested that the innate immune system can display characteristics of immunological memory and this has been called "innate immune memory" or "trained immunity." Certain fungal products have been shown to induce epigenetic imprinting on monocytes/macrophages that results in heightened inflammatory responses to subsequent stimuli. Here we report that innate immune cells can be trained to be more anti-inflammatory following exposure to products of a helminth pathogen.

Helminths products directly modulate T cells that mediate experimental autoimmune encephalomyelitis.

Infection with helminths can protect against the development of autoimmune diseases and this has been associated with induction of anti-inflammatory innate immune responses and Tregs. Here, we demonstrate that helminth-derived products can directly target T cells, especially IL-17-secreting γδ T cells that play a key pathogenic role in CNS autoimmune disease.

Aflibercept in Diabetic Macular Oedema Previously Refractory to Standard Intravitreal Therapy: An Irish Retrospective Study.

Introduction: To determine visual and anatomical outcomes of diabetic macular oedema (DMO) patients in a tertiary centre following conversion to aflibercept having been refractory to previous treatment with bevacizumab/ranibizumab.

Methods: A retrospective case series of patients with a diagnosis of DMO undergoing aflibercept intravitreal therapy for at least 6 months who had previous treatment with three consecutive bevacizumab/ranibizumab injections pre-switch. Exclusion criteria included other procedures affecting visual outcome performed within the treatment period.

Assessment of delays in presentation of patients with retinal detachment to a tertiary referral centre.

The referral pathway of patients with retinal detachment from primary care providers to a tertiary care ophthalmic unit was examined, in order to determine the length and source of any delays between the onset of symptoms and arrival at the hospital. A prospective survey of all symptomatic patients (n = 60) admitted for primary rhegmatogenous retinal detachment surgery was carried out over an 8 week period. Twenty-one patients were referred by their optometrists and 18 by their general practitioners.

Telangiectasis as a cause of intra-schitic haemorrhage in optic disc pit maculopathy.

Purpose: To present a patient with the novel finding of vascular telangiectasis as a cause of intra-schitic haemorrhage, occurring in optic disc pit-associated maculopathy.

Methods: A clinical history was detailed. Clinical examination included visual acuity assessment and slit-lamp microscopy.