Meinel Katharina, Szabo Doloresz, Dezsofi Antal, Pohl Sina, Strini Tanja, Greimel Theresa, Aguiriano-Moser Victor, Haidl Harald, Wagner Martin, Schlagenhauf Axel, Jahnel Jörg
Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Front Pediatr. 2022 May 11;10:903360. doi: 10.3389/fped.2022.903360. eCollection 2022.
The exact etiology of pruritus in chronic cholestasis is unknown. Pruritus intensity does not correlate with common biochemical indices and there is a lack of biomarkers guiding diagnosis and treatment. We explored profiles of bile acids (BA) and muricholic acids (MCA) as well as autotaxin (ATX) antigen levels as potential circulating biomarkers of pruritus in pediatric patients.
In 27 pediatric cholestatic patients [autoimmune sclerosing cholangitis (ASC) = 20 (with pruritus = 6, without pruritus = 14); progressive familial intrahepatic cholestasis (PFIC) = 7 (with pruritus = 5, without pruritus = 2)] and 23 age-matched controls pruritus was assessed by a visual analog scale of pruritus (PVAS). We obtained profiles of serum human BA including MCA using a mass-spectrometry assay and ATX antigen levels with a commercial ELISA.
PFIC and ASC patients exhibited significantly higher BA-, and MCA levels, than healthy controls, but only PFIC patients showed elevated ATX antigen levels higher [median: 1,650 ng/ml, interquartile rang (IQR): 776.9-3,742] compared to controls (median: 315.9 ng/ml, IQR: 251.1-417.2; PFIC = 0.0003). ASC patients with pruritus showed only a minor increase in total BA (tBA) levels (median: 76.5 μmol/L, IQR: 54.7-205), but strikingly higher T-conjugated BA (median: 16.4 μmol/L, IQR: 8.9-41.4) and total MCA (tMCA) (median: 1.15 μmol/L, IQR: 0.77-2.44) levels compared to ASC patients without pruritus (tBA median: 24.3 μmol/L, IQR: 16.2-80.8; < 0.0408; T-conjugated BA median: 1.3 μmol/L, IQR: 0.8-4.9; = 0.0023; tMCA median: 0.30 μmol/L, IQR: 0.13-0.64, = 0.0033). BA/MCA profiles distinctly differed depending on presence/absence of pruritus. Different from PFIC patients, ATX antigen levels were not significantly elevated in ASC patients with (median: 665.8 ng/ml, IQR: 357.8-1,203) and without pruritus (median: 391.0 ng/ml, IQR: 283.2-485.6). In ASC patients, tBA, tMCA, and ATX antigen levels did not correlate with pruritus severity.
Despite the same underlying disease, pediatric ASC patients with pruritus exhibit significantly altered BA profiles and MCA levels compared to ASC patients without pruritus. ATX antigen levels seem to have little diagnostic or prognostic meaning in ASC patients. An increased ATX activity alone seems not to be causal for pruritus genesis in ASC patients.
[www.drks.de], identifier [DRKS00026913].
慢性胆汁淤积症瘙痒的确切病因尚不清楚。瘙痒强度与常见生化指标无关，且缺乏指导诊断和治疗的生物标志物。我们探讨了胆汁酸（BA）和鼠胆酸（MCA）的谱以及自分泌运动因子（ATX）抗原水平，作为儿科患者瘙痒的潜在循环生物标志物。
在27例儿科胆汁淤积症患者中[自身免疫性硬化性胆管炎（ASC）=20例（有瘙痒=6例，无瘙痒=14例）；进行性家族性肝内胆汁淤积症（PFIC）=7例（有瘙痒=5例，无瘙痒=2例）]，并在23例年龄匹配的对照者中，通过瘙痒视觉模拟量表（PVAS）评估瘙痒情况。我们使用质谱分析法获得血清人BA（包括MCA）的谱，并使用商业酶联免疫吸附测定法测定ATX抗原水平。
PFIC和ASC患者的BA和MCA水平显著高于健康对照者，但只有PFIC患者的ATX抗原水平升高[中位数：1650 ng/ml，四分位间距（IQR）：776.9 - 3742]，而对照者的中位数为315.9 ng/ml，IQR：251.1 - 417.2；PFIC，P = 0.0003）。有瘙痒的ASC患者总BA（tBA）水平仅略有升高（中位数：76.5 μmol/L，IQR：54.7 - 205），但与无瘙痒的ASC患者相比，T - 结合BA（中位数：16.4 μmol/L，IQR：8.9 - 41.4）和总MCA（tMCA）（中位数：1.15 μmol/L，IQR：0.77 - 2.44）水平显著更高（tBA中位数：24.3 μmol/L，IQR：16.2 - 80.8；P < 0.0408；T - 结合BA中位数：1.3 μmol/L，IQR：0.8 - 4.9；P = 0.0023；tMCA中位数：0.30 μmol/L，IQR：0.13 - 0.64，P = 0.0033）。BA/MCA谱根据有无瘙痒明显不同。与PFIC患者不同，有瘙痒（中位数：665.8 ng/ml，IQR：357.8 - 1203）和无瘙痒（中位数：391.0 ng/ml，IQR：283.
