Antibodies Against Three Novel Peptides in Early Axial Spondyloarthritis Patients From Two Independent Cohorts

被引：14

作者：

Quaden, Dana ^{[1
]}

Vandormael, Patrick ^{[1
]}

Ruytinx, Pieter ^{[1
]}

Geusens, Piet ^{[1
,2
,3
]}

Corten, Kristoff ^{[4
]}

Vanhoof, Johan ^{[2
]}

Liesenborgs, Jori ^{[1
,5
]}

van Reeth, Frank ^{[1
,5
]}

Agten, Anouk ^{[1
]}

Vandenabeele, Frank ^{[1
]}

de Vlam, Kurt ^{[6
]}

Somers, Veerle ^{[1
]}

机构：

[1] Hasselt Univ, Hasselt, Belgium

[2] ReumaClin, Genk, Belgium

[3] Maastricht Univ, Med Ctr, Maastricht, Netherlands

[4] Ziekenhuis Oost Limburg, Genk, Belgium

[5] Flanders Make, Hasselt, Belgium

[6] Univ Hosp Leuven, Leuven, Belgium

来源：

ARTHRITIS & RHEUMATOLOGY | 2020年 / 72卷 / 12期

关键词：

SOCIETY CLASSIFICATION CRITERIA; CDNA PHAGE DISPLAY; ANKYLOSING-SPONDYLITIS; HUMAN BETA-DEFENSIN-3; AUTOANTIBODIES; OPTIMIZATION; DISCOVERY; DIAGNOSIS; DUX4;

D O I：

10.1002/art.41427

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective This study was undertaken to identify novel autoantibodies in axial spondyloarthritis (SpA) and determine their diagnostic potential in patients with early axial SpA and controls from 2 independent cohorts. Methods An axial SpA complementary DNA phage display library was used to screen for novel IgG antibodies in plasma from patients with early axial SpA. The presence of these antibodies against novel peptides (i.e., peptides identified in an early axial SpA cohort from Hasselt University, designated UH-axSpA) was determined by enzyme-linked immunosorbent assay in 76 patients with early axial SpA, 75 controls with nonspecific chronic low back pain, 60 patients with rheumatoid arthritis, and 94 healthy controls from the UH cohort. Antibody reactivity to these novel peptides was further validated in 174 patients with axial SpA (of whom 79 had early axial SpA) from the University Hospitals Leuven (Bio)SPAR (Spondyloarthritis [Biologics]) cohort. Results We identified antibodies to 9 novel UH-axSpA peptides, corresponding to randomly formed peptides and to a novel axial SpA autoantigen, double homeobox protein 4. Antibodies to 3 UH-axSpA peptides with the highest positive likelihood ratio (LR) for a diagnosis of axial SpA were present in significantly more patients with early axial SpA from the UH and (Bio)SPAR cohorts (14.2% [22/155]) compared to controls with chronic low back pain (5% [4/75]), resulting in 95% specificity. The positive LR for confirming axial SpA using antibodies to these 3 UH-axSpA peptides was 2.7, which is higher than the LR obtained with the currently used laboratory marker C-reactive protein. Testing for antibodies to these 3 UH-axSpA peptides in patients with chronic low back pain increased the posttest probability of a diagnosis of axial SpA from 79% to 91%. Conclusion Antibodies to 3 UH-axSpA peptides could provide a novel tool in the diagnosis of a subset of axial SpA patients.

引用

页码：2094 / 2105

页数：12

共 39 条

[1] Chapter 4 - European guidelines for the management of chronic nonspecific low back pain [J].

Airaksinen, O. ;

Brox, J. I. ;

Cedraschi, C. ;

Hildebrandt, J. ;

Klaber-Moffett, J. ;

Kovacs, F. ;

Mannion, A. F. ;

Reis, S. ;

Staal, J. B. ;

Ursin, H. ;

Zanoli, G. .

