| TNF blocking therapy alters joint inflammation and hypoxia. | |
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MedLine Citation:
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PMID: 21225682 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE:: To examine the effect of TNF blocking therapy on hypoxia in vivo, macroscopic and microscopic inflammation and MR imaging. METHODS:: Inflammatory arthritis patients (n=20) underwent full clinical assessment, video-arthroscopy, synovial biopsy and magnetic resonance imaging (MRI) pre/post biologic therapy. Macroscopic synovitis/vascularity was measured by visual analogue scale (VAS) and tpO(2) was measured at arthroscopy using a LICOX probe. Cell specific markers - CD4, CD8, CD68, CD20, CD19 and blood vessel maturity were quantified by immunohistology and dual-immunofluorescent Factor VIII/αSMA staining respectively. Contiguous gadolinium-enhanced MRI of the target knee assessed synovial enhancement. RESULTS:: Biologic therapy responders, showed a significant increase of tpO(2) in vivo (p<0.05). This response is associated with significant reductions in DAS28-CRP (p=0.012), macroscopic synovitis (p=0.017), macroscopic vascularity (p=0.05), CD4(+) T-cells (p<0.041) and CD68(+) macrophages (p<0.011). Blood vessel numbers also reduced in responders, however this did not reach significance. Strong inverse correlations were demonstrated between tpO(2) and DAS28-CRP (r=-0.53, p<0.001), CD4 (r=-0.44, p<0.026), CD68 (r=-0.46 p<0.003) and macroscopic vascularity (r =-0.314, p=0.049) pre/post therapy. Furthermore, inflammation measured by MRI showed a strong inverse correlation with tpO(2) levels (r=-0.69, p<0.002) and positive correlations with CRP (r=-0.707, p=0.001), macroscopic synovitis (r=0.457, p=0.056), CD4 (r=0.553, p<0.032) and CD68 (r=0.670, p<0.002). CONCLUSION:: This is the first study to show that successful biologic therapy significantly improves in vivo synovial hypoxia. Changes are strongly associated with macro- and microscopic measures of joint inflammation and MRI improvement. This data further strengthens the concept that hypoxia is an important event driving synovial inflammation. |
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Authors:
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Aisling Kennedy Phd; Chin Teck Ng; Ting Cheng Chang; Monika Biniecka; Jacintha N O'sullivan; Eric Heffernan; Ursula Fearon; Douglas J Veale |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-10 |
Journal Detail:
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Title: Arthritis and rheumatism Volume: - ISSN: 1529-0131 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Dept. of Rheumatology, The Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Ireland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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