[False positive of DUPAN-2 caused by IgM-human anti mouse antibody]
Masaki Abe1, Miyuki Hyoki, Ikurou Abe
1Central Clinical Laboratory, Jikei University Hospital, Minato-ku, Tokyo 105-8471, Japan. ma_abe@jikei.ac.jp
Insights
A false-positive result for the DUPAN-2 cancer marker was identified in a patient due to IgM-human anti-mouse antibody (HAMA) activity. This HAMA in the patient
Area of Science:
- Clinical Chemistry
- Immunology
- Oncology Diagnostics
Background:
- DUPAN-2 is a tumor-associated antigen used in cancer diagnostics.
- Human anti-mouse antibody (HAMA) interference can cause inaccurate immunoassay results.
- Understanding assay interferences is crucial for accurate clinical interpretation.
Observation:
- A 40s female patient exhibited persistently elevated DUPAN-2 levels (up to 770 U/mL) unexplained by clinical or radiological findings.
- Standard tests showed no dilution linearity, but absorption tests indicated interference primarily with IgM.
- Specific immunological assays suggested patient's IgM, with HAMA activity, reacted with mouse monoclonal antibodies in the DUPAN-2 assay reagents.
Findings:
- The elevated DUPAN-2 levels were confirmed as a false-positive phenomenon.
- The mechanism involved the patient's IgM-HAMA cross-reacting with mouse monoclonal antibodies used in the DUPAN-2 assay.
- High-performance liquid chromatography (HPLC) analysis showed the patient's DUPAN-2 eluted in the IgM fraction, unlike controls.
Implications:
- This case highlights the potential for IgM-HAMA to cause false-positive DUPAN-2 results.
- Clinicians should consider HAMA interference when DUPAN-2 levels are unexpectedly high and inconsistent with clinical presentation.
- Further investigation into immunoassay interferences is necessary for reliable tumor marker testing.
Abstract:
We investigated a case in our experience presenting false-positive for DUPAN-2 by IgM-human anti mouse antibody (HAMA). A female aged 40s has been treated in our hospital from 2003. Her serum level of DUPAN-2 in 2005 and 2006 were 110 U/mL and 140 U/mL respectively. While this level was increased to 770 U/ml in 2007, and kept in the higher level so far. Around years of 2007, no meaning changes was detected by radiological and laboratory tests, and there was no significant change in her clinical signs and symptoms and medications. The elevation of DUPAN-2 was thought as a false-positive phenomenon and the mechanism was investigated. As results, no dilution lineality was found, and absorption test showed a 95% reduction of DUPAN-2 levels not by IgG and IgA, but IgM-specific antiserum. Dithiothreitoldeacylation test with neuraminidase, and absorption test with HBR-1, IIR, and mouse IgM serum, it was suggested that the IgM with HAMA activity of the patient reacted with mouse monoclonal antibodies in reagents. Moreover, the HPLC-eluted fraction of DUPAN-2 of this patients was detected in the fraction of IgM, which as different from that of a control pancreatic cancer patient. Above these data, elevation of DUPAN-2 in this patient was a false positive phenomenon by IgM-HAMA reacting with mouse monoclonal antibodies in reagents. Although there are few reported cases of false positive phenomenon in DUPAN-2 measurement, we have to pay attention to such phenomenon when detecting an unlikely higher levels that could not be explained by clinical information.
