Tsouris Zisis, Liaskos Christos, Dardiotis Efthymios, Scheper Thomas, Tsimourtou Vana, Meyer Wolfgang, Hadjigeorgiou George, Bogdanos Dimitrios P
1Department of Neurology, University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
2Department of Rheumatology and Clinical Immunology, University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa 40500 Greece.
Auto Immun Highlights. 2020 Apr 10;11(1):7. doi: 10.1186/s13317-020-00130-4. eCollection 2020 Dec.
Abnormal liver function tests are frequently seen in patients with multiple sclerosis (MS) and their origin at times is attributed to the possible co-occurrence or the de novo induction of autoimmune liver diseases (AILD), namely autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but comprehensive analysis of AILD-related autoantibody has not been carried out.
To assess the presence of AILD-related autoantibodies in a well-defined cohort of MS patients, and to assess their clinical significance.
133 MS (93 female) patients (102 RRMS, 27 SPMS, and 5 PPMS), mean age 42.7 ± 11.9 SD years, mean duration of disease 11.2 ± 7.2 years were studied. 150 age and sex-matched healthy individuals were tested as normal controls (NCs).Autoantibody testing was performed by indirect immunofluorescence (IF) using triple tissue and HEp-2, a multiparametric line immunoassay detecting anti-LKM1(anti-CYP2D6), anti-LC1(anti-FTCD), soluble liver antigen/liver-pancreas(anti-SLA/LP), AMA-M2, and AMA-MIT3 (BPO), PBC-specific ANA (anti-gp210, anti-sp100 and anti-PML), and ELISA for anti-F-actin SMA and anti-dsDNA antibodies.
Reactivity to at least one autoantibody was more frequent in MS patients compared to NCs (30/133, 22.6% vs 12/150, 8%) NCs (p = 0.00058). SMAs by IIF were more frequent in MS patients (18/133, 13.53%) compared to NCs (6/150, 4%, p = 0.002%). The AIH-1 related anti-F-actin SMA by ELISA were present in 21 (15.8%), at relatively low titres (all but three of the SMA-VG pattern by IF); anti-dsDNA in 3 (2.3%), and anti-SLA/LP in none; AIH-2 anti-LKM1 autoantibodies in 1 (0.8%, negative by IF), and anti-LC1 in none; PBC-specific AMA-M2 in 2 (1.5%, both negative for AMA-MIT3 and AMA by IF) and PBC-specific ANA anti-PML in 6 (4.5%), anti-sp100 in 1 (0.8%) and anti-gp210 in 1 (0.8%). Amongst the 30 MS patients with at least one autoantibody positivity, only 4 (3%) had overt AILD (2 AIH-1 and 2 PBC). Autoantibody positivity did not differ between naïve MS patients and patients under treatment.
Despite the relatively frequent presence of liver autoantibodies, tested either by IF or molecular assays, overt AILD is rather infrequent discouraging autoantibody screening strategies of MS patients in the absence of clinical suspicion.
肝功能检查异常在多发性硬化症（MS）患者中较为常见，其病因有时被归因于自身免疫性肝病（AILD）可能的合并发生或新发，即自身免疫性肝炎（AIH）和原发性胆汁性胆管炎（PBC），但尚未对与AILD相关的自身抗体进行全面分析。
评估明确队列的MS患者中与AILD相关的自身抗体的存在情况，并评估其临床意义。
研究了133例MS患者（93例女性）（102例复发缓解型MS、27例继发进展型MS和5例原发进展型MS），平均年龄42.7±11.9标准差岁，平均病程11.2±7.2年。150名年龄和性别匹配的健康个体作为正常对照（NCs）进行检测。采用间接免疫荧光法（IF），使用三联组织和人喉癌上皮细胞（HEp-2）进行自身抗体检测，采用多参数线性免疫分析法检测抗LKM1（抗CYP2D6）、抗LC1（抗FTCD）、可溶性肝抗原/肝胰抗原（抗SLA/LP）、AMA-M2和AMA-MIT3（BPO）、PBC特异性抗核抗体（抗gp210、抗sp100和抗PML），并采用酶联免疫吸附测定法检测抗F-肌动蛋白平滑肌肌动蛋白（SMA）和抗双链DNA抗体。
与NCs相比，MS患者中对至少一种自身抗体呈反应性的情况更为常见（30/133，22.6%对12/150，8%）（p = 0.00058）。与NCs相比，MS患者中通过IIF检测到的SMA更为常见（18/133，13.53%对（6/150，4%，p = 0.002%）。通过酶联免疫吸附测定法检测到的与AIH-1相关的抗F-肌动蛋白SMA存在于21例（15.8%）患者中，滴度相对较低（除3例IF检测为SMA-VG模式外）；抗双链DNA存在于3例（2.3%）患者中，抗SLA/LP无阳性；AIH-2抗LKM1自身抗体存在于1例（0.8%，IF检测为阴性），抗LC1无阳性；PBC特异性AMA-M2存在于2例（1.5%，IF检测AMA-MIT3和AMA均为阴性），PBC特异性抗核抗体抗PML存在于6例（4.5%），抗sp100存在于1例（0.8%），抗gp210存在于1例（0.8%）。在30例至少有一种自身抗体阳性的MS患者中，只有4例（3%）患有明显的AILD（2例AIH-1和2例PBC）。初发MS患者和接受治疗的患者之间自身抗体阳性情况无差异。
尽管通过IF或分子检测方法检测到肝脏自身抗体相对较为常见，但明显的AILD相当少见，这使得在没有临床怀疑的情况下对MS患者进行自身抗体筛查策略并不乐观。
