Jónasdóttir Ásta Dögg, Hemmingsson Peter, Schwarz Angelina, Söderberg Magnus, Wernerson Annika, Qureshi Abdul Rashid, Antovic Aleksandra, Gunnarsson Iva, Bruchfeld Annette
Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden.
Division of Nephrology, Department of Medicine, Landspitali - The National University Hospital, Reykjavik, Iceland.
Clin Kidney J. 2025 Apr 18;18(5):sfaf086. doi: 10.1093/ckj/sfaf086. eCollection 2025 May.
The aim of the study was to investigate urinary and serum tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as potential biomarkers in a longitudinal cohort of patients with ANCA-associated vasculitis (AAV).
Patients with active AAV were included in the study. The Birmingham Vasculitis Score 2003 (BVAS) was used for assessment of disease activity and C-reactive protein (CRP), creatinine, albuminuria, and serum (s) and urinary (u) TWEAK levels were measured at baseline and 6-month follow-up. sTWEAK was measured in population-based controls for comparison. Kidney biopsies from AAV patients were stained for TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14) using immunohistochemistry (IHC).
sTWEAK was measured in 74 patients and uTWEAK in 69 patients, 42 of whom had kidney involvement. uTWEAK-to-creatinine ratio (uTWEAK/Cr) was significantly higher at baseline compared with follow-up (median 7.21 vs 4.94 ng/mmol, < .0001). Patients with kidney involvement had higher uTWEAK/Cr levels compared with those without ( = .03). A correlation was found between uTWEAK/Cr and BVAS ( = .006), albuminuria ( = .022) and crescentic changes ( = .03). sTWEAK levels were higher in patients at inclusion than at follow-up ( = .009) but no difference was found when comparing patients and controls, nor did sTWEAK correlate with BVAS. IHC staining showed a clear expression of TWEAK but a fainter pattern of Fn14 in kidney biopsies from AAV patients.
uTWEAK/Cr correlated with BVAS, albuminuria and number of crescents in active AAV and may be a useful biomarker in assessing disease activity in patients with AAV, whereas sTWEAK level is not.
本研究旨在调查尿和血清肿瘤坏死因子(TNF)样凋亡弱诱导剂(TWEAK)作为抗中性粒细胞胞浆抗体相关性血管炎(AAV)纵向队列中的潜在生物标志物。
纳入活动性AAV患者。采用2003年伯明翰血管炎评分(BVAS)评估疾病活动度,并在基线和6个月随访时测量C反应蛋白(CRP)、肌酐、蛋白尿以及血清(s)和尿(u)TWEAK水平。在基于人群的对照中测量sTWEAK以作比较。使用免疫组织化学(IHC)对AAV患者的肾活检组织进行TWEAK及其受体成纤维细胞生长因子诱导14(Fn14)染色。
74例患者测量了sTWEAK,69例患者测量了uTWEAK,其中42例有肾脏受累。与随访时相比,基线时uTWEAK与肌酐比值(uTWEAK/Cr)显著更高(中位数7.21对4.94 ng/mmol,P<0.0001)。有肾脏受累的患者uTWEAK/Cr水平高于无肾脏受累者(P=0.03)。发现uTWEAK/Cr与BVAS(P=0.006)、蛋白尿(P=0.022)和新月体改变(P=0.03)之间存在相关性。纳入时患者的sTWEAK水平高于随访时(P=0.009),但在比较患者和对照时未发现差异,sTWEAK也与BVAS无相关性。免疫组织化学染色显示AAV患者肾活检组织中TWEAK表达清晰,但Fn14染色较淡。
在活动性AAV中,uTWEAK/Cr与BVAS、蛋白尿和新月体数量相关,可能是评估AAV患者疾病活动度的有用生物标志物,而sTWEAK水平则不然。