Bayati Shaghayegh, Nazeer Jamsheela, Ng James, George Angel M, Hayes Michael, Little Mark A, Nilsson Peter, Pin Elisa
Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden.
ADAPT Centre, School of Computer Science and Statistics, Trinity College Dublin, Dublin, Ireland.
Rheumatology (Oxford). 2025 May 1;64(5):3142-3150. doi: 10.1093/rheumatology/keae540.
Identification of those at high and low risk of disease relapse is a major unmet need in the management of patients with ANCA-associated vasculitis (AAV). Precise stratification would allow tailoring of immunosuppressive medication. We profiled the autoantibody repertoire of AAV patients in remission to identify novel autoantibodies associated with relapse risk.
Plasma samples collected from 246 AAV patients in remission were screened for novel autoantibodies using in-house generated protein arrays including 42 000 protein fragments representing 18 000 unique human proteins. Patients were categorized based on the occurrence and frequency of relapses. We modelled the association between these antibodies and relapse occurrence using descriptive and high dimensional regression approaches.
We observed nine autoantibodies at higher frequency in samples from AAV patients experiencing multiple relapses compared with patients in long-term remission off therapy. LASSO analysis identified six autoantibodies that exhibited an association with relapse occurrence after sample collection. Antibodies targeting homeostatic iron regulator (HFE) and synaptotagmin 5 (SYT5) were identified as associated with relapse in both analyses.
Through a broad protein array-based autoantibody screening, we identified two novel autoantibodies directed against HFE and SYT5 as candidate biomarkers of relapse in AAV.
识别疾病复发风险高和低的患者是抗中性粒细胞胞浆抗体相关性血管炎（AAV）患者管理中一项尚未满足的主要需求。精确分层将有助于调整免疫抑制药物的使用。我们对缓解期AAV患者的自身抗体谱进行了分析，以识别与复发风险相关的新型自身抗体。
使用内部生成的蛋白质阵列对从246例缓解期AAV患者收集的血浆样本进行新型自身抗体筛查，该阵列包含代表18000种独特人类蛋白质的42000个蛋白质片段。根据复发的发生情况和频率对患者进行分类。我们使用描述性和高维回归方法对这些抗体与复发发生之间的关联进行建模。
我们观察到，与长期缓解且未接受治疗的患者相比，经历多次复发的AAV患者样本中九种自身抗体的出现频率更高。套索分析确定了六种在样本采集后与复发发生相关的自身抗体。在两项分析中，靶向稳态铁调节蛋白（HFE）和突触结合蛋白5（SYT5）的抗体均被确定与复发相关。
通过广泛的基于蛋白质阵列的自身抗体筛查，我们鉴定出两种针对HFE和SYT5的新型自身抗体，作为AAV复发的候选生物标志物。
