Identification of a transitional fibroblast function in very early rheumatoid arthritis.

OBJECTIVES: Synovial fibroblasts actively regulate the inflammatory infiltrate by communicating with neighbouring endothelial cells (EC). Surprisingly, little is known about how the development of rheumatoid arthritis (RA) alters these immunomodulatory properties. We examined the effects of phase of RA and disease outcome (resolving vs persistence) on fibroblast crosstalk with EC and regulation of lymphocyte recruitment. METHODS: Fibroblasts were isolated from patients without synovitis, with resolving arthritis, very early RA (VeRA; symptom ≤12 weeks) and established RA undergoing joint replacement (JRep) surgery. Endothelial-fibroblast cocultures were formed on opposite sides of porous filters. Lymphocyte adhesion from flow, secretion of soluble mediators and interleukin 6 (IL-6) signalling were assessed. RESULTS: Fibroblasts from non-inflamed and resolving arthritis were immunosuppressive, inhibiting lymphocyte recruitment to cytokine-treated endothelium. This effect was lost very early in the development of RA, such that fibroblasts no longer suppressed recruitment. Changes in IL-6 and transforming growth factor beta 1 (TGF-ß1) signalling appeared critical for the loss of the immunosuppressive phenotype. In the absence of exogenous cytokines, JRep, but not VeRA, fibroblasts activated endothelium to support lymphocyte. CONCLUSIONS: In RA, fibroblasts undergo two distinct changes in function: first a loss of immunosuppressive responses early in disease development, followed by the later acquisition of a stimulatory phenotype. Fibroblasts exhibit a transitional functional phenotype during the first 3 months of symptoms that contributes to the accumulation of persistent infiltrates. Finally, the role of IL-6 and TGF-ß1 changes from immunosuppressive in resolving arthritis to stimulatory very early in the development of RA. Early interventions targeting 'pathogenic' fibroblasts may be required in order to restore protective regulatory processes.

The patient's role in the assessment of students' communication skills.

The central focus of this study was to investigate the effects of the introduction of a new system of formative assessment on students' perceptions of their communication skills, by recruiting patients to assess the student who provided their treatment on that day. The assessment tool detailed 12 aspects of communication and the patient 'scored' the student from 0 (representing very poor skills) to 10 (representing excellence). The patients then handed the completed form at the end of the treatment session to the student. This would then form part of their clinical portfolio for reflection and consideration. A pilot scheme was implemented with the consent of staff, students and patients. Minor adjustments were made to the forms to clarify more precisely the point for assessment. The communication visual analogue scale demonstrated a perceived improvement over the ten-week period 86.4% for the experienced students and 80% for the novice students. The students who were interviewed all stated that they were comfortable with the patients assessing them and for some it made them feel more confident. Some students were surprised by the marks that the patients gave on some aspects of their communication, particularly pertaining to maintaining eye contact.