Landscape of Somatic Mutations in a Large Cohort of Chinese Patients With Immune Dysregulations

Fu, J; Fu, Q; Wang, J; Wang, Q; Zhang, L; Chi, H; Zhang, L; Sun, L; Huang, Y; He, T; Yao, Y; Han, X; Ma, S; Liu, C; Liu, L; Chen, X; Wang, S; Jiang, H; Zheng, W; Zheng, S; Ye, Q; Du, Y; Guo, L; Zhu, J; Li, G; Zhang, C; Lin, Z; Ju, X; Han, Y; Chen, W; Lin, J; Xue, J; Cheng, H; Xu, C; Huang, L; Qin, L; Zeng, J; Mei, Y; Yan, T; Lv, Q; Shangguan, Y; Zheng, C; He, X; Liu, H; Chen, X; Xie, H; Li, X; Jin, Y; Peng, J; Lin, B; Huang, Y; Wang, X; Yang, X; Jiang, N; Wang, W; Wu, T; Wu, D; Zhu, Y; Fu, Y; Chen, J; Wang, R; Liu, X; Jiang, D; Xiao, H; Su, B; Zhang, B; Wu, F; Hu, Q; Yang, C; Lu, M; Ye, S; Shen, M; Song, H; Chen, J; Yang, J; Liu, Z; Yu, X; Zhou, Q

doi:10.1002/art.70126

Autoinflammatory & rare systemic diseases

Landscape of Somatic Mutations in a Large Cohort of Chinese Patients With Immune Dysregulations

Arthritis RheumatolPublished 14 Apr 2026Cross-sectional study

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Authors' conclusion

This study delineated the genetic landscape of pathogenic somatic mutations underlying autoinflammatory and autoimmune diseases, offering valuable insights for genetic diagnosis and targeted therapies.

Study context

Population: Patients with autoinflammatory or autoimmune diseases previously negative for germline mutations on whole-exome sequencing, 41 medical centres across China
Participants: 2,912 patients41 centres

Exposure: Adults vs Children
Outcome: Pathogenic somatic mutations in 185 immune-related genes

Methodological detailsmulticentre, targeted panel of 185 immune-related genes, germline-negative by whole-exome sequencing

Multicentre
Targeted panel of 185 immune-related genes
Germline-negative by whole-exome sequencing

Main finding

As reported in the abstract

Pathogenic somatic mutation detection rate

Adults1.35%

Children0.97%

Observational data: associations, not effects.

Further findings

Somatic mutations in Ras-related genes

Patients with Ras-related somatic mutations: 7

Clonal hematopoiesis-associated mutations (adults)

Mutations: 39
Adult patients: 36

Dynamics of mutated myeloid cells

Myeloid cells harboring somatic mutations expanded during flare and reduced during remission
Disregarding dynamic rise of variant allele fraction during progression led to therapeutic failure

Reference

Authors: Fu J, Fu Q, Wang J, Wang Q, Zhang L, Chi H, et al.
All 78 authors
Fu J, Fu Q, Wang J, Wang Q, Zhang L, Chi H, Zhang L, Sun L, Huang Y, He T, Yao Y, Han X, Ma S, Liu C, Liu L, Chen X, Wang S, Jiang H, Zheng W, Zheng S, Ye Q, Du Y, Guo L, Zhu J, Li G, Zhang C, Lin Z, Ju X, Han Y, Chen W, Lin J, Xue J, Cheng H, Xu C, Huang L, Qin L, Zeng J, Mei Y, Yan T, Lv Q, Shangguan Y, Zheng C, He X, Liu H, Chen X, Xie H, Li X, Jin Y, Peng J, Lin B, Huang Y, Wang X, Yang X, Jiang N, Wang W, Wu T, Wu D, Zhu Y, Fu Y, Chen J, Wang R, Liu X, Jiang D, Xiao H, Su B, Zhang B, Wu F, Hu Q, Yang C, Lu M, Ye S, Shen M, Song H, Chen J, Yang J, Liu Z, Yu X, Zhou Q
Journal: Arthritis & Rheumatology
Published: 14 Apr 2026
DOI: 10.1002/art.70126
PubMed: 41801095

Topic: Autoinflammatory & rare systemic diseases

Key notes

Previously reported and novel somatic mutations identified in genes such as UBA1, KRAS and NLRP3
Pathogenic somatic TNFAIP3 mutations discovered first in autoinflammatory diseases

Original publication

Landscape of Somatic Mutations in a Large Cohort of Chinese Patients With Immune Dysregulations. Arthritis Rheumatol. Published 14 April 2026. doi:10.1002/art.70126

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