Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band‐negative patients with suspected multiple sclerosis

A 49-year-old woman sought care for a 9-month history of gait difficulty. She was dragging her right foot when walking and could not walk more than 3 blocks because of right leg weakness. Physical examination showed right-sided weakness of hip flexion and foot dorsiflexion and symmetrical hyperreflexia at the knees and ankles. Magnetic resonance imaging of the brain showed multiple foci of T2 hyperintensity throughout the white matter in both cerebral and cerebellar hemispheres, predominantly in a periventricular distribution. Several small enhancing lesions and mild generalized cerebral volume loss were seen. The appearance and distribution were consistent with a demyelinating process such as multiple sclerosis. Magnetic resonance imaging of the cervical and thoracic spine showed multiple small T2 hyperintensities, including 1 enhancing lesion in the cervical spinal cord. Oligoclonal bands were positive, with 11 unique bands in the cerebrospinal fluid. The concentration of cerebrospinal fluid kappa free light chains was increased, at 0.314 mg/dL. The patient was diagnosed with relapsing-remitting multiple sclerosis. A 5-day course of intravenous corticosteroids was started, after which she noted clinical improvement. At her last follow-up 2 years after initial evaluation, the patient has been stable with no new clinical multiple sclerosis episodes and stable magnetic resonance imaging disease burden with no new lesions. The diagnosis of multiple sclerosis incorporates clinical, imaging, and laboratory evidence. The 2017 revised McDonald criteria state that a finding of cerebrospinal fluid -specific oligoclonal bands can replace the criterion for dissemination in time to make a diagnosis of definitive multiple sclerosis. The standard test for oligoclonal bands is performed using isoelectric focusing electrophoresis and takes more than 3 hours to complete. The case patient had 11 unique cerebrospinal fluid bands. The number of bands is not correlated with disease severity or prognosis.

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Application of κ free light chains in cerebrospinal fluid as a biomarker in multiple sclerosis diagnosis: development of a diagnosis algorithm

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0285 ◽

2018 ◽

Vol 56 (4) ◽

pp. 609-613 ◽

Cited By ~ 13

Author(s):

Estefania Valencia-Vera ◽

Ana Martinez-Escribano Garcia-Ripoll ◽

Alfredo Enguix ◽

Carmen Abalos-Garcia ◽

Maria Jesus Segovia-Cuevas

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

High Sensitivity ◽

Demyelinating Diseases ◽

Oligoclonal Bands ◽

Light Chains ◽

Moderate Increase ◽

Free Light Chains ◽

Cross Sectional ◽

Significant Difference

Abstract Background: The determination of κ free light chains (KFLC) in cerebrospinal fluid (CSF) by nephelometry is a feasible alternative to immunoglobulin G oligoclonal bands (OCB) in the evaluation of intrathecal synthesis of immunoglobulin in multiple sclerosis (MS) and other demyelinating diseases. The aim of this study was to assess the diagnostic value of KFLC and its inclusion in a procedure algorithm along with OCB interpretation. Methods: A cross-sectional study, which included 123 patients with a CSF OCB request, was carried out. Isoelectric focusing followed by immunofixation was used to detect OCB, and nephelometry was used to analyze KFLC. The KFLC index was calculated using CSF/serum quotient of KFLC and albumin. The KFLC index was compared with MS diagnosis to find the optimal cutoff. It was obtained from the receiver operating characteristic (ROC) curves and the Youden method. Results: The CSF KFLC median was 1.66 mg/L in the MS group, whereas in other central nervous system diseases, KFLC showed generally no or only moderate increase in CSF (median 0.10 mg/L). KFLC index showed a significant difference between groups. ROC analysis for CSF KFLC concentration, and KFLC indexes were 91.88% and 93.94%, respectively. The best cutoff for the KFLC index was 2.91 for MS diagnosis (sensitivity: 83.78%; specificity: 85.88%). The proposed algorithm showed high sensitivity (89.19%) and specificity (84.71%). Conclusions: KFLC determination is rapid and automatized, but it has no higher sensitivity and specificity than OCB in MS diagnosis. Nevertheless, when used in screening, it could reduce the number of manual OCB tests.

