Lacombe Valentin, Urbanski Geoffrey
Service de Médecine interne et polyvalente, 708873 Centre Hospitalier du Haut-Anjou , Château-Gontier, France.
Service de Médecine interne et immunologie clinique, Centre Hospitalier Universitaire d'Angers, Angers, France.
Clin Chem Lab Med. 2025 Sep 5. doi: 10.1515/cclm-2025-0671.
Pernicious anemia (PA) is a common cause of vitamin B12 deficiency and requires a robust diagnosis to guide lifelong treatment. Anti-parietal cell antibodies (APCA) are frequently used as a diagnostic marker, but their poor specificity raises concerns about overdiagnosis, particularly in patients lacking the more specific but less sensitive anti-intrinsic factor antibodies (IFA). We compared the diagnostic performance of two APCA detection methods: indirect immunofluorescence (IIF) and immunodot assay.
We prospectively enrolled patients with B12 deficiency and APCA positivity without IFA. PA diagnosis was adjudicated by blinded expert based on histology and response to oral B12. Patients were classified as true PA (APCA-PA), false positive (APCA-FP), or undetermined. Only APCA-PA and APCA-FP cases were analyzed.
Among 56 included patients, 19 were classified as APCA-PA and compared to 24 APCA-FP. APCA immunodot assay was positive in 19/19 APCA-PA vs. 23/24 APCA-FP (p>0.99), while APCA IIF was positive in 13/19 APCA-PA vs. 2/24 APCA-FP (p<0.001), with higher IIF titers among APCA-PA (p<0.001). Only IIF positivity was significantly associated with PA (68.4 % vs. 8.3 %, p<0.001), with 92 % specificity. This association was confirmed in multivariate analysis (OR 37.1 [95 % CI: 6.1-439.4]). APCA IIF titer was also associated with PA diagnosis (AUC 0.82 [95 % CI: 0.68-0.96]), and titer ≥1:80 further improved specificity to 96 %.
IIF is more specific than immunodot for PA diagnosis, and its result should prevail over immunodot when deciding whether to perform EGD, when EGD is not feasible, and when establishing the diagnosis if biopsies are inconclusive.
恶性贫血（PA）是维生素B12缺乏的常见原因，需要进行可靠的诊断以指导终身治疗。抗壁细胞抗体（APCA）常被用作诊断标志物，但其特异性较差引发了对过度诊断的担忧，尤其是在缺乏更具特异性但敏感性较低的抗内因子抗体（IFA）的患者中。我们比较了两种APCA检测方法的诊断性能：间接免疫荧光法（IIF）和免疫斑点法。
我们前瞻性纳入了维生素B12缺乏且APCA阳性但无IFA的患者。PA诊断由盲法专家根据组织学和对口服维生素B12的反应进行判定。患者被分类为真性PA（APCA-PA）、假阳性（APCA-FP）或未确定。仅分析APCA-PA和APCA-FP病例。
在纳入的56例患者中，19例被分类为APCA-PA，24例为APCA-FP。APCA免疫斑点法在19/19例APCA-PA中呈阳性，而在23/24例APCA-FP中呈阳性（p>0.99），而APCA IIF在13/19例APCA-PA中呈阳性，在2/24例APCA-FP中呈阳性（p<0.001），APCA-PA中的IIF滴度更高（p<0.001）。仅IIF阳性与PA显著相关（68.4%对8.3%，p<0.001），特异性为92%。多因素分析证实了这种关联（比值比37.1[95%置信区间：6.1-439.4]）。APCA IIF滴度也与PA诊断相关（曲线下面积0.82[95%置信区间：0.68-0.96]），滴度≥1:80可进一步将特异性提高至96%。
IIF在PA诊断中比免疫斑点法更具特异性，在决定是否进行内镜检查、内镜检查不可行以及活检结果不明确时进行诊断时，其结果应优先于免疫斑点法。
