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

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....

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Main Authors: Yogan Kisten, Laurent Arnaud, Adrian Levitsky, Noémi Györi, Per Larsson, Aase Hensvold, Anca Catrina, Erik af Klint, Hamed Rezaei
Format: Article
Language:English
Published: Wiley 2023-09-01
Series:ACR Open Rheumatology
Online Access:https://doi.org/10.1002/acr2.11599
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author Yogan Kisten
Laurent Arnaud
Adrian Levitsky
Noémi Györi
Per Larsson
Aase Hensvold
Anca Catrina
Erik af Klint
Hamed Rezaei
author_facet Yogan Kisten
Laurent Arnaud
Adrian Levitsky
Noémi Györi
Per Larsson
Aase Hensvold
Anca Catrina
Erik af Klint
Hamed Rezaei
author_sort Yogan Kisten
collection DOAJ
description 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.
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spelling doaj.art-9c4bcc59d748443eb8094a9afe40ce8d2023-09-15T09:36:43ZengWileyACR Open Rheumatology2578-57452023-09-015947448010.1002/acr2.11599Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid ArthritisYogan Kisten0Laurent Arnaud1Adrian Levitsky2Noémi Györi3Per Larsson4Aase Hensvold5Anca Catrina6Erik af Klint7Hamed Rezaei8Karolinska Institute and Karolinska University Hospital Stockholm SwedenHôpitaux Universitaires de Strasbourg Service de Rhumatologie National Reference Center for Rare Systemic Autoimmune Diseases Strasbourg Alsace‐Champagne‐Ardenne FranceKarolinska Institute and Karolinska University Hospital Stockholm SwedenKarolinska Institute and Karolinska University Hospital Stockholm SwedenAcademic Specialist Center Stockholm SwedenKarolinska Institute and Karolinska University Hospital and Academic Specialist Center Stockholm SwedenKarolinska Institute and Karolinska University Hospital and Academic Specialist Center Stockholm SwedenKarolinska Institute and Karolinska University Hospital Stockholm SwedenKarolinska Institute and Karolinska University Hospital Stockholm SwedenObjective 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.https://doi.org/10.1002/acr2.11599
spellingShingle Yogan Kisten
Laurent Arnaud
Adrian Levitsky
Noémi Györi
Per Larsson
Aase Hensvold
Anca Catrina
Erik af Klint
Hamed Rezaei
Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid Arthritis
ACR Open Rheumatology
title Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid Arthritis
title_full Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid Arthritis
title_fullStr Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid Arthritis
title_full_unstemmed Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid Arthritis
title_short Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid Arthritis
title_sort distinct fluorescence optical imaging patient clusters emerge for seropositive and seronegative rheumatoid arthritis
url https://doi.org/10.1002/acr2.11599
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