Annals of the rheumatic diseases · 2025
AYLo study-elevated relapse risk and dysregulated proinflammatory signalling in giant cell arteritis patients with mosaic loss of the Y chromosome.
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Petzinna Simon M, Kirch Sophie-Marie, Adamson Maike S, Xi De, Bauer Claus-Jürgen, Kreis Lena, Gheitasi Reza, Karakostas Pantelis, Behrendt Rayk, Nickenig Georg, Zimmer Sebastian, Jamin Raul N, Schäfer Valentin S
Аннотация
OBJECTIVES: To assess the prevalence of mosaic loss of the Y chromosome (mLOY) in giant cell arteritis (GCA) and its impact on disease activity.
METHODS: Patients diagnosed with GCA were prospectively recruited, and their leukocyte mLOY burden was analysed. The optimal mLOY threshold for predicting relapse was determined using the receiver operating characteristic curve and Youden index. Relapse-free survival was assessed using Kaplan-Meier analysis with the log-rank test. Levels of selected proinflammatory cytokines were quantified using a multiplex array.
RESULTS: A total of 74 GCA patients were enrolled (mean, 76.0 years; SD, 10.7). At inclusion, 25.7% (19/74) of patients exhibited active disease. Relapses occurred in 23.0% of patients. The median mLOY burden was 17.8% (SD, 23.7%). An optimal threshold of 10.2% was identified for predicting relapse. Patients exceeding this cutoff had a significantly higher relapse risk (P < .001) with a shorter relapse-free survival (647 vs 992 days; P < .001). Multivariable Cox regression confirmed mLOY >10.2% as an independent predictor of relapse (hazard ratio, 17.4; 95% CI, 3.5-86.0; P = .003). In multiplex analysis, mLOY was positively associated with interleukin (IL)-6 (P = .045; r = 0.24) across the cohort, with elevated IL-6 levels in remission patients with mLOY >10.2% (P = .010). In patients undergoing IL-6 receptor inhibitor treatment and in remission, mLOY was significantly positively associated with IL-6 (P = .002; r = 0.54) and IL-17A (P = .026; r = 0.40).
CONCLUSIONS: This study is the first to identify mLOY as a strong, independent predictor of relapse risk and to link mLOY with modulated proinflammatory signalling in GCA. Our findings suggest mLOY as a prognostic biomarker and underscore its possible role in the pathophysiology of GCA.
METHODS: Patients diagnosed with GCA were prospectively recruited, and their leukocyte mLOY burden was analysed. The optimal mLOY threshold for predicting relapse was determined using the receiver operating characteristic curve and Youden index. Relapse-free survival was assessed using Kaplan-Meier analysis with the log-rank test. Levels of selected proinflammatory cytokines were quantified using a multiplex array.
RESULTS: A total of 74 GCA patients were enrolled (mean, 76.0 years; SD, 10.7). At inclusion, 25.7% (19/74) of patients exhibited active disease. Relapses occurred in 23.0% of patients. The median mLOY burden was 17.8% (SD, 23.7%). An optimal threshold of 10.2% was identified for predicting relapse. Patients exceeding this cutoff had a significantly higher relapse risk (P < .001) with a shorter relapse-free survival (647 vs 992 days; P < .001). Multivariable Cox regression confirmed mLOY >10.2% as an independent predictor of relapse (hazard ratio, 17.4; 95% CI, 3.5-86.0; P = .003). In multiplex analysis, mLOY was positively associated with interleukin (IL)-6 (P = .045; r = 0.24) across the cohort, with elevated IL-6 levels in remission patients with mLOY >10.2% (P = .010). In patients undergoing IL-6 receptor inhibitor treatment and in remission, mLOY was significantly positively associated with IL-6 (P = .002; r = 0.54) and IL-17A (P = .026; r = 0.40).
CONCLUSIONS: This study is the first to identify mLOY as a strong, independent predictor of relapse risk and to link mLOY with modulated proinflammatory signalling in GCA. Our findings suggest mLOY as a prognostic biomarker and underscore its possible role in the pathophysiology of GCA.