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

Yogan Kisten; Laurent Arnaud; Adrian Levitsky; Noémi Györi; Per Larsson; Aase Hensvold; Anca Catrina; Erik Af Klint; Hamed Rezaei

doi:10.1002/acr2.11599

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

ACR Open Rheumatol. 2023 Sep;5(9):474-480. doi: 10.1002/acr2.11599. Epub 2023 Aug 7.

Authors

Yogan Kisten¹, Laurent Arnaud², Adrian Levitsky¹, Noémi Györi¹, Per Larsson³, Aase Hensvold⁴, Anca Catrina⁴, Erik Af Klint¹, Hamed Rezaei¹

Affiliations

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

Objective: To investigate whether digital activity fluorescence optical imaging (FOI) patterns of inflammation can identify distinct rheumatoid arthritis (RA) phenotypes.

Methods: The 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).

Results: Of 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).

Conclusion: FOI-based digital quantification of hand joint inflammation revealed two distinct RA subpopulations with and without ACPA and RF related autoantibodies.