Chronic monarthritis of the ankle in a young man Gonzalez‐Martin, Jorge J.; San Jose, Begoña Gutierrez; Sanchez‐Pernaute, Olga
Arthritis care & research,
March 2011, Letnik:
63, Številka:
3
Journal Article, Conference Proceeding
Objective
MicroRNAs (miRNA) have recently emerged as a new class of modulators of gene expression. In this study we investigated the expression, regulation, and function of miR‐155 and miR‐146a in ...rheumatoid arthritis (RA) synovial fibroblasts (RASFs) and RA synovial tissue.
Methods
Locked nucleic acid microarray was used to screen for differentially expressed miRNA in RASFs treated with tumor necrosis factor α (TNFα). TaqMan‐based real‐time polymerase chain reaction was applied to measure the levels of miR‐155 and miR‐146a. Enforced overexpression of miR‐155 was used to investigate the function of miR‐155 in RASFs.
Results
Microarray analysis of miRNA expressed in RASFs treated with TNFα revealed a prominent up‐regulation of miR‐155. Constitutive expression of both miR‐155 and miR‐146a was higher in RASFs than in those from patients with osteoarthritis (OA), and expression of miR‐155 could be further induced by TNFα, interleukin‐1β, lipopolysaccharide, poly(I‐C), and bacterial lipoprotein. The expression of miR‐155 in RA synovial tissue was higher than in OA synovial tissue. Enforced expression of miR‐155 in RASFs was found to repress the levels of matrix metalloproteinase 3 (MMP‐3) and reduce the induction of MMPs 3 and 1 by Toll‐like receptor ligands and cytokines. Moreover, compared with monocytes from RA peripheral blood, RA synovial fluid monocytes displayed higher levels of miR‐155.
Conclusion
This study provides the first description of increased expression of miRNA miR‐155 and miR‐146a in RA. Based on these findings, we postulate that the inflammatory milieu may alter miRNA expression profiles in resident cells of the rheumatoid joints. Considering the repressive effect of miR‐155 on the expression of MMPs 3 and 1 in RASFs, we hypothesize that miR‐155 may be involved in modulation of the destructive properties of RASFs.
To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated.
A longitudinal ...multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry pNEumology RhEumatology Autoinmune diseases (NEREA) from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI.
A total of 68 patients were included. FI occurred in 42 patients IR 23.5 (95% CI 19, 29.1) and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure HR 0.51 (95% CI 0.31, 0.85). Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI.
RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified.
Acute zonal occult outer retinopathy (AZOOR) is a rare syndrome characterized by sudden onset of photopsia, scotomas, and abnormal electrophysiological tests, predominantly affecting young women. ...Although its pathogenesis remains unknown, auto-reactivity to retinal components is thought to mediate tissue damage. A 42-year-old woman presented with symptoms and examination consistent with the diagnosis of AZOOR. She was treated with azathioprine for 5 years. In spite of the immunosuppressive treatment, clear progression in the visual field, autofluorescence, electrophysiological tests and optical coherence tomography was observed. Treatment with intravenous immunoglobulins (IVIg) and subcutaneous Abatacept was subsequently started with little efficacy. Hereby, we present a case of progressive AZOOR despite aggressive immunosuppression with 10-year follow up. Currently, there is no consensus regarding management of AZOOR, and the convenience of administering aggressive immunosuppression remains uncertain.
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