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Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classical risk factors and high disease activity.

ABSTRACT: BACKGROUND:Rheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative. METHODS:Anti-CCP2 IgG, 19 ACPA fine-specificities, IgM/IgG/IgA RF, anti-carbamylated-protein (CarP) antibodies, and 17 other autoantibodies, were analysed in 2755 RA patients and 370 controls. Antibody prevalence, levels, and co-occurrence were examined, and associations with risk factors and disease activity during 5 years were investigated for different antibody-defined RA subsets. RESULTS:Autoantibodies were detected in a substantial proportion of the traditionally defined seronegative RA subset, with ACPA fine-specificities found in 30%, IgA/IgG RF in 9.4%, and anti-CarP antibodies in 16%, with a 9.6% co-occurrence of at least two types of RA-associated autoantibodies. HLA-DRB1 shared epitope (SE) associated with the presence of ACPA in anti-CCP2-negative RA; in anti-CCP2-positive RA, the SE association was defined by six ACPA fine-specificities with high co-occurrence. Smoking associated with RF, but not with ACPA, in anti-CCP2-negative RA. Presence of ACPA and RF, but not anti-CarP antibodies, in conventionally defined "seronegative" RA, associated with worse clinical outcome. CONCLUSIONS:"Seronegative" RA is not truly a seronegative disease subset. Additional screening for ACPA fine-specificities and IgA/IgG RF defines a group of patients that resembles seropositive patients with respect to risk factors and clinical picture and may contribute to earlier diagnosis for a subset of anti-CCP2-/IgM RF- patients with a high need for active treatment.

SUBMITTER: Reed E

PROVIDER: S-EPMC7364538 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classical risk factors and high disease activity.

Reed Evan E Hedström Anna Karin AK Hansson Monika M Mathsson-Alm Linda L Brynedal Boel B Saevarsdottir Saedis S Cornillet Martin M Jakobsson Per-Johan PJ Holmdahl Rikard R Skriner Karl K Serre Guy G Alfredsson Lars L Rönnelid Johan J Lundberg Karin K

Arthritis research & therapy 20200716 1

<h4>Background</h4>Rheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibod ...[more]

PMID: 32678001

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Project description:BackgroundRheumatoid arthritis (RA)-associated lung disease (LD) associates with significantly increased morbidity and mortality. Although oxidative stress plays an important role in the inflammatory responses in other forms of lung disease, minimal work has evaluated its role in RA-LD. The current work examines the relationship between the anti-oxidant HDL-associated enzyme paraoxonase-1 (PON1), the PON1 Q192R polymorphism, and a targeted oxylipin panel with RA-LD.MethodsThis study was conducted as a retrospective chart review of a longitudinal single-center cohort of 250 RA patients. CT scans of the chest were reviewed by the interpreting radiologist and classified as small airways disease (SAD), interstitial lung disease (ILD), and bronchiectasis. PON1 activity was measured by its lactonase, arylesterase, and paraoxonase functions. The PON1 Q192R polymorphism and a targeted lipidomics panel were performed as previously reported.Results43.2% of the 250 RA patient cohort (n = 108) had available CT scans, including 48 patients (44.4%) with SAD, 27 patients (25.0%) with bronchiectasis, and 16 patients (14.8%) with ILD. Patients with SAD had significantly lower baseline PON1 activity by its arylesterase, and lactonase functions, as well as higher 15-HETE, LTB4, and PGE2 levels compared to those without SAD. These predictors of SAD remained significant after multivariate analysis including known risk factors for RA-LD. Suppressed PON1 activity also correlated with higher levels of 15-HETE and 12-HETE.ConclusionIn a single-center RA cohort, suppressed baseline PON1 activity and elevation in the oxylipins 15-HETE, LTB4, and PGE2 predicted the presence of RA-SAD in longitudinal follow-up. Key Points • Small airways disease (SAD) was present in 44.4% of this rheumatoid arthritis (RA) cohort. • Patients with SAD had significantly lower baseline PON1 activity, as well as higher levels of the oxylipins 15-HETE, LTB4, and PGE2 levels compared to those without SAD. • Further work is warranted to confirm these findings and further define the role of PON1 and lipid oxidation in RA lung disease.

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Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classical risk factors and high disease activity.

Publications

Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classical risk factors and high disease activity.

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