The cerebrospinal fluid in multiple sclerosis. Quantitative assessment of intrathecal immunoglobulin synthesis by empirical formulae

Abstract

Intrathecal synthesis of IgG occurs in more than 90% of patients with clinically definite multiple sclerosis. The prevalence and significance of intrathecal synthesis of IgA and IgM are, however, less thoroughly characterized. We estimated intrathecal synthesis of IgG, IgA and IgM with various empirical formulae. The concentrations of albumin, IgG, IgA and IgM and the presence of IgG oligoclonal bands were determined in CSF and serum from 350 patients, including 97 with clinically definite multiple sclerosis. Intrathecal synthesis of IgG oligoclonal bands was detected in 95% of patients with multiple sclerosis (95% confidence interval 88–98%). The IgG‐index, an extended IgG‐index, and a hyperbolic IgG formula performed approximately equally in identifying patients with MS, but they were all inferior to the detection of IgG oligoclonal bands. In quantitative measurements, the extended immunoglobulin indices appeared to perform well; studies comparing the extended IgA‐ and IgM‐indices to qualitative analyses (electrophoresis or isoelectric focusing) are, however, needed to confirm this. Detection of intrathecal synthesis of IgA of IgM was of little value in the diagnosis of multiple sclerosis.

Intrathecal synthesis of free immunoglobulin light chains in multiple sclerosis

“…Intra-and interassay variation for albumin determinations in serum and CSF was below 5 YO. IgA and IgM concentrations in CSF and serum were determined by ELISA as previously described in detail (15). Intra-and interassay variation was below 10% for these assays.…”

Cerebrospinal fluid measures of disease activity in patients with multiple sclerosis

“…An extended a2-macroglobulin index was used as a measure of the size-selectivity of the blood-CSF protein transfer. 27 Myelin basic protein (MBP) was determined in CSF by a commercially available radioimmunoassay (DSL-1500, Diagnostic Systems Laboratories Inc., Webster, Texas). Age-dependent upper reference limits for the MBP assay were previously reported.30 In 21 patients with various nondemyelinating, noninflammatory neurological diseases, the CSF concentration of MBP was increased above these reference limits in two patients: one with cerebral metastases and one with a herniated lumbar disc, i.e., conditions associated with myelin compression.…”

Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force

“…Percentage of patients in different categories of disease with elevated IgA index, IgG index, IgM index, or non-linear intrathecal synthesis formula values[30,31,40,62,63]. Unexpected increases are more common with the IgA index, IgG index and IgM index than with corresponding nonlinear formulae…”