Immunoglobulin G4(+) B-cell receptor clones distinguish immunoglobulin G 4-related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies.

Immunoglobulin G4(+) B-cell receptor clones distinguish immunoglobulin G 4-related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies.
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DOI:
10.1002/hep.28568
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发表时间:
2016-08
期刊:
影响因子:
13.5
通讯作者:
de Vries, Niek
de Vries, Niek
中科院分区:
医学1区
文献类型:
--
作者:
Doorenspleet, Marieke E.;Hubers, Lowiek M.;Culver, Emma L.;Wenniger, Lucas J. Maillette de Buy;Klarenbeek, Paul L.;Chapman, Roger W.;Baas, Frank;van de Graaf, Stan F.;Verheij, Joanne;van Gulik, Thomas M.;Barnes, Eleanor;Beuers, Ulrich;de Vries, Niek

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胆道和胰腺的免疫球蛋白G4(IgG4)相关疾病(IgG4-RD)很难与硬化性胆管炎和胆胰腺恶性肿瘤(CA)相鉴别。缺乏一种准确的非侵入性检测来诊断和监测疾病活动。我们证明,通过下一代测序确定的优势IgG4+B细胞受体(BCR)克隆可以准确地将IgG4相关性胆管炎/自身免疫性胰腺炎(n=34)患者与原发性硬化性胆管炎(n=17)和CA(n=17)患者区分开来。一种新的、更实惠的、广泛应用的定量聚合酶链式反应(QPCR)方法分析血液中IgG4/IgGRNA比率也获得了极好的诊断准确性(n=125)。此外,在敏感性(94%对86%)和特异性(99%对73%)以及与治疗反应(n=20)相关方面,这种定量聚合酶链式反应试验的表现优于血清IgG4水平。结论:IgG4+BCR克隆和IgG4/IgGRNA比值显著提高了胆道和胰腺中IgG4-RD的显示、早期诊断和监测。(《肝病》2016;:501-507)
Immunoglobulin G4 (IgG4)‐related disease (IgG4‐RD) of the biliary tree and pancreas is difficult to distinguish from sclerosing cholangitis and biliary/pancreatic malignancies (CA). An accurate noninvasive test for diagnosis and monitoring of disease activity is lacking. We demonstrate that dominant IgG4+ B‐cell receptor (BCR) clones determined by next‐generation sequencing accurately distinguish patients with IgG4‐associated cholangitis/autoimmune pancreatitis (n = 34) from those with primary sclerosing cholangitis (n = 17) and CA (n = 17). A novel, more affordable, and widely applicable quantitative polymerase chain reaction (qPCR) protocol analyzing the IgG4/IgG RNA ratio in blood also achieves excellent diagnostic accuracy (n = 125). Moreover, this qPCR test performed better than serum IgG4 levels in sensitivity (94% vs. 86%) and specificity (99% vs. 73%) and correlates with treatment response (n = 20). Conclusions: IgG4+ BCR clones and IgG4/IgG RNA ratio markedly improve delineation, early diagnosis, and monitoring of IgG4‐RD of the biliary tree and pancreas. (Hepatology 2016;64:501‐507)
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