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Updated: Jun 6, 2026

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Quantitative Measurement of Intrathecally Synthesized Proteins in Mice
Published on: November 29, 2019
Intrathecal antibody synthesis - Reiber method revisited
John J Halperin1,2, Dane Granger3
1Department of Neurology, Atlantic Health Overlook Medical Center, Summit, NJ, 07901, USA. John.halperin@atlantichealth.org.
BMC Neurology
|June 4, 2026
Summary
Linear models better quantify central nervous system inflammation than the Reiber hyperbolic model for diagnosing diseases like Lyme. New cutoffs improve accuracy for immunoglobulin G index and synthesis assessments.
Area of Science:
- Neurology
- Immunology
- Biostatistics
Background:
- Cerebrospinal fluid (CSF) immunoglobulin G (IgG) analysis aids in diagnosing central nervous system (CNS) inflammatory diseases.
- Common methods include qualitative oligoclonal bands (OCBs) and quantitative CSF:serum IgG:albumin ratios (e.g., IgG index).
- Laboratories in the US typically use linear models, while European labs often use Reiber's hyperbolic model.
Purpose of the Study:
- To compare the diagnostic accuracy of linear and Reiber hyperbolic models for assessing excess CSF IgG.
- To evaluate the performance of both models in relation to OCBs and Lyme-specific antibody indices (AI).
Main Methods:
- Compared linear and Reiber hyperbolic models using data from 1,872 CSF samples (1,365 with Lyme-specific data).
- Assessed correlations with OCBs using Receiver Operating Characteristic (ROC) analysis.
- Compared Lyme-specific antibody indices calculated by both methods.
Main Results:
- Linear regression showed a strong correlation (r=0.98) in normal samples and a robust correlation (r=0.95) in abnormal samples.
- Linear models demonstrated stronger associations with OCBs (ROC AUC 0.81) compared to the Reiber model (ROC AUC 0.74).
- Reiber model modification was applicable in only 14.7% of Lyme AI analyses, with minimal impact on diagnostic conclusions.
Conclusions:
- Linear models more accurately reflect intra-CNS inflammation and are recommended for diagnosing CNS inflammatory diseases.
- ROC-derived cutoffs for IgG index and IgG synthesis provide more accurate assessments of CSF immunoreactivity.
- The Reiber hyperbolic model, despite its complexity, functions linearly within the clinically relevant range.

