Multiple sclerosis (MS) is a chronic inflammatory disease mainly characterized by demyelination and axonal loss. A formal diagnosis of MS is based on clinical and radiological dissemination in space and time, with an increasing role of imaging examinations. Cerebrospinal fluid (CSF) used in IgG-index testing and oligoclonal bands (OCB) are common laboratory tests used in the diagnosis of MS. In addition to MS, several other neurologic diseases generate CSF-specific OCB as a humoral immune response, along with 8% of normal individuals. We hypothesized that the measurement of immunoglobulin free light chains (FLC) in CSF could pose as an alternative to the current gold standard, labor-intensive, isoelectric-focusing gels (IEF) used for OCB. We proposed replacing OCB IEF testing with a quantitative nephelometric assay measuring CSF FLC as a more objective, less costly assay.
We compared 325 residual CSF and serum specimens with a previous order of OCB. Nephelometric measurements of kappa and lambda free light chains were generated using a Freelite® assay (The Binding Site). Cut-offs were established using receiver operator characteristic (ROC) curves with patient clinical diagnosis of demyelination after chart-review as true positives. We had a diverse group of patients with diagnosis categorized into 10 groups: demyelination (n=67), autoimmunity (n=53), non-inflammatory (n=50), inflammation (n=38), degeneration (n=28), peripheral neuropathy (n=24), infection (n=13), cancer (n=11), neuromyelitis optica (n=10), other (n=31).
A strict control group with conditions expected to be negative for OCB was used as true negatives. These included cancer, degenerative, non-inflammatory, others, and peripheral categories. Using a cut-off of 4 unique CSF bands, OCB showed a sensitivity of 86.6% and specificity of 89.6%, with a diagnostic odds ratio (OR) of 55.68. Similarly, CSF kappa FLC had a sensitivity of 85.1% and specificity of 89.6%, with OR of 49.21, when a cut-off of 0.0875mg/dL was used, eliminating the need for a paired serum sample. The combination of OCB and CSF-index as a panel had no improvement on sensitivity and specificity over OCB alone.
Measuring kappa FLC in CSF instead of performing OCB, not only establishes a quantitative value to overcome the challenges that we see with a lack of harmonization in number of positive OCB bands between institutions, but it also saves the clinical laboratory in cost each year by reducing technologist time and turn-around time from 4h to 20 min. Most importantly, it significantly reduces the pressure on the technologist involved with meticulously reading OCB patterns. We believe the clinical laboratory is ready for such a bold change. Do you?
For the complete study, see: CCLM 2018, Gurtner et al. [https://doi.org/10.1515/cclm-2017-0901]