1. Introduction The composition of plasma and Cerebrospinal fluid (CSF) are similar with the only major difference between the two being the greatly reduced concentration of total protein in CSF 1. The CSF is actively secreted by the four choroid plexuses and the concentration of some ions e.g. K+, are independent of the variations in the plasma concentration. CSF total protein levels are often used to support a diagnosis. Elevated levels of CSF total protein are suggestive of bacterial infection 2. Suspected meningitis / meningoencephalitis requires urgent CSF examination. It has been stated that CSF total protein determination should only be used as a screening test for meningitis 3. Method (continued) ResultsResults (continued) AACB CSF Working Party Investigation of CSF Total Protein Result Variation. G.I. Raines 1, G. Whittaker 2, M. Jenkins 3, S. Tran 4, G. Kellerman 4, M. Clough 5, J. Gill 6, S. Jovanovich 6, T. Andersen 7, D.A. Berry 8. 1 Clinical Biochemistry Unit, The Alfred, Melbourne,Vic.3004, Australia; 2 Biochemistry, Royal Prince Alfred Hospital, Sydney, Australia; 3 Biochemistry Department, Austin Pathology, Austin Health, Heidelberg VIC., Australia; 4 Clinical Chemistry, Hunter Area Pathology Service, Newcastle, NSW, Australia; 5 Clinical Chemistry, ICPMR, Westmead Hospital, Westmead, NSW, Australia; 6 RCPA-AACB Quality Assurance Programs Pty Limited, Bedford Park, SA, Australia; 7 Australian Scientific Enterprise, Sydney, Australia; 8 SEALS Sutherland Centre of Immunology, Sutherland Hospital, Caringbah, NSW, Australia. Aim The aim of the CSF working party is to improve the quality of the analytical performance of the CSF total protein assay. CSF total protein results from the RCPA QAP show distinct assay groups. The CSF Working Party conducted a survey of patient CSF samples to determine the cause of this variation in the assay results. Method Three laboratories distributed twelve unfrozen patient CSF samples. The following analysers were used: Roche Modular PPE- Lab A; Abbott Laboratories Architect ci8200- Lab B; Beckman Coulter DXC 800- Lab C; Ortho-Clinical Diagnostics Vitros Fusion 5.1- Lab D and Siemens Dimension RXL Max- Lab E. Table 1 lists the analysers, reagent and methods used in the study. They form the distinct total protein groups identified in the RCPA QAP program. Table 1. Summary of Analysers and Methods. Conclusion Patient CSF total protein results showed the same pattern of variability as seen in the RCPA CSF QAP samples. Since a ratio was used we conclude that there is no matrix effect contributing to the variation seen in the RCPA QAP reports. Thus the groups of results can be contributed to calibration or method variation and more standardisation of assays is required to improve comparability between laboratories. The procedures and methods for determination of CSF total protein are incompletely standardised and this is reflected in the lack of agreement between laboratories. Results of routine CSF total protein analysis is not disease specific. The interpretation of the results should take into account the sensitivity and specificity limitation. References 1.Brown P.D. et al. Neuroscience. 129(4) 2004: 955-968. 2.Daroriche R.O. et al. N Engl J Med. 355(19) 2006: 2012-2020. 3. Franciotta D. et al. Journal of Neurological Sciences. 237 2005: 5-11. Table 2. Summary of Calibration Material used in CSF total protein Analysis. Figure 1 Graph of RCPA QAP CSF Samples vs. CSF TP (g/l) Figure 2 Graph of Patient CSF Samples vs. CSF TP (g/l) Patient CSF samples 3, 8 and 9 were haemolysed. The mean of Lab A and Lab B results were used and a ratio was determined between this mean and the results of the other three labs. The ratio for the RCPA QAP for Lab C = 1.09; Lab D = 1.37; Lab E =1.19. The ratio for the patient CSF samples for Lab C = 1.09; Lab D = 1.37; Lab E =1.14. Table 3 Summary of the Total Protein results in g/L The following graphs summarise the results of the RCPA QAP and patient CSF samples Lab E was not able to assay four patient samples (indicated by green arrows in Fig 2).