Prostaglandin E2 Synthesizing Enzymes in Rheumatoid Arthritis B Cells and the Effects of B Cell Depleting Therapy on Enzyme Expression

Introduction: B cells may play an important role in promoting immune activation in the rheumatoid synovium and can produce prostaglandin E-2 (PGE(2)) when activated. In its turn, PGE(2) formed by cyclooxygenase (COX) and microsomal prostaglandin E-2 synthase 1 (MPGES1) contributes to the rheumatoid arthritis (RA) pathological process. Therapeutic depletion of B cells results in important improvement in controlling disease activity in rheumatoid patients. Therefore we investigated the expression of PGE(2) pathway enzymes in RA B cells and evaluated the effects of B cell depleting therapy on their expression in RA tissue. Methods: B cells expressing MPGES1 and COX-2 were identified by flow cytometry in in vitro stimulated and control mononuclear cells isolated from synovial fluid and peripheral blood of RA patients. Synovial biopsies were obtained from 24 RA patients before and at two consecutive time points after rituximab therapy. Expression of MPGES1, COX-1 and COX-2, as well as interleukin (IL)-1 beta and IL-6, known inducers of MPGES1, was quantified in immunostained biopsy sections using computerized image analysis. Results: Expression of MPGES1 or COX-2 was significantly upregulated upon stimulation of B cells from blood and synovial fluid while control cells displayed no detectable enzymes. In synovial biopsy sections, the expression of MPGES1, COX-1 or COX-2 was resistant to rituximab therapy at 8 or 16 weeks after start of treatment. Furthermore expression of IL-1 beta in the synovial tissue remained unchanged, while IL-6 tended to decrease after therapy. Conclusions: Therapy with B cell depleting agents, although efficient in achieving good clinical and radiographic response in RA patients, leaves important inflammatory pathways in the rheumatoid synovium essentially unaffecte

Semitic Dialects and Dialectology

Characterised by the multiplicity and diversity of research and methodology, the European tradition of Semitic linguistics has always supported fieldwork and highly valued the data obtained in this way as it allows to create an interesting dynamic for linguistic studies itself. In the spirit of this tradition and to uphold it, the present book is a collection of articles based on data gathered primarily during field research expeditions. The volume is divided into two parts—Studies on various specific linguistic issues and Texts containing previously unpublished transcriptions of audio recordings in Arabic dialects, Maltese and Jibbali/Shehret.Die europäische Tradition der semitischen Linguistik, die sich durch Vielfalt der Forschungsmethoden auszeichnet, hat dialektologische Feldforschung immer hoch geschätzt, da die gewonnenen Sprachaufnahmen im Kontext der älteren Sprachformen gesetzt werden und somit eine hochgradig interessante Dynamik in der Sprachwissenschaft ermöglichen. Im Geiste dieser Tradition und um sie aufrechtzuerhalten, ist das vorliegende Buch eine Sammlung von Artikeln, deren Daten vor allem während der Feldforschung gesammelt wurden. Der Band gliedert sich in zwei Teile - Studien zu verschiedenen spezifischen linguistischen Fragestellungen und Texte mit bisher unveröffentlichten Transkriptionen von Audioaufnahmen in arabischen Dialekten, Maltesisch und Jibbali/Shehret

Semitic Dialects and Dialectology

Characterised by the multiplicity and diversity of research and methodology, the European tradition of Semitic linguistics has always supported fieldwork and highly valued the data obtained in this way as it allows to create an interesting dynamic for linguistic studies itself. In the spirit of this tradition and to uphold it, the present book is a collection of articles based on data gathered primarily during field research expeditions. The volume is divided into two parts—Studies on various specific linguistic issues and Texts containing previously unpublished transcriptions of audio recordings in Arabic dialects, Maltese and Jibbali/Shehret

Benefit of anti-TNF therapy in rheumatoid arthritis patients with moderate disease activity

Objectives. Anti-TNF therapy has improved outcomes for patients with highly active RA. Less is known about its effectiveness in patients with lower disease activity. The aim of this analysis is to compare the response to anti-TNF therapy between RA patients with high (DAS28 > 5.1) and moderate (DAS28 > 3.2–5.1) disease activity. Methods. A total of 4687 anti-TNF and 344 DMARD patients with high disease activity despite treatment with two standard DMARDs (including MTX) and 224 anti-TNF- and 300 DMARD-treated patients with moderate disease activity were selected from the British Society For Rheumatology Biologics Register. Mean change in HAQ over the first 12 months of enrolment was compared first between anti-TNF-treated and untreated patients in each DAS28 group, and then between anti-TNF-treated patients in the moderate and high DAS28 groups, using doubly robust estimates, adjusting for age, gender, disease duration, baseline HAQ and DAS28 score, number of previous DMARDs and steroid use. Results. Compared with anti-TNF-untreated patients within each DAS group, treated patients were younger, had higher DAS28 and HAQ and had failed a higher number of previous DMARDs. The mean adjusted change in HAQ over 12 months was similar in anti-TNF-treated patients with moderate and high disease activity at baseline: moderate −0.26 (95% CI −0.35, −0.16), high −0.28 (95% CI −0.34, −0.23) and mean difference −0.03 (95% CI −0.14, 0.08). Conclusions. Improvement in HAQ score 12 months after start of anti-TNF therapy was not dependent on baseline DAS28 scores, suggesting that substantial benefits may also be gained by treating those with moderately active disease despite standard DMARD therapy