An Updated Evaluation of Intrathecal IgG Synthesis Markers in Relation to Oligoclonal Bands

Abstract

The aim was to evaluate the performance of the latest quantitative marker for intrathecal IgG synthesis and to compare it with other established markers used for the same purpose. We retrospectively applied Auer’s and Reiber’s intrathecal IgG synthesis formulae in a cohort of 372 patients under investigation for central nervous system demyelination who had undergone lumbar puncture and oligoclonal bands (OCBs) detection for demonstrating intrathecal IgG synthesis. A ROC analysis revealed Auer’s formula had lower sensitivity (68%) compared to Reiber’s formula (83%) and IgG index (89%), in our cohort of patients that exhibited normal to mildly elevated albumin quotients (4.48 ± 3.93). By excluding possible sources of errors, we assume that Auer’s formula is less sensitive than other established tools for the “prediction” of the detection of OCBs in routine cerebrospinal fluid (CSF) analyses due to the mathematical model used. Given the ability of Reiber’s hyperbolic formula to describe the blood–CSF IgG distribution across a wide range of blood–brain barrier functionality, its use and the use of similar formulae are recommended for the discrimination between CNS-derived and blood-derived molecules in clinical laboratories.

Keywords

• intrathecal synthesis markers
• oligoclonal bands (OCBs)
• hyperbolic function
• multiple sclerosis (MS)
• cerebrospinal fluid (CSF) analysis
• blood-derived CSF molecules