Wilde Anne-Christin Beatrice, Greverath Lena Maria, Steinhagen Lara Marleen, de Chamorro Nina Wald, Leicht Elise, Fischer Janett, Herta Toni, Berg Thomas, Preuss Beate, Klein Reinhild, Tacke Frank, Müller Tobias
Department of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, Germany.
J Clin Med. 2022 Jan 28;11(3):681. doi: 10.3390/jcm11030681.
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) constitute rare chronic inflammatory biliary diseases which likely comprise genetic, environmental and autoimmune factors. Specific inhibitory (auto-) antibodies against the muscarinic acetylcholine receptor type 3 (mAChR3 auto-ab) may contribute to the pathogenesis of chronic biliary inflammation by modulating mAChR3- mediated signaling.
The aim of this study was to analyze the prevalence and relevance of inhibitory mAChR3 auto-ab (mAChR3inh+ auto-ab) in a large cohort of PBC patients from two independent tertiary centers in Berlin and Leipzig in comparison to a large PSC cohort. Baseline parameters and response rates to standard treatment with ursodeoxycholic acid (UDCA) were characterized with respect to the individual mAChR3 auto-ab status.
In total, the study population comprised 437 PBC patients, 187 PSC patients and 80 healthy controls. Clinical and laboratory baseline characteristics were retrieved from medical records. The response to ursodeoxycholic acid (UDCA) therapy after 12 months of treatment was available in 176 PBC and 45 PSC patients.
The prevalence of mAChR3inh+ auto-ab was significantly higher among PBC patients (11.2%, 49/437; = 0.008 vs. healthy controls) and PSC patients (33.6%, 63/187; < 0.0001 vs. healthy controls) compared to healthy controls (2.5%, 2/80), respectively. PBC patients with mAChR3inh+ auto-ab exhibited significantly higher levels of alkaline phosphatase (ALP) and bilirubin, which constitute established parameters for PBC risk stratification. Moreover, mAChR3inh+ PBC patients tended to show decreased response rates to UDCA therapy compared to PBC patients without mAChR3inh+ auto-ab (mAChR3- PBC). In contrast, PSC patients with mAChR3inh+ auto-ab showed no significant differences in laboratory findings compared to mAChR3 auto-ab negative (mAChR3-) PSC patients.
MAChR3inh+ auto-ab might be involved in the pathogenesis and treatment response of chronic biliary inflammation in patients with PBC but not in patients with PSC.
原发性胆汁性胆管炎（PBC）和原发性硬化性胆管炎（PSC）是罕见的慢性炎症性胆道疾病，可能由遗传、环境和自身免疫因素引起。针对毒蕈碱型乙酰胆碱受体3（mAChR3）的特异性抑制性（自身）抗体（mAChR3自身抗体）可能通过调节mAChR3介导的信号传导，参与慢性胆道炎症的发病机制。
本研究旨在分析柏林和莱比锡两个独立三级中心的一大群PBC患者中抑制性mAChR3自身抗体（mAChR3inh+自身抗体）的患病率及其相关性，并与一大群PSC患者进行比较。根据个体的mAChR3自身抗体状态，对基线参数和熊去氧胆酸（UDCA）标准治疗的反应率进行特征分析。
研究人群共包括437例PBC患者、187例PSC患者和80例健康对照。从病历中获取临床和实验室基线特征。176例PBC患者和45例PSC患者有治疗12个月后对熊去氧胆酸（UDCA）治疗的反应情况。
与健康对照（2.5%，2/80）相比，PBC患者（11.2%，49/437；P = 0.008）和PSC患者（33.6%，63/187；P < 0.0001）中mAChR3inh+自身抗体的患病率显著更高。有mAChR3inh+自身抗体的PBC患者碱性磷酸酶（ALP）和胆红素水平显著更高，这是PBC风险分层的既定参数。此外，与无mAChR3inh+自身抗体（mAChR3- PBC）的PBC患者相比，有mAChR3inh+自身抗体的PBC患者对UDCA治疗的反应率往往较低。相比之下，有mAChR3inh+自身抗体的PSC患者与mAChR3自身抗体阴性（mAChR3-）的PSC患者相比，实验室检查结果无显著差异。
mAChR3inh+自身抗体可能参与PBC患者慢性胆道炎症的发病机制和治疗反应，但不参与PSC患者的发病机制和治疗反应。
