IDH-mutant myeloid neoplasms are associated with seronegative rheumatoid arthritis and innate immune activation

Lih En Hong; Mihir D Wechalekar; Monika Kutyna; Annabelle Small; Kelly Lim; Chloe Thompson-Peach; Joule J Li; Rakchha Chhetri; Hamish S Scott; Anna Brown; Christopher N Hahn; David T Yeung; Salvia Sajid; Nirmal Robinson; Ranjeny Thomas; Susan Branford; Richard J D'Andrea; Saumya E Samaraweera; Mrinal Patnaik; Susanna Proudman; Daniel Thomas; Chung Hoow Kok; Mithun V Shah; Devendra K Hiwase

doi:10.1182/blood.2023023593

IDH-mutant myeloid neoplasms are associated with seronegative rheumatoid arthritis and innate immune activation

Blood. 2024 May 2;143(18):1873-1877. doi: 10.1182/blood.2023023593.

Authors

Lih En Hong^{1

2}, Mihir D Wechalekar^{1

3

4}, Monika Kutyna^{5

6}, Annabelle Small⁴, Kelly Lim^{2

6}, Chloe Thompson-Peach^{2

6}, Joule J Li⁵, Rakchha Chhetri^{2

5}, Hamish S Scott^{2

7

8}, Anna Brown^{2

7

8}, Christopher N Hahn^{2

7

8}, David T Yeung^{2

5

6}, Salvia Sajid⁹, Nirmal Robinson⁷, Ranjeny Thomas¹⁰, Susan Branford^{2

7

8}, Richard J D'Andrea⁷, Saumya E Samaraweera⁷, Mrinal Patnaik¹¹, Susanna Proudman^{1

2}, Daniel Thomas^{2

5

6}, Chung Hoow Kok^{2

6

7}, Mithun V Shah¹¹, Devendra K Hiwase^{2

5

6}

Affiliations

¹ Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia.
² Adelaide Medical School, University of Adelaide, Adelaide, Australia.
³ Rheumatology Unit, Flinders Medical Centre, Adelaide, Australia.
⁴ College of Medicine and Public Health, Flinders University, Adelaide, Australia.
⁵ Haematology Department, Central Adelaide Local Health Network, Adelaide, Australia.
⁶ Blood Cancer, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia.
⁷ Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia.
⁸ Genetics and Molecular Pathology, SA Pathology, Adelaide, Australia.
⁹ Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Frazer Institute, University of Queensland, Brisbane, Australia.
¹¹ Division of Hematology, Mayo Clinic, Rochester, MN.

PMID: 38457663
PMCID: PMC11076852 (available on 2025-05-02)
DOI: 10.1182/blood.2023023593

Abstract

High prevalence of IDH mutations in seronegative rheumatoid arthritis (RA) with myeloid neoplasm, elevated 2-hydroxyglutarate, dysregulated innate immunity, and proinflammatory microenvironment suggests causative association between IDH mutations and seronegative RA. Our findings merit investigation of IDH inhibitors as therapeutics for seronegative IDH-mutated RA.

© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Aged
Arthritis, Rheumatoid* / genetics
Arthritis, Rheumatoid* / immunology
Female
Humans
Immunity, Innate*
Isocitrate Dehydrogenase* / genetics
Male
Middle Aged
Mutation*

Substances

Isocitrate Dehydrogenase
IDH1 protein, human