Peripheral blood UBA1 variant burden predicts poor outcomes in VEXAS syndrome: a nationwide prospective study

Kirino, Y; Maeda, A; Higashitani, K; Horita, N; Asano, T; Migita, K; Motomura, Y; Rokutanda, R; Kobayashi, D; Tamura, M; Kanazawa, N; Furuhashi, K; Kondo, Y; Nagahata, K; Takahashi, H; Kobayashi, H; Yao, S; Yamagami, K; Uchino, K; Hidaka, Y; Ida, H; Kishida, D; Sato, T; Ichinose, K; Miyamae, T; Tsujimoto, K; Inoue, Y; Fujieda, Y; Mishima, K; Tsuji, T; Tanaka, K; Noda, H; Isogai, S; Miyoshi, Y; Yokogawa, N; Ota, S; Sakuraba, H; Nishi, J; Inoue, T; Muraoka, S; Nanki, T; Shimizu, T; Koga, T; Inaba, Y; Matsubara, M; Yoshimoto, K; Hasegawa, A; Ikeda, K; Motohashi, R; Takeuchi, Y; Shiratsuchi, M; Moriyama, M; Noda, K; Saito, S; Hagiyama, H; Honda, T; Kageyama, R; Nakatani, N; Goto, T; Kishimoto, M; Watanabe, T; Yamaguchi, Y; Nishikomori, R; Ohara, O; Ban, T; Tamura, T; Nakajima, H

doi:10.1016/j.ard.2026.03.003

Autoinflammatory & rare systemic diseases

Peripheral blood UBA1 variant burden predicts poor outcomes in VEXAS syndrome: a nationwide prospective study

Ann Rheum DisPublished 1 Apr 2026Prospective cohort study

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Authors' conclusion

Baseline pathogenic UBA1 VAF serves as a potent prognostic biomarker for poor outcomes in VS

Study context

Population: Suspected VEXAS syndrome cases screened by next-generation sequencing for pathogenic UBA1 variants, nationwide registry in Japan34 independent validation patients
Participants: 60 vs 45

Exposure: Patients with pathogenic UBA1 variants (VEXAS) vs male patients with VS-like syndrome without UBA1 variants
VEXASn = 60
VS-liken = 45reference
Outcome: Poor prognosis, defined as death or transfusion dependence; predictors including baseline VAF
Follow-up: 1 year

Methodological detailsnationwide prospective registry, multivariable Cox regression, independent validation cohort

Nationwide prospective registry
Multivariable Cox regression
Independent validation cohort

Main finding

As reported in the abstract

Predictors of poor prognosis (death or transfusion dependence), multivariable Cox regression

Higher baseline variant allele frequency (VAF) independently predicted poor prognosis
Higher prednisolone (PSL) dose independently predicted poor prognosis
Association of higher VAF with poor outcomes confirmed in 34 independent patients with VS

Observational data: associations, not effects.

Further findings

Disease activity (VEXASCAF), C-reactive protein (CRP) and PSL dose over follow-up · median follow-up of 343 days

VEXASCAF and CRP levels decreased; PSL dose did not significantly change

Survival by UBA1 p.Met41Leu variant

p.Met41Leu carriers showed better survival after adjusting for disease onset

Prognosis in VEXAS-like patients

Similarly poor prognosis in VEXAS-like patients

Safety

Grade ≥3 adverse events (AEs) occurred in 50% of patients within 1 year

Reference

Authors: Kirino Y, Maeda A, Higashitani K, Horita N, Asano T, Migita K, et al.
All 67 authors
Kirino Y, Maeda A, Higashitani K, Horita N, Asano T, Migita K, Motomura Y, Rokutanda R, Kobayashi D, Tamura M, Kanazawa N, Furuhashi K, Kondo Y, Nagahata K, Takahashi H, Kobayashi H, Yao S, Yamagami K, Uchino K, Hidaka Y, Ida H, Kishida D, Sato T, Ichinose K, Miyamae T, Tsujimoto K, Inoue Y, Fujieda Y, Mishima K, Tsuji T, Tanaka K, Noda H, Isogai S, Miyoshi Y, Yokogawa N, Ota S, Sakuraba H, Nishi J, Inoue T, Muraoka S, Nanki T, Shimizu T, Koga T, Inaba Y, Matsubara M, Yoshimoto K, Hasegawa A, Ikeda K, Motohashi R, Takeuchi Y, Shiratsuchi M, Moriyama M, Noda K, Saito S, Hagiyama H, Honda T, Kageyama R, Nakatani N, Goto T, Kishimoto M, Watanabe T, Yamaguchi Y, Nishikomori R, Ohara O, Ban T, Tamura T, Nakajima H
Journal: Annals of the Rheumatic Diseases
Published: 1 Apr 2026
DOI: 10.1016/j.ard.2026.03.003
PubMed: 41927375

Topic: Autoinflammatory & rare systemic diseases

Exposure definitions

VEXAS: patients with pathogenic UBA1 variants (all males; median age, 74 years)
VS-like: male patients with VS-like syndrome of similar age but without UBA1 variants

Original publication

Peripheral blood UBA1 variant burden predicts poor outcomes in VEXAS syndrome: a nationwide prospective study. Ann Rheum Dis. Published 1 April 2026. doi:10.1016/j.ard.2026.03.003

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