Evaluation of high resolution gel β2-transferrin for detection of cerebrospinal fluid leak
-
Christopher R. McCudden
, Brent A. Senior
Abstract
Background: Cerebrospinal fluid (CSF) leaks are potentially life-threatening conditions that can be diagnosed by detection of β2-transferrin using protein electrophoresis. Another less commonly available test is β-trace protein quantitation using immunoassay. The objectives of this study were to evaluate a new immunofixation-based β2-transferrin test for detection of CSF leaks and to compare it to an existing agarose gel electrophoresis test and β-trace protein immunoassay.
Methods: For method comparison, 63 consecutive samples from physician-ordered β2-transferrin tests were analyzed using two different electrophoresis methods, agarose gel fractionation followed by acid-violet staining, and high resolution agarose gel electrophoresis followed by β2-transferrin immunofixation. A subset of samples (16/63) were analyzed for β-trace protein. Results were compared against patient chart data for the presence of a CSF leak. Additional studies were performed to assess the stability, detection limit, and analytical specificity of the β2-transferrin immunofixation test.
Results: The β2-transferrin immunofixation test had a sensitivity of 100% (40/40) and specificity of 71% (12/17) for detection of CSF leaks. By comparison, the agarose gel test had a sensitivity of 87% (35/40) and specificity of 94% (16/17). β-trace protein had a sensitivity of 100% (10/10) and specificity of 86% (5/6). Serum and saliva could be differentiated from CSF by the β2-transferrin immunofixation test based on their migration patterns. However, whole blood samples appeared positive for β2-transferrin at a threshold of ∼4 g/L hemoglobin. At a cut-off of 3 mg/L, β-trace protein was increased in 10/10 cases with documented CSF leak and in 1/6 patients without CSF leak.
Conclusions: Both the new immunofixation test for β2-transferrin and the β-trace protein were effective at detecting CSF leaks. Users of the β2-transferrin immunofixation test should be cautioned against interpreting samples with blood contamination.
We gratefully acknowledge Sebia, USA for providing β2-transferrin immunofixation kits.
Conflict of interest statement
Author’s conflict of interest disclosure: The author stated that there are no conflicts of interest regarding the publication of this article.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
References
1. Görögh T, Rudolph P, Meyer JE, Werner JA, Lippert BM, Maune S. Separation of beta2-transferrin by denaturing gel electrophoresis to detect cerebrospinal fluid in ear and nasal fluids. Clin Chem 2005;51:1704–10.10.1373/clinchem.2005.054916Search in Google Scholar
2. Papadea C, Schlosser RJ. Rapid method for beta2-transferrin in cerebrospinal fluid leakage using an automated immunofixation electrophoresis system. Clin Chem 2005;51:464–70.10.1373/clinchem.2004.042697Search in Google Scholar
3. Schnabel C, Di Martino E, Gilsbach JM, Riediger D, Gressner AM, Kunz D. Comparison of beta2-transferrin and beta-trace protein for detection of cerebrospinal fluid in nasal and ear fluids. Clin Chem 2004;50:661–3.10.1373/clinchem.2003.024158Search in Google Scholar PubMed
4. Bachmann G, Nekic M, Michel O. Clinical experience with beta-trace protein as a marker for cerebrospinal fluid. Ann Otol Rhinol Laryngol 2000;109:1099–102.10.1177/000348940010901202Search in Google Scholar PubMed
5. Burkhard PR, Rodrigo N, May D, Sztajzel R, Sanchez JC, Hochstrasser DF, et al. Assessing cerebrospinal fluid rhinorrhea: a two-dimensional electrophoresis approach. Electrophoresis 2001;22:1826–33.10.1002/1522-2683(200105)22:9<1826::AID-ELPS1826>3.0.CO;2-LSearch in Google Scholar PubMed
6. Marshall AH, Jones NS, Robertson IJ. An algorithm for the management of CSF rhinorrhoea illustrated by 36 cases. Rhinology 1999;37:182–5.Search in Google Scholar PubMed
7. Meco C, Oberascher G. Comprehensive algorithm for skull base dural lesion and cerebrospinal fluid fistula diagnosis. Laryngoscope 2004;114:991–9.10.1097/00005537-200406000-00007Search in Google Scholar PubMed
8. Payne RJ, Frenkiel S, Glikstein R, Mohr G. Role of computed tomographic cisternography in the management of cerebrospinal fluid rhinorrhea. J Otolaryngol 2003;32:93–100.10.2310/7070.2003.37260Search in Google Scholar PubMed
