Rheumatoid Arthritis: Ding T

Smith N, Ding T, Butt S, Gadsby K, Deighton C. · Department of Rheumatology, Derbyshire Royal Infirmary, London Road, Derby, DE1 2QY, UK. · Rheumatology (Oxford). · Pubmed #18603597 No free full text.

Abstract: OBJECTIVES: The NICE re-appraisal of anti-TNF requires demonstration of ongoing response, making the baseline 28-joint Disease Activity Score (DAS28) crucially important. A retrospective analysis of all RA patients on their first anti-TNF determined predictive factors for those classified as non-responders at 6 months according to current NICE guidelines. METHODS: The patients were divided into responders (DAS28 dropped by >1.2) and non-responders. These groups were compared for demographics, DAS28 at the two pre-assessments 1 month apart and at baseline. Exposure to intramuscular, oral and IA steroids in the 3 months period before the baseline DAS28 was recorded. RESULTS: At 6-month assessment in 256 patients, 82.8% were responders with no demographic differences between them and non-responders. Although the first pre-assessment score was not significantly different (6.8 vs 6.6), the second pre-assessment score (7.1 vs 6.7) and the baseline DAS (7.2 vs 6.3) were lower in the non-responders (P < 0.04 and P < 0.001, respectively). Comparing the differences in DAS28 from the first pre-assessment to baseline, the responders had increased by 0.4, and the non-responders had decreased by 0.4, (P < 0.001). If the first pre-assessment score had been taken as the baseline DAS28, then 9.4% of responders would be re-classified as non-responders, and 31.8% of non-responders would be re-classified as responders. The proportion of patients who had steroid treatment within the 3 months period before the baseline DAS28 did not differ significantly between the responders and non-responders (34% vs 41%, P = 0.38). CONCLUSION: Baseline DAS28 is critical in classifying responders at the 6-month assessment.

Ding T, Roddy E, Pande I. · Department of Rheumatology Nottingham University Hospitals NHS Trust, Nottingham NG7, 2UH, UK. · Rheumatology (Oxford). · Pubmed #18375973 No free full text.

This publication has no abstract.

Ding T, Hall A, Jacobs K, David J. · Department of Rheumatology, Nuffield Orthopaedic Centre, Oxford, UK. · Rheumatology (Oxford). · Pubmed #18356173 No free full text.

Abstract: OBJECTIVES: This study investigates the psychological functioning of children with polyarticular joint disease and its association with disease activity and disability. METHODS: Sixty children aged 7-18 yrs with juvenile idiopathic arthritis and >4 joints involved were recruited. Children underwent a physical examination. The Childhood HAQ was completed by both the children and their parents. Children also completed questionnaires for depression (Birleson Depression Inventory; BDI), anxiety (Revised Children's Manifest Anxiety Scale; RCMAS) and peer, emotional and behavioural problems (Strengths and Difficulties Questionnaire; SDQ). Clinical information was extracted from the hospital records. RESULTS: Self-reported psychological functioning (depression, anxiety, and behaviour) was not different from the normal population. Parent-reported emotional difficulties on the SDQ were somewhat elevated. There were no significant correlations between psychological functioning and physician-rated disease activity score or the number of active joints at the time of assessment. Furthermore, no differences in psychological functioning were found between children with or without significantly raised inflammatory markers. All aspects of psychological function (depression, anxiety and behaviour) correlated moderately with physical function (r(s) = 0.49, 0.41, 0.46, respectively; all P < 0.01). CONCLUSIONS: Children and adolescents with polyarthritis are not at significantly elevated risk of psychological difficulties. Poor psychological outcome was associated with more severe physical disability but not with the level of disease activity.

Zhang W, Ding T, Zhang J, Su J, Yu J, Li J, Li F, Wang C, Liu N, Liu X, Ma W, Yao L. · Department of Microbiology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China. · J Cell Biochem. · Pubmed #17427955 No free full text.

Abstract: Discoidin domain receptor 2 (DDR2) is a kind of protein tyrosine kinases associated with cell proliferation and tumor metastasis, and collagen, a ligand for DDR2, up-regulates matrix metalloproteinase 1 (MMP-1) and MMP-2 expression in extracellular matrix (ECM). To investigate the role of DDR2 in cartilage destruction in rheumatoid arthritis (RA), we expressed the extracellular domain (ECD) of DDR2 (without signal peptide and transmembrane domain, designated DR) in insect cells, purified and characterized DR, hoping to use it as a specific antagonist of DDR2. By using Bac-To-Bac Expression System with a His tag, we successfully obtained the recombinant bacularvirus containing DDR2 ECD, purified it and characterized its function. The soluble fraction of DR was about 12% of the total fused protein. After chromatographic purification, DR with 92% purity was obtained. Competitive inhibition assay demonstrated that DR blocked the binding between DDR2 and natural DDR2 receptors on NIH3T3 and synovial cells. Results of RT-PCR, Western blotting, and gelatinase zymography showed that DR was capable of inhibiting MMP-1 and MMP-2 secretion from NIH3T3 and RA synoviocytes stimulated by collagen II. For MMP-1, inhibition was displayed at the levels of mRNA and protein, whereas for MMP-2 it was at the level of protein. These findings suggested that the expressed DR inhibited the activity of natural DDR2 and relevant MMP-1 and MMP-2 expression in RA synoviocytes and NIH3T3 cells provoked by collagen II.

Zhang W, Ding T, Zhang J, Su J, Li F, Liu X, Ma W, Yao L. · Department of Microbiology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China. · Mol Cell Biochem. · Pubmed #16967187 No free full text.

Abstract: Discoidin domain receptor 2 (DDR2) is a kind of protein tyrosine kinases associated with cell proliferation and tumor metastasis, and collagen, identified as a ligand for DDR2, up-regulates matrix metallloproteinase 1 (MMP-1) and MMP-2 expression in cellular matrix. To investigate the roles of DDR2 in destruction of cartilage in rheumatoid arthritis (RA) and tumor metastasis, we tried to express extracellular domain of DDR2 fused with a His tag to increase protein solubility and facilitate purification (without signal peptide and transmembrane domain, designated DR) in Pichia pastoris, purify the expressed protein, and characterize its function, for purpose of future application as a specific DDR2 antagonist. Two clones of relative high expression of His-DR were obtained. After purification by a Ni-NTA (nitric-tri-acetic acid) chromatographic column, soluble fused His-DR over 90% purity were obtained. Competitive binding inhibition assay demonstrated that expressed His-DR could block the binding of DDR2 and natural DDR2 receptors on NIT3T3 and synovial cell surfaces. Results of RT-PCR, Western blotting, and gelatinase zymography showed that His-DR was capable of inhibiting MMP-1 and MMP-2 secretion from NIT3T3 cells and RA synoviocytes stimulated by collagen II. For MMP-1, the inhibitory effect was displayed at the levels of mRNA and protein, whereas for MMP-2 it was demonstrated at the level of protein physiological activity. All these findings suggested that the fused expressed His-DR inhibited the activity of natural DDR2, and relevant MMP-1 and MMP-2 expression in synoviocytes and NIH3T3 cells provoked by collagen II.