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Background:Despite substantial improvements in long-term clinical outcomes, a significant proportion of rheumatoid arthritis (RA) patients still fail to respond to treatment adequately, and early prognostic biomarkers of response are missing. Single-cell transcriptomic studies on RA synovial tissue (ST) have shown that MerTK is highly expressed in “anti-inflammatory” macrophages [1]. It has also been suggested that synovial macrophages isolated from RA patients in remission are characterised by a CD206+/MerTK+ signature [2]. Finally, monocyte-derived macrophages from RA patients treated with TNF-inhibitors (TNF-i) up-regulate MerTK.Objectives:To assess i) the modulation of synovial tissue MerTK+ macrophages upon treatment with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and ii) the relationship between baselineMerTKgene expression and response to TNFi.Methods:ST was obtained by US-guided synovial biopsies of an inflamed peripheral joint in patients with early (Results:Before any treatment intervention, the percentage of MerTK+CD206+ macrophages was significantly higher in RA patients with low (DAS285.1) disease activity (24.5±20.1 versus 4.8±4.8, pConclusion:Our whole-tissue protein expression data further support the hypothesis that a selective expansion of the MerTK+ macrophage subset characterise patients achieving remission. Moreover, the pre-treatment up-regulation of the MerTK gene in future responders to TNFi suggest that MerTK is implicated in modulating synovial inflammatory responses and may be exploited as a therapeutic target in RA.References:[1]F. Zhang et al, Nature Immunology, vol. 20, no. 7, pp. 928–942, 2019.[2]S. R. Finlay at al, Annals of the Rheumatic Diseases, vol. 77, Supplement 2, pp. 183–183, 2018.[3]Y. Degboé et al, Frontiers in Immunology, vol. 10, p. 3, 2019.Acknowledgments:Versus ArthritisDisclosure of Interests:None declared

Aim: To characterise the ocular phenotype of a family segregating the splice site mutation c.2189+1G>T in the tyrosine kinase receptor gene MERTK . Methods: Five affected children of a consanguineous Moroccan family were investigated by ophthalmic examinations, including fundus photography, autofluorescence (FAF) imaging, optical coherence tomography (OCT), psychophysical and electrophysiological methods. Results: Affected children were between 5 and 19 years of age, allowing an estimation of disease progression. Electroretinography demonstrated loss of scotopic and photopic function in the first decade of life. Younger siblings showed drusen-like deposits with focal relatively increased FAF in the macular area. With increasing age, a yellowish lesion with relatively increased FAF and subsequent macular atrophy developed. Visual acuity deteriorated with age and ranged between 20/50 in the best eye of the youngest affected and 20/400 in the worst eye of the oldest affected sibling. Spectral-domain OCT revealed debris-like material in the subneurosensory space. Conclusion: The splice site mutation c.2189+1G>T in MERTK causes rod–cone dystrophy with a distinct macular phenotype. The debris in the subneurosensory space resembles that in the Royal College of Surgeons (RCS) rat being the mertk animal model. Patients might therefore benefit from advances in gene therapy that were previously achieved in the RCS rat.

6 páginas, 8 figuras, 2 tablas.-- Licence Creative Commons, attribution, Non-commercial licence.-- et al., [Background/aim]: MERTK, a tyrosine kinase receptor protein expressed by the retinal pigment epithelium (RPE), is mutated in both rodent models and humans affected by retinal disease. This study reports a survey of families for Mertk mutations and describes the phenotype exhibited by one family. [Methods]: 96 probands with retinal dystrophy, consistent with autosomal recessive segregation, were screened by direct sequencing. A family homozygous for a likely null allele was investigated clinically. [Results]: A novel frame shifting deletion was identified in one of 96 probands. Other polymorphisms were detected. The deletion allele occurred on both chromosomes of four affected family members. Electrophysiology demonstrated early loss of scotopic and macular function with later loss of photopic function. Visual acuities and visual fields were preserved into the second decade. Perception of light vision was present in a patient in the fourth decade. A “bull’s eye” appearance and a hyperautofluorescent lesion at the central macula were consistent clinical findings. [Conclusions]: Mutations in Mertk are a rare cause of ARRP in humans. The study extends the phenotypic characteristics of this retinal dystrophy and shows distinctive clinical signs that may improve its clinical identification. The moderate severity and presence of autofluorescence implies that outer segment phagocytosis is not entirely absent., the special trustees of Moorfields Eye Hospital, the Wellcome Trust, and the Foundation Fighting Blindness for their generous sponsorship.