9. Zapalac JS, Marple BF, Schwade ND. Skull base cerebrospinal fluid fistulas: a comprehensive diagnostic algorithm. Otolaryngol Head Neck Surg 2002;126:669–76.10.1067/mhn.2002.125755Search in Google Scholar PubMed
10. Sanders EL, Clark RJ, Katzmann JA. Cerebrospinal fluid leakage: agarose gel electrophoresis detection of beta(2)-transferrin and nephelometric quantification of beta-trace protein. Clin Chem 2004;50:2401–3.10.1373/clinchem.2004.040246Search in Google Scholar PubMed
11. Grantham VV, Blakley B, Winn J. Technical review and considerations for a cerebrospinal fluid leakage study. J Nucl Med Technol 2006;34:48–51.Search in Google Scholar PubMed
12. Normansell DE, Stacy EK, Booker CF, Butler TZ. Detection of beta-2 transferrin in otorrhea and rhinorrhea in a routine clinical laboratory setting. Clin Diagn Lab Immunol 1994;1: 68–70.10.1128/cdli.1.1.68-70.1994Search in Google Scholar
13. Bachmann G, Petereit H. Beta-trace protein as sensitive marker for liquorrhea. Acta Neurol Scand 2004;110:337–8; author reply 339.10.1111/j.1600-0404.2004.00318.xSearch in Google Scholar PubMed
14. Canty A, Ripley BD. Boot: Bootstrap R (S-Plus) Functions; 2-01. R package version 1.3-4.Search in Google Scholar
15. Davison AC, Hinkley DV. Bootstrap methods and their applications. Cambridge: Cambridge University Press, 1997.10.1017/CBO9780511802843Search in Google Scholar
16. Team RDC. R: A language and environment for statistical computing 2011.Search in Google Scholar
17. Snyder JA, Rogers MW, King MS, Phillips JC, Chapman JF, Hammett-Stabler CA. The impact of hemolysis on Ortho-Clinical Diagnostic’s ECi and Roche’s elecsys immunoassay systems. Clin Chim Acta 2004;348:181–7.10.1016/j.cccn.2004.05.017Search in Google Scholar PubMed
18. Reiber H. Beta-trace protein concentration in nasal secretion: discrepancies and flaws in recent publications. Acta Neurol Scand 2004;110:339–41.10.1111/j.1600-0404.2004.00317.xSearch in Google Scholar
19. Reiber H, Walther K, Althaus H. Beta-trace protein as sensitive marker for CSF rhinorhea and CSF otorhea. Acta Neurol Scand 2003;108:359–62.10.1034/j.1600-0404.2003.00173.xSearch in Google Scholar PubMed
20. Bachmann G, Petereit H, Djenabi U, Michel O. Predictive values of beta-trace protein (prostaglandin D synthase) by use of laser-nephelometry assay for the identification of cerebrospinal fluid. Neurosurgery 2002;50:571–6; discussion 576–7.10.1227/00006123-200203000-00027Search in Google Scholar
21. Buchman CA, Luxford WM, Hirsch BE, Fucci MJ, Kelly RH. Beta-2 transferrin assay in the identification of perilymph. Am J Otol 1999;20:174–8.Search in Google Scholar
©2013 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Letters to the Editor
- Performance evaluation of three different immunoassays for detection of antibodies to hepatitis B core
- Serum homocysteine concentrations in Chinese children with autism
- Interchangeability of venous and capillary HbA1c results is affected by oxidative stress
- Interference of hemoglobin (Hb) N-Baltimore on measurement of HbA1c using the HA-8160 HPLC method
- First human isolate of Mycobacterium madagascariense in the sputum of a patient with tracheobronchitis
- Protein S and protein C measurements should not be undertaken during vitamin K antagonist therapy
- α2-HS glycoprotein is an essential component of cryoglobulin associated with chronic hepatitis C
- An unusual interference in CK MB assay caused by a macro enzyme creatine phosphokinase (CK) type 2 in HIV-infected patients
- An automated technique for the measurement of the plasma glutathione reductase activity and determination of reference limits for a healthy population
- Is osteopontin stable in plasma and serum?
- Evidence-based approach to reducing perceived wasteful practices in laboratory medicine
- Masthead
- Masthead
- Editorials
- Testing volume is not synonymous of cost, value and efficacy in laboratory diagnostics
- Lessons from controversy: biomarkers evaluation
- Commercial immunoassays in biomarkers studies: researchers beware!1)
- Trials and tribulations in lupus anticoagulant testing
- Reviews
- Mass spectrometry: a revolution in clinical microbiology?
