自身免疫性肝病中β-微管蛋白自身抗体与pANCA的关系及其临床意义。

IF 3.4 3区 医学 Q3 IMMUNOLOGY Clinical and experimental immunology Pub Date : 2024-04-23 DOI:10.1093/cei/uxad114
Beate Preuß, Amelie Frank, Birgit Terjung, Ulrich Spengler, Christoph Berg, Reinhild Klein
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引用次数: 0

摘要

有证据表明,pANCA(核周抗中性粒细胞细胞质抗体)在自身免疫性肝病中与人β-微管蛋白-5(TBB5)反应。在这里,我们重新评估了抗TBB5抗体的特异性和临床相关性。患有未经治疗的自身免疫性肝炎(AIH;n=53)、接受免疫抑制治疗的AIH(AIH-IS;n=125)、原发性硬化性胆管炎(PSC;n=40)、原发性胆汁性胆管管炎(PBC;n=250)、非自身免疫性肝病(n=158)、炎症性肠病(IBD;n=30),健康个体(n=62)通过酶联免疫吸附试验(ELISA)检测针对重组人TBB5的IgG和IgA抗体。免疫荧光法检测pANCA。血清用TBB5与溴化氰活化的琼脂糖偶联吸收。未经治疗的AIH患者IgG抗TBB5的患病率和反应性(68%;任意单位[AU]中位数:369)显著高于PSC患者(28%;AU中位数:84,p
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Autoantibodies to beta tubulin in autoimmune liver diseases-Relation to pANCA and clinical relevance.

There was evidence that perinuclear antineutrophil cytoplasmic antibodies (pANCA) in autoimmune liver diseases react with human beta-tubulin-5 (TBB5). Here, we reevaluate the specificity and clinical relevance of anti-TBB5 antibodies. Patients with untreated autoimmune hepatitis (AIH; n = 53), AIH under immunosuppressive therapy (AIH-IS; n = 125), primary sclerosing cholangitis (PSC; n = 40), primary biliary cholangitis (PBC; n = 250), nonautoimmune liver diseases (n = 158), inflammatory bowel diseases (IBD; n = 30), and healthy individuals (n = 62) were tested by enzyme-linked immunosorbent assay for IgG- and IgA-antibodies against recombinant human TBB5. pANCA were detected by immunofluorescence test. Sera were absorbed with TBB5 coupled to cyanogen bromide-activated sepharose. Prevalence and reactivity of IgG anti-TBB5 were significantly higher in patients with untreated AIH (68%; arbitrary units [AU] median: 369) than in PSC (28%; AU median: 84, P < 0.001), other liver diseases (14%; AU median: 185, P < 0.0001), IBD (3%; AU median: 111, P < 0.0001), and healthy controls (3%; AU median: 135; P < 0.0001). Anti-TBB5 did not correlate with pANCA, and immunoprecipitation with TBB5 did not abolish pANCA reactivity. In untreated AIH, anti-TBB5-reactivity was significantly higher than in AIH-IS. Transaminases decreased under IS preferentially in anti-TBB5-negative patients. There was no correlation between anti-TBB5-reactivity and histological stages. IgA-anti-TBB5 was mainly found in alcohol-associated liver disease (ALD; 39%). Our data do not support TBB5 as an autoantigenic target of pANCA. However, IgG-anti-TBB5 showed high specificity for (untreated) AIH. While they did not correlate with histological and laboratory parameters, their presence may indicate a poor response to IS.

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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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