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Association of cerebrospinal fluid kappa free light chains with the intrathecal polyspecific antiviral immune response in multiple sclerosis

Clinica Chimica Acta ◽

10.1016/j.cca.2019.08.016 ◽

2019 ◽

Vol 498 ◽

pp. 148-153 ◽

Cited By ~ 3

Author(s):

André Huss ◽

Fatemeh Mojib-Yezdani ◽

Franziska Bachhuber ◽

Tanja Fangerau ◽

Jan Lewerenz ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune Response ◽

Cerebrospinal Fluid ◽

Light Chains ◽

Free Light Chains ◽

Antiviral Immune Response

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Concentrations of immunoglobulin free light chains in cerebrospinal fluid predict increased level of brain atrophy in multiple sclerosis

Immunologic Research ◽

10.1007/s12026-018-9058-8 ◽

2018 ◽

Vol 66 (6) ◽

pp. 761-767 ◽

Cited By ~ 2

Author(s):

Vladimir Nazarov ◽

Gleb Makshakov ◽

Ivan Kalinin ◽

Sergey Lapin ◽

Elena Surkova ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Brain Atrophy ◽

Light Chains ◽

Free Light Chains

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Cerebrospinal fluid free light chains determination in oligoclonal bands negative patients with suspected multiple sclerosis

Clinica Chimica Acta ◽

10.1016/j.cca.2019.03.1291 ◽

2019 ◽

Vol 493 ◽

pp. S616-S617

Author(s):

D. Ferraro ◽

P. Natali ◽

A. Trovati ◽

R. Bedin ◽

F. Vitetta ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Oligoclonal Bands ◽

Light Chains ◽

Free Light Chains

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Cerebrospinal fluid free light chains compared to oligoclonal bands as biomarkers in multiple sclerosis

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2019.577108 ◽

2020 ◽

Vol 339 ◽

pp. 577108 ◽

Cited By ~ 4

Author(s):

Lorenzo Gaetani ◽

Marinella Di Carlo ◽

Giovanni Brachelente ◽

Federico Valletta ◽

Paolo Eusebi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Oligoclonal Bands ◽

Light Chains ◽

Free Light Chains

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The Persisting Significance of Oligoclonal Bands in the Dawning Era of Kappa Free Light Chains for the Diagnosis of Multiple Sclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms19123796 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3796 ◽

Cited By ~ 12

Author(s):

Philipp Schwenkenbecher ◽

Franz Konen ◽

Ulrich Wurster ◽

Konstantin Jendretzky ◽

Stefan Gingele ◽

...

Keyword(s):

Multiple Sclerosis ◽

Light Chain ◽

Clinically Isolated Syndrome ◽

Free Light Chain ◽

Oligoclonal Bands ◽

Light Chains ◽

Oligoclonal Band ◽

Free Light Chains ◽

Mcdonald Criteria

The latest revision of the McDonald criteria of 2017 considers the evidence of an intrathecal immunoglobulin (IgG) synthesis as a diagnostic criterion for dissemination in time in multiple sclerosis. While the detection of oligoclonal bands is considered as the gold standard, determination of kappa free light chains might be a promising tool as a less technically demanding and cost saving method. However, data on the direct comparison between kappa free light chains and oligoclonal bands are limited and no study to date has used the highly sensitive method of polyacrylamide gels with consecutive silver staining for the demonstration of oligoclonal bands. Furthermore, the impact of the revised McDonald criteria of 2017 on the role of kappa free light chains as a biomarker has not been investigated. Nephelometry was used to determine kappa free light chains in cerebrospinal fluid (CSF) and serum from 149 patients with their first demyelinating event between 2010 and 2015. Clinical data, kappa free light chains, and oligoclonal band status were compared at the time of initial diagnosis and after follow-up to identify converters from clinically isolated syndrome to multiple sclerosis. An elevated kappa free light chain index (>5.9) was found in 79/83 patients (95%) with multiple sclerosis diagnosed at baseline, slightly less frequent than oligoclonal bands (98.8%). 18/25 (72%) patients who converted from clinically isolated syndrome to multiple sclerosis showed an elevated kappa free light chain index compared to 20/25 (80%) patients with positive oligoclonal bands. In patients with stable clinically isolated syndrome 7/41 (17%) displayed an elevated kappa free light chain index against 11/41 (27%) oligoclonal band positive patients. Only two patients with stable clinically isolated syndrome showed an elevated kappa free light chain index but were oligoclonal bands negative. In conclusion, determination of the kappa free light chain index is a promising diagnostic approach to assess intrathecal immunoglobulin synthesis in multiple sclerosis. Nevertheless, oligoclonal bands are highly prevalent in multiple sclerosis and can detect an intrathecal synthesis of IgG even when the kappa free light chain index is below the threshold. We consider sequential use of both methods as reasonable.

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