Kappa free light chains in cerebrospinal fluid to identify patients with oligoclonal bands

2018 ◽  
Vol 25 (9) ◽  
pp. 1134-1139 ◽  
Author(s):  
M. Süße ◽  
M. Hannich ◽  
A. Petersmann ◽  
S. Zylla ◽  
M. Pietzner ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Free Light Chains

New-Onset Gait Difficulty With Kappa Free Light Chains in Cerebrospinal Fluid

2021 ◽  
pp. 42-43
Author(s):  
Maria Alice V. Willrich ◽  
Ruba S. Saadeh
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Resonance Imaging ◽  
Free Light Chains ◽  
Mcdonald Criteria ◽  
T2 Hyperintensity

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.

scholarly journals Kappa Free Light Chains in Cerebrospinal Fluid as Markers of Intrathecal Immunoglobulin Synthesis

2004 ◽  
Vol 50 (10) ◽  
pp. 1809-1813 ◽  
Author(s):  
Christian Fischer ◽  
Borros Arneth ◽  
Jürgen Koehler ◽  
Johannes Lotz ◽  
Karl J Lackner
Keyword(s):  
Cerebrospinal Fluid ◽  
Diagnostic Accuracy ◽  
Barrier Function ◽  
High Specificity ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Free Light Chains ◽  
Blood Contamination ◽  
Immunoglobulin Synthesis ◽  
Specificity And Sensitivity

Abstract Background: Intrathecal immunoglobulin synthesis is observed in several inflammatory disorders of the central nervous system, but its detection by current laboratory tests is either tedious or relatively insensitive. We assessed the diagnostic accuracy of an assay for κ free light chains (κFLC) in cerebrospinal fluid (CSF) and serum, and compared it with traditional tests for intrathecal immunoglobulin synthesis. Methods: κFLCs were measured by nephelometry in CSF/serum pairs from 112 patients. Samples were excluded if blood contamination of CSF as a result of traumatic lumbar puncture (n = 12) or monoclonal bands in both CSF and serum (n = 5) were present. The remaining sample pairs were grouped according to the presence (n = 71) or absence (n = 24) of oligoclonal bands. Data were analyzed as κFLC concentrations in CSF, as κFLC CSF/serum ratios, and by use of the quotient diagram described previously for immunoglobulins. Results: Both κFLC concentrations in CSF and the κFLC CSF/serum ratio identified patients with oligoclonal bands with high specificity and sensitivity. The areas under the ROC curves were 0.991 (95% confidence interval, 0.944–0.998) and 0.978 (0.924–0.996), respectively. Exclusion of patients with impaired blood–CSF barrier function further improved diagnostic accuracy. To account for patients with impaired blood–CSF barrier function, data were also analyzed in a quotient diagram. Only two patients without detectable oligoclonal bands would have been misclassified by this approach. Conclusions: Our data indicate that the nephelometric assay for κFLCs in CSF reliably detects intrathecal immunoglobulin synthesis. This automated and quantitative method could simplify the diagnostic procedure for CSF analysis in the routine laboratory.

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

2018 ◽  
Vol 56 (4) ◽  
pp. 609-613 ◽  
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.

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

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

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

2020 ◽  
Vol 339 ◽  
pp. 577108 ◽  
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

Free light chains in the cerebrospinal fluid. Comparison of different methods to determine intrathecal synthesis

2019 ◽  
Vol 57 (10) ◽  
pp. 1574-1586
Author(s):  
Harald Hegen ◽  
Janette Walde ◽  
Dejan Milosavljevic ◽  
Fahmy Aboulenein-Djamshidian ◽  
Makbule Senel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Diagnostic Performance ◽  
Neurological Diseases ◽  
Diagnostic Value ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Control Group ◽  
Free Light Chains ◽  
Diagnostic Biomarkers ◽  
Reference Limit

Abstract Background Free light chains (FLC) have been proposed as diagnostic biomarkers in the cerebrospinal fluid (CSF) of patients with inflammatory central nervous system (CNS) diseases. However, which method to use for determining an intrathecal FLC synthesis has not yet been clarified. The objective of this study was to compare the diagnostic performance of CSF FLC concentration, FLC quotient (QFLC), FLC index and FLC intrathecal fraction (FLCIF). Methods κ- and λ-FLC were measured by nephelometry under blinded conditions in CSF and serum sample pairs of patients with clinically isolated syndrome (CIS; n = 60), multiple sclerosis (MS; n = 60) and other neurological diseases (n = 60) from four different MS centers. QFLC was calculated as the ratio of CSF/serum FLC concentration, the FLC index as QFLC/albumin quotient and the percentage FLCIF by comparing QFLC to a previously empirically determined, albumin quotient-dependent reference limit. Results CSF FLC concentration, QFLC, FLC index and FLCIF of both the κ- and λ-isotype were significantly higher in patients with CIS and MS than in the control group, as well as in oligoclonal bands (OCB) positive than in OCB negative patients. Each parameter was able to identify MS/CIS patients and OCB positivity, however, diagnostic performance determined by receiver operating characteristic (ROC) analyses differed and revealed superiority of FLC index and FLCIF. Conclusions These findings support the diagnostic value of FLC measures that correct for serum FLC levels and albumin quotient, i.e. blood-CSF barrier function.

Free light chains in cerebrospinal fluid of multiple sclerosis patients negative for IgG oligoclonal bands

2019 ◽  
Vol 496 ◽  
pp. 117-120 ◽  
Author(s):  
Sara Altinier ◽  
Marco Puthenparampil ◽  
Martina Zaninotto ◽  
Elisabetta Toffanin ◽  
Susanna Ruggero ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Free Light Chains ◽  
Multiple Sclerosis Patients

The contribute of cerebrospinal fluid free light-chain assay in the diagnosis of multiple sclerosis and other neurological diseases in an Italian multicenter study

2021 ◽  
pp. 135245852110641
Author(s):  
Gaetano Bernardi ◽  
Tiziana Biagioli ◽  
Paola Malpassi ◽  
Teresa De Michele ◽  
Domizia Vecchio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disorders ◽  
Operating Characteristic ◽  
Neurological Diseases ◽  
Characteristic Curve ◽  
Oligoclonal Bands ◽  
Free Light Chains ◽  
Complementary Information ◽  
Combined Use

Background: Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus. Objective: To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases. Methods: A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite. Results: A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups ( p < 0.0001). The kFLC index ⩾ 6.4 is comparable to OCB for MS diagnosis (area under the receiver operating characteristic curve (AUC) = 0.876; sensitivity 83.6% vs 84.2%; specificity 88.5% vs 90.6%). λFLC index ⩾ 5 showed an AUC of 0.616, sensitivity of 33.3% and specificity of 90.6%. In all, 12/27 (44.4%) MS patients with negative OCB had kFLC index ⩾ 6.4. Interestingly, 37.5% of 24 patients with a single CSF IgG band showed high kFLC index and 12.5% positive λFLC index. Conclusion: Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.

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