Autoantibodies to two novel peptides in seronegative and early rheumatoid arthritis.
Despite recent progress in biomarker discovery for RA diagnostics, still over one-third of RA patients-and even more in early disease-present without RF or ACPA. The aim of this study was to confirm the presence of previously identified autoantibodies to novel Hasselt University (UH) peptides in early and seronegative RA.



Screening for antibodies against novel UH peptides UH-RA.1, UH-RA.9, UH-RA.14 and UH-RA.21, was performed in two large independent cohorts. Peptide ELISAs were developed to screen for the presence of antibodies to UH-RA peptides. First, 292 RA patients (including 39 early patients), 90 rheumatic and 97 healthy controls from UH were studied. Antibody reactivity to two peptides (UH-RA.1 and UH-RA.21) was also evaluated in 600 RA patients, 309 patients with undifferentiated arthritis and 157 rheumatic controls from the Leiden Early Arthritis Clinic cohort.



In both cohorts, 38% of RA patients were seronegative for RF and ACPA. Testing for autoantibodies to UH-RA.1 and UH-RA.21 reduced the serological gap from 38% to 29% in the UH cohort (P = 0.03) and from 38% to 32% in the Leiden Early Arthritis Clinic cohort (P = 0.01). Furthermore, 19-33% of early RA patients carried antibodies to these peptides. Specificities in rheumatic controls ranged from 82 to 96%. Whereas antibodies against UH-RA.1 were related to remission, anti-UH-RA.21 antibodies were associated with inflammation, joint erosion and higher tender and swollen joint counts.



This study validates the presence of antibody reactivity to novel UH-RA peptides in seronegative and early RA. This might reinforce current diagnostics and improve early diagnosis and intervention in RA.
Hasselt University, Biomedical Research Institute, and transnationale Universiteit Limburg, School of Life Sciences, Hasselt, Belgium.
Liesbeth M
LM
De Winter
Hasselt University, Biomedical Research Institute, and transnationale Universiteit Limburg, School of Life Sciences, Hasselt, Belgium.
Wendy L J
WL
Hansen
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Hanna W
HW
van Steenbergen
Hasselt University, Biomedical Research Institute, and transnationale Universiteit Limburg, School of Life Sciences, Hasselt, Belgium Department of Rheumatology, Reuma Clinic, Genk, Belgium Rheumatology, Maastricht University Medical Center, Maastricht, The Netherlands.
Piet
P
Geusens
Department of Rheumatology, Reuma Instituut Department of Rheumatology, Jessa Hospitals, Hasselt, Belgium.
Jan
J
Lenaerts
Hasselt University, Biomedical Research Institute, and transnationale Universiteit Limburg, School of Life Sciences, Hasselt, Belgium.
Klaartje
K
Somers
Hasselt University, Biomedical Research Institute, and transnationale Universiteit Limburg, School of Life Sciences, Hasselt, Belgium.
Piet
P
Stinissen
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Annette H M
AH
van der Helm-van Mil
Hasselt University, Biomedical Research Institute, and transnationale Universiteit Limburg, School of Life Sciences, Hasselt, Belgium veerle.somers@uhasselt.be.
Veerle
V
Somers
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology*; D010456:Peptides, Cyclic / Q000378:metabolism; D011379:Prognosis; D012217:Rheumatoid Factor / Q000378:metabolism
D001323:Autoantibodies; D015415:Biomarkers; D010455:Peptides; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor
anti-citrullinated protein antibodies; autoantibodies; biomarkers; diagnosis; early disease; rheumatoid arthritis; rheumatoid factor; serological gap; seronegative