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Extreme Heterophilic Antibody Interference in BNP Immunoassay: A Case Report and Systematic Investigation Protocol
Huicong Yang1, Yuanhai Zheng1, Zhenhua Zeng1
1Department of Clinical Laboratory, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People's Republic of China.
Background:
Heterophilic antibody (HA) interference remains a persistent challenge in immunoassay diagnostics. Human anti-mouse antibodies (HAMA) can cause spuriously elevated biomarker results, potentially leading to misdiagnosis and unnecessary clinical interventions. Brain natriuretic peptide (BNP) is critical for heart failure diagnosis, but false-positive results due to HAMA may trigger inappropriate clinical management.
Case Presentation:
A 53 year-old male with type 2 diabetes presented with markedly elevated BNP (4394-4419 pg/mL; reference < 100 pg/mL) by chemiluminescence immunoassay, despite no heart failure symptoms, normal ejection fraction (62%), and normal NT-proBNP (55.8 pg/mL). This discordance prompted investigation for analytical interference.
Methods:
Serial dilution (1:4, 1:8); specific blocking with mouse IgG, goat IgG, polymeric antibodies, and RF blocker; dose-response titration of mouse IgG (200-600 μg/mL); and alternative platform comparison.
Results:
Serial dilution showed linear but incomplete recovery (R2 = 0.998), excluding hook effects. Mouse IgG induced a modest but specific 15.7% reduction in apparent BNP. Even 600 μg/mL mouse IgG achieved only partial blocking (residual BNP 2240 pg/mL), indicating high-titer HAMA exceeding standard blocking capacity.
Conclusions:
This case demonstrates extreme HAMA interference causing false-positive BNP > 4000 pg/mL. Standard blocking reagents may be insufficient for high-titer samples. When BNP is discordant with clinical status-especially with normal NT-proBNP-laboratories must use systematic verification to prevent misdiagnosis.