EUROPEAN SPINE JOURNAL, 2006, 15 (Suppl 2) :S192-S300

[2] THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].

ARNETT, FC ;

EDWORTHY, SM ;

BLOCH, DA ;

MCSHANE, DJ ;

FRIES, JF ;

COOPER, NS ;

HEALEY, LA ;

KAPLAN, SR ;

LIANG, MH ;

LUTHRA, HS ;

MEDSGER, TA ;

MITCHELL, DM ;

NEUSTADT, DH ;

PINALS, RS ;

SCHALLER, JG ;

SHARP, JT ;

WILDER, RL ;

HUNDER, GG .

ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324

[3] Diagnostic delay in axial spondyloarthritis: A cross-sectional study of 432 patients [J].

Behar, Vanina Masson ;

Dougados, Maxime ;

Etcheto, Adrien ;

Kreis, Sarah ;

Fabre, Stephanie ;

Hudry, Christophe ;

Dadoun, Sabrina ;

Rein, Christopher ;

Pertuiset, Edouard ;

Fautrel, Bruno ;

Gossec, Laure .

JOINT BONE SPINE, 2017, 84 (04) :467-471

[4]

CALIN A, 1994, J RHEUMATOL, V21, P2281

[5] BLAST plus : architecture and applications [J].

Camacho, Christiam ;

Coulouris, George ;

Avagyan, Vahram ;

Ma, Ning ;

Papadopoulos, Jason ;

Bealer, Kevin ;

Madden, Thomas L. .

BMC BIOINFORMATICS, 2009, 10

[6] DUX4 Suppresses MHC Class I to Promote Cancer Immune Evasion and Resistance to Checkpoint Blockade [J].

Chew, Guo-Liang ;

Campbell, Amy E. ;

De Neef, Emma ;

Sutliff, Nicholas A. ;

Shadle, Sean C. ;

Tapscott, Stephen J. ;

Bradley, Robert K. .

DEVELOPMENTAL CELL, 2019, 50 (05) :658-+

[7] Biopython']python: freely available Python']Python tools for computational molecular biology and bioinformatics [J].

Cock, Peter J. A. ;

Antao, Tiago ;

Chang, Jeffrey T. ;

Chapman, Brad A. ;

Cox, Cymon J. ;

Dalke, Andrew ;

Friedberg, Iddo ;

Hamelryck, Thomas ;

Kauff, Frank ;

Wilczynski, Bartek ;

de Hoon, Michiel J. L. .

BIOINFORMATICS, 2009, 25 (11) :1422-1423

[8] Soluble and Tissue Biomarkers in Ankylosing Spondylitis [J].

de Vlam, Kurt .

BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY, 2010, 24 (05) :671-682

[9] Magnetic Resonance Imaging of the Sacroiliac Joints Indicating Sacroiliitis According to the Assessment of SpondyloArthritis international Society Definition in Healthy Individuals, Runners, and Women With Postpartum Back Pain [J].

de Winter, Janneke ;

de Hooge, Manouk ;

van de Sande, Marleen ;

de Jong, Henriette ;

van Hoeven, Lonneke ;

de Koning, Anoek ;

Berg, Inger Jorid ;

Ramonda, Roberta ;

Baeten, Dominique ;

van der Heijde, Desiree ;

Weel, Angelique ;

Landewe, Robert .

ARTHRITIS & RHEUMATOLOGY, 2018, 70 (07) :1042-1048

[10] Autoantibodies to two novel peptides in seronegative and early rheumatoid arthritis [J].

De Winter, Liesbeth M. ;

Hansen, Wendy L. J. ;

van Steenbergen, Hanna W. ;

Geusens, Piet ;

Lenaerts, Jan ;

Somers, Klaartje ;

Stinissen, Piet ;

van der Helm-van Mil, Annette H. M. ;

Somers, Veerle .

RHEUMATOLOGY, 2016, 55 (08) :1431-1436

← 1 2 3 4 →