Shunchang Li, Jifei Yao
B-type natriuretic peptide (BNP) is crucial for heart failure diagnosis. However, immunoassays are vulnerable to heterophilic antibody interference, which may lead to false-positive results and significant clinical mismanagement. Studies suggest such interference may account for a notable proportion of unexplained biomarker elevations. This report describes a case of a 36-year-old female with a markedly elevated BNP (2735.7 ± 54.3 pg/mL) incongruent with her clinical presentation. Therefore, we conducted a detailed analysis through a stepwise investigation, including serial dilution (showing non-linear recovery), cross-platform comparison (normal result on an alternative platform), and heterophilic blocking reagent treatment (partial correction). Ultimately, the addition of purified mouse IgG, but not anti-goat IgG or IgM blockers, normalized the BNP level in a dose-dependent manner, confirming human anti-mouse antibody (HAMA) interference. This case demonstrates that such interference is one of the potential causes of unexplained elevations in clinical immunoassay results. A systematic workflow was established in the case, ranging from suspicion to confirmation and ultimately to laboratory-adoptable conclusions. This process facilitates accurate diagnosis and helps clinicians avoid unnecessary interventions.