Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A systematic review and meta-analysis

Hegen, Harald; Walde, Janette; Berek, Klaus; Arrambide, Georgina; Gnanapavan, Sharmilee; Kaplan, Batia; Khalil, Michael; Saadeh, Ruba S.; Teunissen, Charlotte E.; Tumani, Hayrettin; Villar, Luisa María; Willrich, Maria Alice V.; Zetterberg, Henrik; Deisenhammer, Florian

doi:10.1177/13524585221134213

Cited by 39 publications

(70 citation statements)

References 69 publications

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“…While specific recommendations for the implementation of κ-FLC in the diagnostic process for patients with suspected MS were developed during the meeting, the panel set out to create the whole consensus document afterwards. Furthermore, the panel decided to perform a systematic review and meta-analysis to provide a summary of the diagnostic value of κ-FLC in patients with CIS and MS and to compare its performance to OCB (published elsewhere Hegen et al 9 ).…”

Section: Methodsmentioning

confidence: 99%

“…A systematic review and meta-analysis summarized the evidence on the diagnostic accuracy of intrathecal κ-FLC synthesis to discriminate patients with CIS and MS from other neurological diseases and compared its performance to OCB. 9 …”

Section: Methodsmentioning

confidence: 99%

“…The comparison of these two parameters by bivariate mixed model – considering between-study and within-study heterogeneity and having a statistical power of 99% – clearly showed that the diagnostic accuracy of κ-FLC index and OCB are similar. 9 …”

Section: Methodsmentioning

confidence: 99%

“…However, due to the low number of studies the statistical power for these comparisons was smaller than 80% and, thus, insufficient to interpret non-statistically significant results with a small enough Type II error. For detailed analyses please refer to Hegen et al 9 …”

Section: Methodsmentioning

confidence: 99%

“…A multitude of studies have shown a high diagnostic accuracy of the κ-FLC isotype in the CSF to discriminate patients with MS from other neurological diseases; 9 and the detection of κ-FLC has considerable methodological advantages compared to the detection of OCB. 8 , 10 However, a strong consensus on the role of κ-FLC as a biomarker in MS is still lacking.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A consensus statement

et al. 2022

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Cerebrospinal fluid (CSF) analysis is of utmost importance for diagnosis and differential diagnosis of patients with suspected multiple sclerosis (MS). Evidence of intrathecal immunoglobulin G (IgG) synthesis proves the inflammatory nature of the disease, increases diagnostic certainty and substitutes for dissemination in time according to current diagnostic criteria. The gold standard to determine intrathecal IgG synthesis is the detection of CSF-restricted oligoclonal bands (OCBs). However, advances in laboratory methods brought up κ-free light chains (FLCs) as a new biomarker, which are produced in excess over intact immunoglobulins and accumulate in CSF in the case of central nervous system-derived inflammation. Overwhelming evidence showed a high diagnostic accuracy of intrathecal κ-FLC synthesis in MS with sensitivity and specificity of approximately 90% similar to OCB. κ-FLCs have advantages as its detection is fast, easy, cost-effective, reliable, rater-independent and returning quantitative results which might also improve the value of predicting MS disease activity. An international panel of experts in MS and CSF diagnostics developed a consensus of all participants. Six recommendations are given for establishing standard CSF evaluation in patients suspected of having MS. The panel recommended to include intrathecal κ-FLC synthesis in the next revision of MS diagnostic criteria as an additional tool to measure intrathecal immunoglobulin synthesis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A consensus statement

et al. 2022

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Differential Diagnosis of Suspected Multiple Sclerosis in Pediatric and Late-Onset Populations

Hua,

Solomon,

Tenembaum

et al. 2024

JAMA Neurol

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ImportanceWhile the typical onset of multiple sclerosis (MS) occurs in early adulthood, 2% to 10% of cases initially present prior to age 18 years, and approximately 5% after age 50 years. Guidance on approaches to differential diagnosis in suspected MS specific to these 2 age groups is needed.ObservationsThere are unique biological factors in children younger than 18 years and in adults older than age 50 years compared to typical adult-onset MS. These biological differences, particularly immunological and hormonal, may influence the clinical presentation of MS, resilience to neuronal injury, and differential diagnosis. While mimics of MS at the typical age at onset have been described, a comprehensive approach focused on the younger and older ends of the age spectrum has not been previously published.Conclusions and RelevanceAn international committee of MS experts in pediatric and adult MS was formed to provide consensus guidance on diagnostic approaches and key clinical and paraclinical red flags for non-MS diagnosis in children and older adults.

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Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis

et al. 2023

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Background While kappa free light chain (KFLC) index has become a useful diagnostic biomarker in multiple sclerosis (MS), its prognostic properties are less explored. B cells play a crucial role in MS pathogenesis, but the impact from increased intrathecal production of immunoglobulins and KFLC remains to be determined. Recently, it has become evident that insidious worsening is not confined to progressive MS but is also common in relapsing–remitting MS (RRMS), a feature known as progression independent of relapse activity (PIRA). Methods We retrospectively identified 131 patients with clinically isolated syndrome or early RRMS who had determined KFLC index as part of their diagnostic workup. Demographic and clinical data were extracted from the Swedish MS registry. Associations of baseline KFLC index with evidence of disease activity (EDA) and PIRA were investigated in multivariable cox proportional hazards regression models. Results KFLC index was significantly higher in PIRA (median 148.5, interquartile range [IQR] 106.9–253.5) compared with non-PIRA (78.26, IQR 28.93–186.5, p = 0.009). In a multivariable cox regression model adjusted for confounders, KFLC index emerged as an independent risk factor for PIRA (adjusted hazard ratio [aHR] 1.005, 95% confidence interval [CI] 1.002–1.008, p = 0.002). Dichotomized by the cut-off value KFLC index > 100, patients with KFLC index > 100 had an almost fourfold increase in the risk for developing PIRA. KFLC index was also predictive of evidence of disease activity during follow-up. Conclusions Our data indicate that high KFLC index at baseline is predictive of PIRA, EDA-3, and overall worse prognosis in MS.

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Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A systematic review and meta-analysis

Cited by 39 publications

References 69 publications

Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A consensus statement

Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A consensus statement

Differential Diagnosis of Suspected Multiple Sclerosis in Pediatric and Late-Onset Populations

Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis

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