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

Dana Quaden; Patrick Vandormael; Pieter Ruytinx; Piet Geusens; Kristoff Corten; Johan Vanhoof; Jori Liesenborgs; Frank van Reeth; Anouk Agten; Frank Vandenabeele; Kurt de Vlam; Veerle Somers

doi:10.1002/art.41427

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

Dana Quaden, Patrick Vandormael, Pieter Ruytinx, Piet Geusens, Kristoff Corten, Johan Vanhoof, Jori Liesenborgs, Frank van Reeth, Anouk Agten, Frank Vandenabeele, Kurt de Vlam, Veerle Somers^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

7 Citations (Web of Science)

Abstract

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.

Original language	English
Pages (from-to)	2094-2105
Number of pages	12
Journal	Arthritis & Rheumatology
Volume	72
Issue number	12
Early online date	4 Nov 2020
DOIs	https://doi.org/10.1002/art.41427
Publication status	Published - Dec 2020

Keywords

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

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10.1002/art.41427

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@article{1c907d09f0c64c1581c96213b71e0e3c,

title = "Antibodies Against Three Novel Peptides in Early Axial Spondyloarthritis Patients From Two Independent Cohorts",

abstract = "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.",

keywords = "SOCIETY CLASSIFICATION CRITERIA, CDNA PHAGE DISPLAY, ANKYLOSING-SPONDYLITIS, HUMAN BETA-DEFENSIN-3, AUTOANTIBODIES, OPTIMIZATION, DISCOVERY, DIAGNOSIS, DUX4",

author = "Dana Quaden and Patrick Vandormael and Pieter Ruytinx and Piet Geusens and Kristoff Corten and Johan Vanhoof and Jori Liesenborgs and {van Reeth}, Frank and Anouk Agten and Frank Vandenabeele and {de Vlam}, Kurt and Veerle Somers",

year = "2020",

month = dec,

doi = "10.1002/art.41427",

language = "English",

volume = "72",

pages = "2094--2105",

journal = "Arthritis & Rheumatology",

issn = "2326-5191",

publisher = "Wiley",

number = "12",

}

TY - JOUR

T1 - Antibodies Against Three Novel Peptides in Early Axial Spondyloarthritis Patients From Two Independent Cohorts

AU - Quaden, Dana

AU - Vandormael, Patrick

AU - Ruytinx, Pieter

AU - Geusens, Piet

AU - Corten, Kristoff

AU - Vanhoof, Johan

AU - Liesenborgs, Jori

AU - van Reeth, Frank

AU - Agten, Anouk

AU - Vandenabeele, Frank

AU - de Vlam, Kurt

AU - Somers, Veerle

PY - 2020/12

Y1 - 2020/12

N2 - 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.

AB - 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.

KW - SOCIETY CLASSIFICATION CRITERIA

KW - CDNA PHAGE DISPLAY

KW - ANKYLOSING-SPONDYLITIS

KW - HUMAN BETA-DEFENSIN-3

KW - AUTOANTIBODIES

KW - OPTIMIZATION

KW - DISCOVERY

KW - DIAGNOSIS

KW - DUX4

U2 - 10.1002/art.41427

DO - 10.1002/art.41427

M3 - Article

C2 - 32638516

SN - 2326-5191

VL - 72

SP - 2094

EP - 2105

JO - Arthritis & Rheumatology

JF - Arthritis & Rheumatology

IS - 12

ER -