Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid Arthritis

Author:

Kisten Yogan1ORCID,Arnaud Laurent2ORCID,Levitsky Adrian1,Györi Noémi1,Larsson Per3,Hensvold Aase4ORCID,Catrina Anca4,af Klint Erik1,Rezaei Hamed1

Affiliation:

1. Karolinska Institute and Karolinska University Hospital Stockholm Sweden

2. Hôpitaux Universitaires de Strasbourg Service de Rhumatologie National Reference Center for Rare Systemic Autoimmune Diseases Strasbourg Alsace‐Champagne‐Ardenne France

3. Academic Specialist Center Stockholm Sweden

4. Karolinska Institute and Karolinska University Hospital and Academic Specialist Center Stockholm Sweden

Abstract

ObjectiveTo investigate whether digital activity fluorescence optical imaging (FOI) patterns of inflammation can identify distinct rheumatoid arthritis (RA) phenotypes.MethodsThe hands of newly diagnosed patients with RA were evaluated by clinical examination, musculoskeletal ultrasound, and FOI. Inflammation on FOI was defined when capillary leakage and/or fluorophore perfusion was present. The FOI composite image was quantified into a digital disease activity (DACT) score, using novel computerized algorithms. Unsupervised clustering on FOI inflammatory patterns was used to identify subgroups of patients relative to anticyclic citrullinated peptides (ACPA) and/or rheumatoid factor (RF).ResultsOf 1326 examined hand joints in 39 patients with RA (72% female; 56% ever‐smokers; 54% RF positive and 69% ACPA positive), 400 (30%) showed inflammation by FOI, and 95% (37 of 39) of patients had DACT‐FOI scores greater than 1. Unsupervised analysis on FOI patterns revealed two patient clusters, cluster 1 (n = 29) and cluster 2 (n = 10). The proportion of seropositive patients was significantly higher in cluster 1 versus cluster 2 (90%, 26 of 29 vs. 30%, 3 of 10; P < 0.01), whereas C‐reactive‐protein levels (minimum‐maximum) were significantly higher in cluster 2 (20 mg/l [1‐102]) versus cluster 1 (2 mg/l [0‐119]; P = 0.01). A wider variety and proportion of inflamed joints emerged for patients with RA in cluster 2 versus cluster 1, in which inflammation was more concentrated around the wrists and the right metacarpophalangeal 2 (MCP2), bilateral MCP3, and, to a lesser degree, left MCP2 and proximal interphalangeal joint and tendon regions. Cluster 1 displayed lower mean (±SD) DACT scores compared with cluster 2 (3.6 ± 2.1 vs. 5.4 ± 2.1; P = 0.03).ConclusionFOI‐based digital quantification of hand joint inflammation revealed two distinct RA subpopulations with and without ACPA and RF related autoantibodies.

Publisher

Wiley

Subject

Rheumatology

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