scholarly journals Intrathecal kappa free light chains as markers for multiple sclerosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
D. Vecchio ◽  
G. Bellomo ◽  
R. Serino ◽  
E. Virgilio ◽  
M. Lamonaca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Light Chain ◽  
Neurological Diseases ◽  
High Sensitivity ◽  
Free Light Chain ◽  
Prognostic Impact ◽  
Free Light Chains ◽  
Igg Synthesis ◽  
Intrathecal Igg Synthesis ◽  
Reliable Marker

AbstractCerebrospinal fluid (CSF) kappa free light chain (KFLC) index has been described as a reliable marker of intrathecal IgG synthesis to diagnose multiple sclerosis (MS). Our aims were: (1) to compare the efficiency of KFLC through different interpretation approaches in diagnosing MS. (2) to evaluate the prognostic value of KFLC in radiologically and clinically isolated syndromes (RIS-CIS). We enrolled 133 MS patients and 240 with other neurological diseases (93 inflammatory including 18 RIS-CIS, 147 non-inflammatory). Albumin, lambda free light chain (LFLC) and KFLC were measured in the CSF and serum by nephelometry. We included two groups of markers: (a) corrected for blood-CSF barrier permeability: immunoglobulin G (IgG), KFLC and LFLC indexes. (b) CSF ratios (not including albumin and serum-correction): CSF KFLC/LFLC, CSF KFLC/IgG, CSF LFLC/IgG. KFLC were significantly higher in MS patients compared to those with other diseases (both inflammatory or not). KFLC index and CSF KFLC/IgG ratio showed high sensitivity (93% and 86.5%) and moderate specificity (85% and 88%) in diagnosing MS. RIS-CIS patients who converted to MS showed greater KFLC index and CSF KFLC/IgG. Despite OB are confirmed to be the gold-standard to detect intrathecal IgG synthesis, the KFLC confirmed their accuracy in MS diagnosis. A “kappa-oriented” response characterizes MS and has a prognostic impact in the RIS-CIS population.

scholarly journals Recommendations for Use of Free Light Chain Assay in Monoclonal Gammopathies

2010 ◽  
Vol 29 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Vesna Radović
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
High Sensitivity ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Bone Marrow Biopsies ◽  
Monoclonal Gammopathies ◽  
Plasma Cell Disorders

Recommendations for Use of Free Light Chain Assay in Monoclonal GammopathiesThe serum immunoglobulin free light chain assay measures levels of free κ and λ immunoglobulin light chains. There are three major indications for the free light chain assay in the evaluation and management of multiple myeloma and related plasma cell disorders. In the context of screening, the serum free light chain assay in combination with serum protein electrophoresis and immunofixation yields high sensitivity, and negates the need for 24-hour urine studies for diagnoses other than light chain amyloidosis. Second, the baseline free light chains measurement is of major prognostic value in virtually every plasma cell disorder. Third, the free light chain assay allows for quantitative monitoring of patients with oligosecretory plasma cell disorders, including AL, oligosecretory myeloma, and nearly twothirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial free light chains measurements outperform protein electrophoresis and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial free light chains measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using free light chain assay in place of 24-hour urine electrophoresis for monitoring or for serial measurements in plasma cell disorders with measurable disease by serum or urine electrophoresis.

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

2018 ◽  
Vol 19 (12) ◽  
pp. 3796 ◽  
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.

scholarly journals Prognostic impact of rapid reduction of involved free light chains in multiple myeloma patients under first-line treatment with Bendamustine, Prednisone, and Bortezomib (BPV)

2021 ◽  
Author(s):  
Tanja Holzhey ◽  
Wolfram Pönisch ◽  
Song-Yau Wang ◽  
Madlen Holzvogt ◽  
Bruno Holzvogt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Median Number ◽  
Free Light Chain ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Free Light Chains ◽  
Rapid Reduction ◽  
Prognostic Importance ◽  
Abnormal Ratio

Abstract Introduction Light chain involvement is observed in almost every patient (pt) with newly diagnosed multiple myeloma (MM). Owing to a relatively short half-life, rapid reduction in the involved free light chain (iFLC) is of potential prognostic value. Methods This retrospective analysis included 92 pts with newly diagnosed MM treated with bendamustine, prednisone, and bortezomib (BPV). Results After a median number of two (range 1–5) BPV cycles, the majority of pts (n = 86; 93%) responded with either sCR (n = 21), CR (n = 1), nCR (n = 25), VGPR (n = 20), or PR (n = 19). PFS and OS at 48 months were 39% and 67%, respectively. At baseline, 79 out of 92 pts (86%) had iFLC levels above the upper standard level and an abnormal ratio of involved to uninvolved free light chain ≥ 8. In a subgroup analysis of these pts, we evaluated the prognostic importance of an early reduction of the iFLC during the first two BPV cycles. A reduction ≥ 50% of the iFLC on day 8 of the first cycle was observed in 31 of 69 pts. These pts had a significantly better median PFS of 49 months as compared to 20 months in 38 pts with a lower iFLC reduction (p = 0.002). In contrast, OS did not differ significantly with a 48 months survival of 77% vs 69% (p > 0.05). Conclusion These results indicate that a rapid decrease in the iFLC on day 8 is an early prognostic marker for newly diagnosed MM pts undergoing BPV treatment.

Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: A multicenter study

2015 ◽  
Vol 22 (4) ◽  
pp. 502-510 ◽  
Author(s):  
Stefan Presslauer ◽  
Dejan Milosavljevic ◽  
Wolfgang Huebl ◽  
Fahmy Aboulenein-Djamshidian ◽  
Walter Krugluger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Multicenter Study ◽  
Neurological Diseases ◽  
Diagnostic Value ◽  
Clinically Isolated Syndrome ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Diagnostic Biomarker ◽  
Free Light Chains ◽  
Igg Synthesis

Background: Kappa free light chains (KFLCs) have been proposed as a diagnostic biomarker in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS). Objective: The objective of this paper is to validate the diagnostic accuracy of intrathecal KFLC synthesis in a multicenter study. Methods: KFLCs were measured by nephelometry under blinded conditions in cerebrospinal fluid (CSF) and serum sample pairs of patients with CIS ( n = 60), MS ( n = 60) and other neurological diseases ( n = 60) from four different MS centers. The upper normal limit for intrathecal KFLC concentrations depending on blood-CSF barrier function was previously calculated in a cohort of 420 control patients. Results: Diagnostic sensitivity of intrathecal KFLC synthesis, IgG synthesis according to Reiber, IgG index and oligoclonal bands (OCBs) was 95%, 72%, 73% and 93% in patients with MS and 82%, 47%, 43% and 72% in patients with CIS. Specificity of intrathecal KFLC synthesis was 95% and 98% for all other measures. Conclusion: These findings further support the diagnostic value of intrathecal KFLC synthesis in CIS and MS patients and demonstrate a valid, easier and rater-independent alternative to OCB detection.

Lambda monoclonal free light chain abnormalities detected by a serum immunofixation electrophoresis assay are underrepresented by quantitative serum free light chain results

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S13-S14
Author(s):  
Rebecca Treger ◽  
Kathleen Hutchinson ◽  
Andrew Bryan ◽  
Chihiro Morishima
Keyword(s):  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Sample Population ◽  
Free Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Immunofixation Electrophoresis ◽  
High Concordance ◽  
Polyclonal Antisera

Abstract Protein and immunofixation (IFIX) electrophoresis are used to diagnose and monitor monoclonal gammopathies. While IFIX detects clonal production of intact immunoglobulins and free light chains (FLC), the latter can also be quantified using a serum free light chain (SFLC) assay, in which polyclonal antisera detects epitopes specific for free kappa (KFLC) or lambda light chains (LFLC). An abnormal KFLC: LFLC ratio (KLR) serves as a surrogate for clonality. While the SFLC assay is highly sensitive, normal LFLC (<2.63mg/dL) and KLR results (>0.26 & <1.65) were found in samples with distinct lambda monoclonal free light chains visualized by IFIX (X-LMFLC). To investigate this discordance, contemporaneous SFLC or KLR values were evaluated for their ability to accurately classify monoclonal FLCs identified by IFIX. We performed a retrospective analysis of serum and urine IFIX (Sebia Hydrasys) and SFLC (Freelite®, Binding Site) results from our institution between July 2010 through December 2020, using R 4.0.2 and Tidyverse packages. From among 9,594 encounters in which a single monoclonal component was initially identified by IFIX, 157 X-LMFLC and 131 X-KMFLC samples were analyzed. Elevated LFLC with normal KFLC was identified in 105/157 X-LMFLC samples (67%), while both LFLC and KFLC were elevated in 42/157 samples (27%). Concordance between X-KMFLC and KFLC was markedly higher, where 122/131 samples (93%) displayed elevated kappa FLC (>1.94mg/dL) with normal LFLC, and only 7/131 X-KMFLC samples (5%) possessed both elevated KFLC and LFLC. The use of KLR to identify pathogenic monoclonal free light chains improved lambda concordance to 85%; however, 19/157 (12%) of X-LMFLC samples still exhibited normal KLR. High concordance of 98% was again observed for X-KMFLC with abnormal KLR. When samples were segregated according to normal or impaired renal function (eGFR > or ≤60mL/min/1.73m², respectively), this disparate identification of X-LMFLC and X-KMFLC by the SFLC assay persisted, suggesting that renal dysfunction (as measured by eGFR) does not underlie this phenomenon. Lastly, we corroborated the above findings in a larger sample population by examining patients with urine Bence Jones FLC identified by IFIX who had free or intact monoclonal components in serum (N=724), grouped by lambda or kappa light chain involvement. The cause(s) of the discrepant performance by the Freelite® SFLC assay, relative to the Sebia Hydrasys IFIX assay, for identifying lambda FLC components is currently unclear. Possible contributory factors include assay reference range cutoffs, other patient disease parameters, and differences in assay-specific polyclonal antisera. Future analyses of these factors will help to further characterize SFLC assay performance and elucidate how interpretation of composite serum FLC test results can be improved to better guide patient management.

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.

Blood-CSF barrier permselectivity and measurement of intrathecal IgG synthesis in multiple sclerosis

1984 ◽  
pp. 441-447
Author(s):  
P. Livrea ◽  
I. L. Simone ◽  
M. Trojano ◽  
G. B. Zimatore ◽  
R. Pisicchio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Igg Synthesis ◽  
Intrathecal Igg Synthesis
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