CSF free light chain identification of demyelinating disease: Comparison with oligoclonal banding and other CSF indexes

Kari M. Gurtner, Eslam Shosha, Sandra C. Bryant, Bruna D. Andreguetto, David L. Murray, Sean J Pittock, Maria Alice V. Willrich

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Cerebrospinal fluid (CSF) used in immunoglobulin gamma (IgG) index testing and oligoclonal bands (OCBs) are common laboratory tests used in the diagnosis of multiple sclerosis. The measurement of CSF free light chains (FLC) could pose as an alternative to the labor-intensive isoelectric-focusing (IEF) gels used for OCBs. A total of 325 residual paired CSF and serum specimens were obtained after physician-ordered OCB IEF testing. CSF kappa (cKFLC) and lambda FLC (cLFLC), albumin and total IgG were measured. Calculations were performed based on combinations of analytes: CSF sum of kappa and lambda ([cKFLC+cLFLC]), kappa-index (K-index) ([cKFLC/sKFLC]/[CSF albumin/serum albumin]), kappa intrathecal fraction (KFLCIF) {([cKFLC/sKFLC]-[0.9358×CSF albumin/serum albumin]^[0.6687×sKFLC]/cKFLC)} and IgG-index ([CSF IgG/CSF albumin]/[serum IgG/serum albumin]). Patients were categorized as: 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) and others (n=31). cKFLC measurement used alone at a cutoff of 0.0611 mg/dL showed >90% agreement to OCBs, similar or better performance than all other calculations, reducing the number of analytes and variables. When cases of demyelinating disease were reviewed, cKFLC measurements showed 86% clinical sensitivity/77% specificity. cKFLC alone demonstrates comparable performance to OCBs along with increased sensitivity for demyelinating diseases. Replacing OCB with cKFLC would alleviate the need for serum and CSF IgG and albumin and calculated conversions. cKFLC can overcome challenges associated with performance, interpretation, and cost of traditional OCBs, reducing costs and maintaining sensitivity and specificity supporting MS diagnosis.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StateAccepted/In press - Feb 19 2018

Fingerprint

Cerebrospinal fluid
Oligoclonal Bands
Demyelinating Diseases
Cerebrospinal Fluid
Light
Immunoglobulins
Serum Albumin
Albumins
Isoelectric Focusing
Neuromyelitis Optica
Costs and Cost Analysis
Sensitivity and Specificity
Testing
Peripheral Nervous System Diseases
Serum
Autoimmunity
Multiple Sclerosis
Costs
Gels
Personnel

Keywords

  • cerebrospinal fluid
  • free light chains
  • multiple sclerosis
  • nephelometry
  • oligoclonal banding

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

CSF free light chain identification of demyelinating disease : Comparison with oligoclonal banding and other CSF indexes. / Gurtner, Kari M.; Shosha, Eslam; Bryant, Sandra C.; Andreguetto, Bruna D.; Murray, David L.; Pittock, Sean J; Willrich, Maria Alice V.

In: Unknown Journal, 19.02.2018.

Research output: Contribution to journalArticle

Gurtner, Kari M. ; Shosha, Eslam ; Bryant, Sandra C. ; Andreguetto, Bruna D. ; Murray, David L. ; Pittock, Sean J ; Willrich, Maria Alice V. / CSF free light chain identification of demyelinating disease : Comparison with oligoclonal banding and other CSF indexes. In: Unknown Journal. 2018.
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abstract = "Cerebrospinal fluid (CSF) used in immunoglobulin gamma (IgG) index testing and oligoclonal bands (OCBs) are common laboratory tests used in the diagnosis of multiple sclerosis. The measurement of CSF free light chains (FLC) could pose as an alternative to the labor-intensive isoelectric-focusing (IEF) gels used for OCBs. A total of 325 residual paired CSF and serum specimens were obtained after physician-ordered OCB IEF testing. CSF kappa (cKFLC) and lambda FLC (cLFLC), albumin and total IgG were measured. Calculations were performed based on combinations of analytes: CSF sum of kappa and lambda ([cKFLC+cLFLC]), kappa-index (K-index) ([cKFLC/sKFLC]/[CSF albumin/serum albumin]), kappa intrathecal fraction (KFLCIF) {([cKFLC/sKFLC]-[0.9358×CSF albumin/serum albumin]^[0.6687×sKFLC]/cKFLC)} and IgG-index ([CSF IgG/CSF albumin]/[serum IgG/serum albumin]). Patients were categorized as: 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) and others (n=31). cKFLC measurement used alone at a cutoff of 0.0611 mg/dL showed >90{\%} agreement to OCBs, similar or better performance than all other calculations, reducing the number of analytes and variables. When cases of demyelinating disease were reviewed, cKFLC measurements showed 86{\%} clinical sensitivity/77{\%} specificity. cKFLC alone demonstrates comparable performance to OCBs along with increased sensitivity for demyelinating diseases. Replacing OCB with cKFLC would alleviate the need for serum and CSF IgG and albumin and calculated conversions. cKFLC can overcome challenges associated with performance, interpretation, and cost of traditional OCBs, reducing costs and maintaining sensitivity and specificity supporting MS diagnosis.",
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AU - Andreguetto, Bruna D.

AU - Murray, David L.

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AU - Willrich, Maria Alice V.

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