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Identification and evaluation of novel synovial tissue biomarkers in rheumatoid arthritis by laser scanning cytometry.
MedLine Citation:
PMID:  22251373     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ABSTRACT: INTRODUCTION: Suitable biomarkers are essential for therapeutic strategies in personalised medicine in terms of diagnosis as well as prognosis. With highly specific biomarkers, it is possible to e.g. identify patients with poor prognosis which enables early intervention and intensive treatment. The aim of this study was to identify and validate biomarkers and possible combinations for a perspective use in immunoscintigraphy, which may improve diagnosis of rheumatoid arthritis (RA) patients with consideration of inflammatory activity in the affected joints. Therefore, we tested several monoclonal antibodies (mAb) directed against cellular surface molecules on cells likely to be involved in the pathogenesis of RA. METHODS: Synovial tissue from patients with long-standing RA (accompanied by synovitis with varying states of current activity) and patients with acute non-RA-arthritis were stained for surface molecules on different cell types using fluorochrome-labelled antibodies. Tissue analysis was done by laser scanning cytometry (LSC), statistical evaluation by discriminant analysis and ROC analysis. RESULTS: CD11b, HLA-DR, CD90, and CD64 revealed significant differences between tissues from patients with RA and acute non-RA-arthritis. Especially with the expression of CD64, both patient cohorts could be discriminated with high sensitivity and specificity. RA classification was improved by simultaneously investigating the expression of two or three different surface proteins such as HLA-DR, CD90 and CD29 in the tissue. The simultaneous analysis of CD64 together with CD304 or the combination of CD11b and CD38 were suitable for the identification of RA patients with high current activity in synovitis. CONCLUSIONS: In this study we show that LSC is a novel reliable method in biomarker pre-validation in RA. Hence, here identified mAbs in-situ may allow their potential use in in-vivo approaches. Moreover we could prove that biomarker combination analysis resulted in better discrimination than single marker analysis. Combinations of these markers are a novel and reliable panel for the discrimination between RA and acute non-RA-arthritis. In addition, further expedient combinations may be novel promising biomarker panels to identify current activity in synovitis in RA.
Authors:
Christiane Fueldner; Anja Mittag; Jens Knauer; Maria Biskop; Pierre Hepp; Roger Scholz; Ulf Wagner; Ulrich Sack; Frank Emmrich; Attila Tarnok; Joerg Lehmann
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-17
Journal Detail:
Title:  Arthritis research & therapy     Volume:  14     ISSN:  1478-6362     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101154438     Medline TA:  Arthritis Res Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  R8     Citation Subset:  -    
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