A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Clonal hematopoiesis is associated with distinct rheumatoid arthritis phenotypes
Tekijät: 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
Kustantaja: American Association for the Advancement of Science (AAAS)
Kustannuspaikka: WASHINGTON
Julkaisuvuosi: 2025
Journal: Science Advances
Tietokannassa oleva lehden nimi: Science Advances
Lehden akronyymi: SCI ADV
Artikkelin numero: eadt9846
Vuosikerta: 11
Numero: 18
Sivujen määrä: 14
ISSN: 2375-2548
eISSN: 2375-2548
DOI: https://doi.org/10.1126/sciadv.adt9846
Verkko-osoite: https://doi.org/10.1126/sciadv.adt9846
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/498471895
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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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.).
