Not all anti-parietal cell antibody tests are equal for diagnosing pernicious anemia
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Valentin Lacombe
and
Geoffrey Urbanski
Abstract
Objectives
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.
Methods
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.
Results
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 %.
Conclusions
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.
Funding source: Centre Hospitalier Universitaire d’Angers
Award Identifier / Grant number: Appel d’offre interne (2020)
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Research ethics: This study was approved by the Angers University Hospital Bioethics Committee (2018/63), and was study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).
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Informed consent: All participants provided written informed consent.
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Author contributions: VL: conceptualization, methodology, investigation, data curation, formal analysis, writing – original draft. GU: conceptualization, methodology, funding acquisition, supervision, formal analysis, writing – review and editing. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: LLM was used solely to improve the clarity and accuracy of the English language in the writing of this manuscript. No LLM or deep learning tool was involved in the generation, analysis, or interpretation of any data presented in the study.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: This study received funding support from the University Hospital of Angers.
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Data availability: The data that support the findings of this study are available from the corresponding author (VL) upon reasonable request.
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