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Title: Novel autoantibody markers for early and seronegative rheumatoid arthritis
Authors: SOMERS, Klaartje 
Elewaut, Dirk
De Keyser, Filip
RUMMENS, Jean-Luc 
Coenen, Marieke
Blom, Marlies
SOMERS, Veerle 
Issue Date: 2011
Source: JOURNAL OF AUTOIMMUNITY, 36(1). p. 33-46
Abstract: Approximately one-third of rheumatoid arthritis (RA) patients are seronegative for the 2 serological RA markers, rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (ACCP). Moreover, the sensitivities of both markers are lower in the diagnostically important early disease phase. The aim of this study was to identify additional autoantibody markers for early RA and for RF-negative, ACCP-negative (seronegative) RA. We screened an RA synovium cDNA phage display library with autoantibodies in plasma from 10 early (symptoms of maximum 1 year) and 10 seronegative (RF-negative, ACCP-negative) RA patients with validation in 72 additional RA patients and 121 controls (38 healthy controls, 43 patients with other inflammatory rheumatic diseases, 20 osteoarthritis patients and 20 subjects with mechanical joint complaints). Fourteen novel autoantibodies were identified that showed a 54% sensitivity and 90% specificity for RA. For 11 of these autoantibodies, an exclusive presence was demonstrated in RA patients (100% specificity, 37% sensitivity) as compared to controls. All early RA patients were positive for at least one of the identified autoantibodies and antibody-positivity was associated with a shorter disease duration (P = 0.0087). 52% of RA patients who initially tested negative for RF and ACCP, tested positive for at least one of the 14 novel autoantibodies, resulting in a 19% increase in sensitivity compared to current serological testing. Moreover, 5 identified autoantibodies were detected more frequently in seronegative RA patients, indicating that these autoantibodies constitute novel candidate markers for this RA subtype. We demonstrated that the targets of 3 of these 5 autoantibodies had an increased expression in RA synovial tissue compared to control synovial tissue. pointing towards a biological rationale for these auto antibody targets in RA. In conclusion, we identified novel candidate autoantibody markers for RA that can be detected in early and seronegative RA patients indicating the potential added value for RA diagnostics. (C) 2010 Elsevier Ltd. All rights reserved.
Notes: [Somers, Klaartje; Geusens, Piet; Stinissen, Piet; Somers, Veerle] Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium. [Somers, Klaartje; Geusens, Piet; Stinissen, Piet; Somers, Veerle] Transnat Univ Limburg, Sch Life Sci, B-3590 Diepenbeek, Belgium. [Geusens, Piet] Maastricht Univ, Med Ctr, Dept Internal Med Rheumatol, NL-6202 AZ Maastricht, Netherlands. [Elewaut, Dirk; De Keyser, Filip] Ghent Univ Hosp, Div Rheumatol, B-9000 Ghent, Belgium. [Rummens, Jean-Luc] Jessa Hosp, Clin Lab Expt Hematol, B-3500 Hasselt, Belgium. [Coenen, Marieke] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Blom, Marlies] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Rheumatol, NL-6500 HB Nijmegen, Netherlands.
Keywords: Rheumatoid arthritis; Seronegative; Anti-CCP antibodies; Autoantibodies; Disease markers
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ISSN: 0896-8411
e-ISSN: 1095-9157
DOI: 10.1016/j.jaut.2010.10.003
ISI #: 000287832500006
Category: A1
Type: Journal Contribution
Validations: ecoom 2012
Appears in Collections:Research publications

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