- Chronic Chagas disease: from basics to laboratory medicine
- General Clinical Chemistry and Laboratory Medicine
- Shop for quality or quantity? Volumes and costs in clinical laboratories
- Minor improvement of venous blood specimen collection practices in primary health care after a large-scale educational intervention
- Evaluation of high resolution gel β2-transferrin for detection of cerebrospinal fluid leak
- Serum kallikrein-8 correlates with skin activity, but not psoriatic arthritis, in patients with psoriatic disease
- Soluble urokinase plasminogen activator receptor (suPAR) in the assessment of inflammatory activity of rheumatoid arthritis patients in remission
- Bone mass density selectively correlates with serum markers of oxidative damage in post-menopausal women
- Validation of a fast and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) with atmospheric pressure chemical ionization method for simultaneous quantitation of voriconazole, itraconazole and its active metabolite hydroxyitraconazole in human plasma
- Performance of different screening methods for the determination of urinary glycosaminoclycans
- Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow’s milk allergy in toddlers
- An internal validation approach and quality control on hematopoietic chimerism testing after allogeneic hematopoietic cell transplantation
- Serum levels of IgG antibodies against oxidized LDL and atherogenic indices in HIV-1-infected patients treated with protease inhibitors
- Cooperation experience in a multicentre study to define the upper limits in a normal population for the diagnostic assessment of the functional lupus anticoagulant assays
- Contribution of procoagulant phospholipids, thrombomodulin activity and thrombin generation assays as prognostic factors in intensive care patients with septic and non-septic organ failure
- Suitability of POC lactate methods for fetal and perinatal lactate testing: considerations for accuracy, specificity and decision making criteria
- Point-of-care testing on admission to the intensive care unit: lactate and glucose independently predict mortality
- Reference Values and Biological Variations
- CA125 reference values change in male and postmenopausal female subjects
- Distributions and ranges of values of blood and urinary biomarker of inflammation and oxidative stress in the workers engaged in office machine manufactures: evaluation of reference values
- Cancer Diagnostics
- Association of acute phase protein-haptoglobin, and epithelial-mesenchymal transition in buccal cancer: a preliminary report
- Comparison of diagnostic and prognostic performance of two assays measuring thymidine kinase 1 activity in serum of breast cancer patients
- Evaluation of the BRAHMS Kryptor® Thyroglobulin Minirecovery Test in patients with differentiated thyroid carcinoma
Articles in the same Issue
- Letters to the Editor
- Performance evaluation of three different immunoassays for detection of antibodies to hepatitis B core
- Serum homocysteine concentrations in Chinese children with autism
- Interchangeability of venous and capillary HbA1c results is affected by oxidative stress
- Interference of hemoglobin (Hb) N-Baltimore on measurement of HbA1c using the HA-8160 HPLC method
- First human isolate of Mycobacterium madagascariense in the sputum of a patient with tracheobronchitis
- Protein S and protein C measurements should not be undertaken during vitamin K antagonist therapy
- α2-HS glycoprotein is an essential component of cryoglobulin associated with chronic hepatitis C
- An unusual interference in CK MB assay caused by a macro enzyme creatine phosphokinase (CK) type 2 in HIV-infected patients
- An automated technique for the measurement of the plasma glutathione reductase activity and determination of reference limits for a healthy population
- Is osteopontin stable in plasma and serum?
- Evidence-based approach to reducing perceived wasteful practices in laboratory medicine
- Masthead
- Masthead
- Editorials
- Testing volume is not synonymous of cost, value and efficacy in laboratory diagnostics
- Lessons from controversy: biomarkers evaluation
- Commercial immunoassays in biomarkers studies: researchers beware!1)
- Trials and tribulations in lupus anticoagulant testing
- Reviews
- Mass spectrometry: a revolution in clinical microbiology?
- Chronic Chagas disease: from basics to laboratory medicine
- General Clinical Chemistry and Laboratory Medicine
- Shop for quality or quantity? Volumes and costs in clinical laboratories
- Minor improvement of venous blood specimen collection practices in primary health care after a large-scale educational intervention
- Evaluation of high resolution gel β2-transferrin for detection of cerebrospinal fluid leak
- Serum kallikrein-8 correlates with skin activity, but not psoriatic arthritis, in patients with psoriatic disease
- Soluble urokinase plasminogen activator receptor (suPAR) in the assessment of inflammatory activity of rheumatoid arthritis patients in remission
- Bone mass density selectively correlates with serum markers of oxidative damage in post-menopausal women
- Validation of a fast and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) with atmospheric pressure chemical ionization method for simultaneous quantitation of voriconazole, itraconazole and its active metabolite hydroxyitraconazole in human plasma
- Performance of different screening methods for the determination of urinary glycosaminoclycans
- Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow’s milk allergy in toddlers
- An internal validation approach and quality control on hematopoietic chimerism testing after allogeneic hematopoietic cell transplantation
- Serum levels of IgG antibodies against oxidized LDL and atherogenic indices in HIV-1-infected patients treated with protease inhibitors
- Cooperation experience in a multicentre study to define the upper limits in a normal population for the diagnostic assessment of the functional lupus anticoagulant assays
- Contribution of procoagulant phospholipids, thrombomodulin activity and thrombin generation assays as prognostic factors in intensive care patients with septic and non-septic organ failure
- Suitability of POC lactate methods for fetal and perinatal lactate testing: considerations for accuracy, specificity and decision making criteria
- Point-of-care testing on admission to the intensive care unit: lactate and glucose independently predict mortality
- Reference Values and Biological Variations
- CA125 reference values change in male and postmenopausal female subjects
- Distributions and ranges of values of blood and urinary biomarker of inflammation and oxidative stress in the workers engaged in office machine manufactures: evaluation of reference values
- Cancer Diagnostics
- Association of acute phase protein-haptoglobin, and epithelial-mesenchymal transition in buccal cancer: a preliminary report
- Comparison of diagnostic and prognostic performance of two assays measuring thymidine kinase 1 activity in serum of breast cancer patients
- Evaluation of the BRAHMS Kryptor® Thyroglobulin Minirecovery Test in patients with differentiated thyroid carcinoma