Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
Hepatology. 2014 May;59(5):1954-63. doi: 10.1002/hep.26977. Epub 2014 Apr 1.
The recent addition of immunoglobulin (Ig)G4-associated cholangitis (IAC), also called IgG4-related sclerosing cholangitis (IRSC), to the spectrum of chronic cholangiopathies has created the clinical need for reliable methods to discriminate between IAC and the more common cholestatic entities, primary (PSC) and secondary sclerosing cholangitis. The current American Association for the Study of Liver Diseases practice guidelines for PSC advise on the measurement of specific Ig (sIg)G4 in PSC patients, but interpretation of elevated sIgG4 levels remains unclear. We aimed to provide an algorithm to distinguish IAC from PSC using sIgG analyses. We measured total IgG and IgG subclasses in serum samples of IAC (n = 73) and PSC (n = 310) patients, as well as in serum samples of disease controls (primary biliary cirrhosis; n = 22). sIgG4 levels were elevated above the upper limit of normal (ULN = >1.4 g/L) in 45 PSC patients (15%; 95% confidence interval [CI]: 11-19). The highest specificity and positive predictive value (PPV; 100%) for IAC were reached when applying the 4 × ULN (sIgG4 > 5.6 g/L) cutoff with a sensitivity of 42% (95% CI: 31-55). However, in patients with a sIgG4 between 1 × and 2 × ULN (n = 38/45), the PPV of sIgG4 for IAC was only 28%. In this subgroup, the sIgG4/sIgG1 ratio cutoff of 0.24 yielded a sensitivity of 80% (95% CI: 51-95), a specificity of 74% (95% CI: 57-86), a PPV of 55% (95% CI: 33-75), and a negative predictive value of 90% (95% CI: 73-97).
Elevated sIgG4 (>1.4 g/L) occurred in 15% of patients with PSC. In patients with a sIgG4 >1.4 and <2.8 g/L, incorporating the IgG4/IgG1 ratio with a cutoff at 0.24 in the diagnostic algorithm significantly improved PPV and specificity. We propose a new diagnostic algorithm based on IgG4/IgG1 ratio that may be used in clinical practice to distinguish PSC from IAC.
提供一种使用 sIgG 分析区分 IAC 与 PSC 的算法。
我们测量了 IAC（n = 73）和 PSC（n = 310）患者以及疾病对照者（原发性胆汁性胆管炎；n = 22）血清样本中的总 IgG 和 IgG 亚类。45 例 PSC 患者（15%；95%置信区间 [CI]：11-19）的 sIgG4 水平高于正常值上限（ULN = >1.4 g/L）。当应用 4×ULN（sIgG4 >5.6 g/L）截断值时，对 IAC 的特异性和阳性预测值（PPV；100%）最高，敏感性为 42%（95%CI：31-55）。然而，在 sIgG4 处于 1×至 2×ULN 之间的患者（n = 38/45）中，sIgG4 对 IAC 的 PPV 仅为 28%。在这个亚组中，sIgG4/sIgG1 比值截断值为 0.24，其敏感性为 80%（95%CI：51-95），特异性为 74%（95%CI：57-86），PPV 为 55%（95%CI：33-75），阴性预测值为 90%（95%CI：73-97）。
15%的 PSC 患者 sIgG4 升高（>1.4 g/L）。在 sIgG4 >1.4 和 <2.8 g/L 的患者中，将 IgG4/IgG1 比值与 0.24 的截断值纳入诊断算法，可显著提高 PPV 和特异性。我们提出了一种新的基于 IgG4/IgG1 比值的诊断算法，可用于临床实践中区分 PSC 和 IAC。
