TY - JOUR
T1 - CSF free light chain identification of demyelinating disease
T2 - Comparison with oligoclonal banding and other CSF indexes
AU - Gurtner, Kari M.
AU - Shosha, Eslam
AU - Bryant, Sandra C.
AU - Andreguetto, Bruna D.
AU - Murray, David L.
AU - Pittock, Sean J.
AU - Willrich, Maria Alice V.
N1 - Funding Information:
Acknowledgments: The study was funded, in part, by the Department of Laboratory Medicine and Pathology at Mayo Clinic. Reagents for measurement of kappa free light chains were provided by The Binding Site (Birmingham, UK). This project was supported by Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS). Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Employment or leadership: None declared. Honorarium: None declared. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Publisher Copyright:
© 2018 2018 Walter de Gruyter GmbH, Berlin/Boston.
PY - 2018/6/27
Y1 - 2018/6/27
N2 - 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 (KFLC IF ) {([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.
AB - 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 (KFLC IF ) {([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.
KW - cerebrospinal fluid
KW - free light chains
KW - multiple sclerosis
KW - nephelometry
KW - oligoclonal banding
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U2 - 10.1515/cclm-2017-0901
DO - 10.1515/cclm-2017-0901
M3 - Article
C2 - 29455184
AN - SCOPUS:85042728754
SN - 1434-6621
VL - 56
SP - 1071
EP - 1080
JO - Zeitschrift fur klinische Chemie und klinische Biochemie
JF - Zeitschrift fur klinische Chemie und klinische Biochemie
IS - 7
ER -