Since cerebrospinal fluid (CSF) is an ultrafiltrate of plasma, it has much lower concentrations of the highest molecular weight proteins such as IgG, IgA and IgM. Elevated CSF IgG levels can either be the result of diffusion of plasma IgG across an altered blood brain barrier or intrathecal synthesis. Patients with multiple sclerosis and other demyelinating disorders often have elevated CSF IgG concentrations due to intrathecal synthesis. One of the best methods to detect intrathecal IgG synthesis has been to examine CSF for the presence of oligoclonal bands (OCB) after separation of proteins by electrophoresis. IgG in normal CSF migrates as a faint diffuse zone, but in demyelinating diseases, IgG migrates as multiple discrete oligoclonal bands. Oligoclonal bands are produced by a limited number of plasma cell clones, each producing IgG with its own specificity.
More than 90% of patients with multiple sclerosis have detectable oligoclonal bands in CSF. Increased IgG synthesis in the central nervous system is not specific for multiple sclerosis, but is an indication of chronic CNS inflammation. Oligoclonal bands in CSF have been reported in cases of neurosyphilis, acute bacterial or viral meningitis, progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, progressive rubella panencephalitis, polyneuritis, optic neuritis, trypanosomiasis, and other infectious or autoimmune diseases.
Oligoclonal bands are detected by isoelectric focusing on an agarose gel and subsequent immunoblotting. Unconcentrated CSF is compared directly with a serum sample run simultaneously in an adjacent track of the same agarose gel. Serum should be diluted to approximately the same IgG concentration as the CSF. Patient samples should be run in conjunction with negative and positive controls. Immunoglobulins are visualized by an IgG immunoblot. An experienced pathologist interprets the resulting patterns. Five different patterns may be observed.
|
Pattern |
Bands Observed |
Associated Diseases |
|
1 |
Polyclonal pattern (no discrete bands) in both serum & CSF |
Rare Multiple sclerosis Myelitis CNS vasculitis Paraneoplastic syndromes Systemic lupus erythematosis |
|
2 |
Same number of OCB in serum & CSF |
Myelitis CNS vasculitits Paraneoplastic syndromes Lupus CNS infections Neoplastic meningitis Behcet Disease Rasmussen Disease Hashimoto encephalitis Lymphoproliferative disorders Hepatitis C |
|
3 |
OCB in both serum & CSF CSF has at least 2 more bands than serum |
Multiple sclerosis Most CNS infections |
|
4 |
More than 2 OCB in CSF & polyclonal pattern in serum |
Most Multiple sclerosis |
|
5 |
Monoclonal band in both serum & CSF |
Normal individuals Multiple sclerosis CNS lymphoma CNS inflammatory disorders |
Patterns 3 and 4 are reported as positive for OCB. Although a single band difference between CSF and serum is not diagnostic of multiple sclerosis, more than one half of these patients will progress to a full oligoclonal pattern.
The occurrence of single monoclonal bands in CSF is uncommon. Approximately 50% of cases of monoclonal CSF bands occur without a corresponding serum band. Two thirds of patients with solitary CSF bands revert to a normal polyclonal pattern over time or retain the solitary band without evidence of disease. The remaining one third subsequently develops multiple sclerosis or another demyelinating syndrome.
Specimen requirement is a red top tube of blood and0.5 mL of CSF.
See also Multiple Sclerosis panel and Protein Electrophoresis Spinal Fluid.
References
Fortini AS, Sanders EL, Weinshenker BG, Katzmann JA. Cerebrospinal fluid oligoclonal bands in the diagnosis of multiple sclerosis. Isoelectric focusing with IgG immunoblotting compared with high-resolution agarose gel electrophoresis and cerebrospinal fluid IgG index. Am J Clin Pathol. 2003;120(5):672-675.
Thompson AJ, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173
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