cDNA phage display for the discovery of theranostic autoantibodies in rheumatoid arthritis
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MECHANISM IN AUTOIMMUNITY
cDNA phage display for the discovery of theranostic autoantibodies in rheumatoid arthritis Patrick Vandormael1 • Patrick Verschueren2 • Liesbeth De Winter1 Veerle Somers1,3
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Ó Springer Science+Business Media New York 2016
Veerle Somers
Abstract Rheumatoid arthritis (RA) is the world’s most common autoimmune disease mainly characterized by a chronic inflammation of multiple synovial joints. Rheumatologists now have a whole range of treatment options including glucocorticoids (GCs), classical synthetic and biological disease-modifying antirheumatic drugs (cs- and bDMARDS), resulting in a tremendous improvement in treatment outcomes for RA patients over the last two decades. Despite this progress, the choice of treatment regimen to achieve stable remission at the individual patient level still largely depends on trial and error. In this review, the need for novel theranostic markers that can predict a patient’s response to methotrexate, the standard first-line csDMARD treatment, is discussed. Like in many autoimmune diseases, the majority of RA patients form a whole range of autoantibodies. We aim to find novel theranostic autoantibody markers using serological antigen selection, a high-throughput technique that uses cDNA phage display to identify novel antigen targets. We have constructed a barcoded cDNA phage display library from the synovial tissue of three RA patients by fusing cDNA products to the filamentous phage minor coat protein VI. This library contains a large proportion of full-length genes and gene fragments that are cloned in frame with the phage gene VI. By screening this library for antibody reactivity in serum samples of patients from the CareRA trial, which compared different intensive treatment strategies based on csDMARDs and a step-down GC schedule, our cDNA phage display library has great potential for the discovery of novel theranostic autoantibody biomarkers. Keywords Autoantibody Rheumatoid arthritis Treatment Biomarker Theranostic Phage display Abbreviations RA Rheumatoid arthritis SSc Systemic sclerosis SLE Systemic lupus erythematosus ACPA Anti-citrullinated protein antibodies CAIA Collagen antibody-induced arthritis NSAIDs Nonsteroidal anti-inflammatory drugs & Veerle Somers [email protected] 1
Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Hasselt University, Diepenbeek, Belgium
2
Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
3
Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium
DMARDs MTX GC TNF-a RF CCP UA Anti-CarP ANCA UTR
Disease-modifying anti-rheumatic drugs Methotrexate Glucocorticoids Tumor necrosis factor a Rheumatoid factor Cyclic citrullinated peptides Undifferentiated arthritis Anti-carbamylated protein Anti-neutrophil cytoplasmic antibody Untranslated region
Introduction Rheumatoid arthritis (RA) is an autoimmune disorder that mainly affects the peripheral synovial j
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