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Quantitative Measurement of Intrathecally Synthesized Proteins in Mice
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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
PubMed
Summary
This summary is machine-generated.

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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).
Keywords:
B burgdorferiAntibody indexCerebrospinal fluidIntrathecal antibodyLyme neuroborreliosisReiber

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  • 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.