Bansi D S, Bauducci M, Bergqvist A, Boberg K, Broome U, Chapman R, Fleming K, Jorgensen R, Lindor K, Rosina F, Schrumpf E
Department of Gastroenterology, John Radcliffe Hospital, Oxford, UK.
Eur J Gastroenterol Hepatol. 1997 Jun;9(6):575-80. doi: 10.1097/00042737-199706000-00005.
The reported prevalence of antineutrophil cytoplasmic antibodies (ANCA) in primary sclerosing cholangitis (PSC) varies considerably (26-85%). Part of this may reflect methodological differences but part may reflect the differences in the patient groups analysed. To resolve this issue we compared the sensitivity and specificity of the immunoalkaline phosphatase (IALP) and immunofluorescence (IF) techniques in four different populations.
Sera from four centres were tested blind on alcohol-fixed neutrophils using both techniques.
USA: 14 PSC, 14 primary biliary cirrhosis (PBC); Sweden: 32 PSC, 3 autoimmune hepatitis (AIH), 14 PBC, 11 chronic liver disease; Norway: 32 PSC, 14 AIH, 13 PBC, 1 hepatitis C. Italy: 8 PSC, 14 PBC, 8 viral hepatitis. Thirty-six normal healthy volunteers from Oxford, together with positive and negative controls, were also tested.
The healthy controls were all ANCA negative. The diagnostic sensitivity and specificity, respectively, of ANCA for PSC using the IALP technique for the different test sera were: USA 71% and 93%, Sweden 66% and 96%, Norway 69% and 46%, Italy 50% and 95%. The diagnostic sensitivity and specificity, respectively, of the IF technique on the same sera were: USA 50% and 86%, Sweden 56% and 86%, Norway 47% and 61%, Italy 50% and 91%. Overall, combining all four groups, detection of ANCA using the IALP technique gave a diagnostic sensitivity of 66% with a specificity of 74% for PSC. In contrast, the IF technique gave an overall diagnostic of only 51% (P = 0.044, compared with IALP) with a specificity of 73%. Although overall the IALP technique was more sensitive than IF, the differences in sensitivity and specificity between the two techniques did not reach statistical significance for any individual group. Furthermore, the small differences in sensitivity between the four groups using either technique were not significant. However, the IALP technique had greater specificity in the US, Swedish and Italian groups compared with the Norwegian group (P < 0.05) whereas no statistically significant differences in specificity were noted between the groups using the IF technique.
This study shows that the IALP method of ANCA detection is at least as sensitive as IF for the serological diagnosis of PSC. Indeed, combining data from all four centres, the IALP technique was significantly more sensitive than IF. We therefore recommend the use of the IALP technique, which is also easier to interpret and does not require the use of a specialist fluorescent microscope. The lack of a wide variation in sensitivity between IALP and IF for any individual patient group reported in this study suggests that the previously reported regional differences in ANCA prevalence in PSC of between 26% and 85% may be patient, related, rather than due to ethnic or methodological differences in ANCA detection, perhaps reflecting possible disease heterogeneity within PSC, or case selection bias. Further studies are needed to investigate this intriguing possibility. Such differences, if confirmed, will need to be taken into account when assessing the use of ANCA as a serological marker of PSC.
原发性硬化性胆管炎（PSC）中抗中性粒细胞胞浆抗体（ANCA）的报道患病率差异很大（26%-85%）。部分原因可能是方法学差异，但部分可能反映了所分析患者群体的差异。为解决这一问题，我们比较了免疫碱性磷酸酶（IALP）和免疫荧光（IF）技术在四个不同人群中的敏感性和特异性。
使用这两种技术对来自四个中心的血清在酒精固定的中性粒细胞上进行盲法检测。
美国：14例PSC，14例原发性胆汁性肝硬化（PBC）；瑞典：32例PSC，3例自身免疫性肝炎（AIH），14例PBC，11例慢性肝病；挪威：32例PSC，14例AIH，13例PBC，1例丙型肝炎。意大利：8例PSC，14例PBC，8例病毒性肝炎。还对来自牛津的36名正常健康志愿者以及阳性和阴性对照进行了检测。
健康对照者的ANCA均为阴性。使用IALP技术对不同检测血清中PSC的ANCA诊断敏感性和特异性分别为：美国71%和93%，瑞典66%和96%，挪威69%和46%，意大利50%和95%。对相同血清使用IF技术的诊断敏感性和特异性分别为：美国50%和86%，瑞典56%和86%，挪威47%和61%，意大利50%和91%。总体而言，综合所有四组，使用IALP技术检测ANCA对PSC的诊断敏感性为66%，特异性为74%。相比之下，IF技术的总体诊断率仅为51%（与IALP相比，P = 0.044），特异性为73%。虽然总体上IALP技术比IF更敏感，但两种技术之间的敏感性和特异性差异在任何单个组中均未达到统计学意义。此外，使用任何一种技术的四组之间敏感性的微小差异也不显著。然而，与挪威组相比，IALP技术在美国、瑞典和意大利组中具有更高的特异性（P < 0.05），而使用IF技术的组之间在特异性方面未观察到统计学显著差异。
本研究表明，IALP法检测ANCA对PSC的血清学诊断至少与IF一样敏感。实际上，综合四个中心的数据，IALP技术比IF显著更敏感。因此，我们建议使用IALP技术，该技术也更易于解读，且无需使用专业荧光显微镜。本研究中任何单个患者组IALP和IF之间敏感性缺乏广泛差异表明，先前报道的PSC中ANCA患病率的地区差异在26%至85%之间可能与患者有关，而非由于ANCA检测中的种族或方法学差异，这可能反映了PSC内可能的疾病异质性或病例选择偏倚。需要进一步研究来调查这种有趣的可能性。如果证实存在此类差异，在评估将ANCA用作PSC的血清学标志物时将需要考虑这些差异。
