Abstract
Background
Heterophile antibody (HAb) interferences in immunoassays can cause falsely elevated hCG concentrations leading to incorrect diagnosis and treatments options. When results are not consistent with the clinical findings, hCG HAb interference investigation may be requested by the physician. A retrospective evaluation of the frequency of HAb interference was performed among cases of physician-requested investigations and the effectiveness of commercially available blocking reagents to detect HAb interference in two immunoassay systems was evaluated.
Methods
One hundred and thirteen physician requests for hCG HAb investigation from 2008 to 2017 were reviewed. The primary method used to measure hCG was the Beckman Coulter Access Total βhCG (2008–2010) and the Roche Elecsys HCG+β (2014–2017). HAb investigation included measurement by two immunoassays before and after treatment of samples with heterophile blocking reagents and serial dilution studies.
Results
Five cases of HAb and HAb-like interference were identified. The interference frequency was 6.7% for the Beckman assay and 2.9% for the Roche assay. The presence of HAb was detected using heterophile blocking reagents and an alternative method in three cases. The other two cases were detected due to discrepant results with an alternative method and non-linear serial dilutions (HAb-like).
Conclusions
HAb interference was observed in the Beckman and the Roche assays. The heterophile blocking reagents failed to detect 40% of interference cases. Blocking reagents should not solely be used for these investigations. Multiple strategies including the use of serial dilutions and using an alternative platform are critical when troubleshooting interferences in hCG immunoassays.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Berger P, Sturgeon C. Pregnancy testing with hCG – future prospects. Trends Endocrinol Metab 2014;25:637–48.10.1016/j.tem.2014.08.004Search in Google Scholar
2. American College of Obstetricians and Gynecologist. Avoiding inappropriate clinical decision based of false positive human chorionic gonadotropin test results. ACOG Committee opinion No 278. Obstet Gynecol 2002;100:1057–9.10.1097/00006250-200211000-00044Search in Google Scholar
3. Stenman U, Alfthan H, Hotakainen K. Human chorionic gonadotropin in cancer. Clin Biochem 2004;37:549–61.10.1016/j.clinbiochem.2004.05.008Search in Google Scholar
4. Emerson JF, Lai KY. Endogenous antibody interferences in immunoassays. Lab Med 2013;44:69–73.10.1309/LMMURCFQHKSB5YECSearch in Google Scholar
5. Garcia-Gonzalez E, Aremendia M, Alvarez-Ballano D, Trincado P, Rello L. Serum sample containing endogenous antibodies interfering with multiple hormone immunoassays. Laboratory strategies to detect interference. Pract Lab Med 2016;4:1–10.10.1016/j.plabm.2015.11.001Search in Google Scholar
6. Klee GG. Interferences in hormone immunoassays. Clin Lab Med 2004;24:1–18.10.1016/j.cll.2004.01.003Search in Google Scholar
7. Levinson SS, Miller JJ. Towards a better understanding of heterophile (and the like) antibody interference with modern immunoassays. Clin Chim Acta 2002;325:1–15.10.1016/S0009-8981(02)00275-9Search in Google Scholar
8. Ward G, Simpson A, Boscato L, Hickman PE. The investigation of interferences in immunoassay. Clin Biochem 2017;50:1306–11.10.1016/j.clinbiochem.2017.08.015Search in Google Scholar PubMed
9. Kricka LJ. Human anti-animal antibody interferences in immunological assays. Clin Chem 1999;45:942–56.10.1093/clinchem/45.7.942Search in Google Scholar
10. Sturgeon CM, Berger P, Bidart JM, Birken S, Burns C, Norman RJ, et al. Differences in recognition of the 1st WHO international reference reagents for hCG-related isoforms by diagnostic immunoassays for human chorionic gonadotropin. Clin Chem 2009;55:1484–91.10.1373/clinchem.2009.124578Search in Google Scholar PubMed
11. Soares DG, Millot F, Lacroix I, Lotz JP. Heterophile antibody interference led to unneeded chemotherapy in a testicular cancer patient. Urol Case Rep 2016;9:1–3.10.1016/j.eucr.2016.07.006Search in Google Scholar PubMed PubMed Central
12. Bolstad N, Warren DJ, Nustad K. Heterophilic antibody interference in immunometric assays. Best Pract Res Clin Endocrinol Metab 2013;27:647–61.10.1016/j.beem.2013.05.011Search in Google Scholar PubMed
13. Preissner CM, Dodge LA, O’Kane DJ, Singh RJ, Grebe SK. Prevalence of heterophilic antibody interference in eight automated tumor marker immunoassays. Clin Chem 2005;51:208–10.10.1373/clinchem.2004.040501Search in Google Scholar PubMed
14. Butler SA, Cole LA. Use of heterophilic antibody blocking agent (HBT) in reducing false-positive hCG results. Clin Chem 2001;47:1332–3.10.1093/clinchem/47.7.1332Search in Google Scholar
15. Ismail AA, Walker PL, Barth JH, Lewandowski KC, Jones R, Burr WA. Wrong biochemistry results: two case reports and observational study in 5310 patients on potentially misleading thyroid-stimulating hormone and gonadotropin immunoassay results. Clin Chem 2002;48:2023–9.10.1093/clinchem/48.11.2023Search in Google Scholar
16. Cole LA. Human chorionic gonadotropin (hCG) and hyperglycosylated hCG, seven semi-independent critical molecules: a review. J Mol Oncol Res 2017;1:22–44.Search in Google Scholar
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