Clonal hematopoiesis is associated with distinct rheumatoid arthritis phenotypes - UTU Research Portal

A1 Refereed original research article in a scientific journal

Clonal hematopoiesis is associated with distinct rheumatoid arthritis phenotypes

Authors: Hiitol,a Emil; Korhonen, Juuso; Kokkonen, Heidi; Koskela, Jukka; Kankainen, Matti; Alakuijala, Milla; Liu, Aoxing; Lundgren, Sofie; Häppölä, Paavo; Almusa, Henrikki; Ellonen, Pekka; Savola, Paula; Kelkka, Tiina; Leirisalo-Repo, Marjatta; Koivuniemi, Riitta; Peltomaa, Ritva; Pirilä, Laura; Isomäki, Pia; Kauppi, Markku; Kaipiainen-Seppänen, Oili; Starskaia, Inna; Virtanen, Anniina T.; Lahesmaa, Riitta; Silvennoinen, Olli; Genovese, Giulio; Ganna, Andrea; Rantapää-Dahlqvist, Solbritt; Mustjoki, Satu; Myllymäki, Mikko

Publisher: American Association for the Advancement of Science (AAAS)

Publishing place: WASHINGTON

Publication year: 2025

Journal: Science Advances

Journal name in source: Science Advances

Journal acronym: SCI ADV

Article number: eadt9846

Volume: 11

Issue: 18

Number of pages: 14

ISSN: 2375-2548

eISSN: 2375-2548

DOI: https://doi.org/10.1126/sciadv.adt9846(external)

Web address : https://doi.org/10.1126/sciadv.adt9846(external)

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/498471895(external)

Abstract

Clonal hematopoiesis (CH) becomes more prevalent with aging and may influence inflammatory diseases by altering immune function. While CH of indeterminate potential (CHIP) promotes inflammation in nonmalignant conditions, its relationship with rheumatoid arthritis (RA) remains unknown. We analyzed CHIP mutations in RA using two population-level cohorts and patients with newly diagnosed RA. CHIP was associated with prevalent RA in 10,089 FINRISK study participants with whole-exome sequencing (OR, 2.06; P = 0.029) and in the FinnGen cohort (n = 520,210; OR, 1.49; P < 0.001) using single-nucleotide polymorphism array-based CHIP annotation. In FinnGen, CHIP was also associated with inferior overall survival in participants with RA (P = 0.013). In newly diagnosed RA (n = 573), DNMT3A-mutated seropositive patients had increased inflammatory markers and disease activity compared with patients without CHIP. In contrast, TET2 mutations were enriched in seronegative RA (P = 0.009). Our findings provide further evidence for the context-dependent association between CHIP and inflammation, with potential therapeutic implications.

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Funding information in the publication:
This work was supported by the Sigrid Juselius Foundation (M.M., S.M., and O.S.), European Research Council (S.M.), Research Council of Finland (M.M., S.M., O.S., and J.Kos.), Finnish Medical Foundation (M.M.), Finnish Cultural Foundation (M.M.), Signe and Ane Gyllenberg Foundation (S.M.), Helsinki Institute for Life Science Fellow Funding (S.M.), Cancer Foundation Finland (O.S.), Tampere Tuberculosis Foundation (O.S.), and Competitive Research Funding of the Tampere University Hospital (O.S.).