Free Kappa light chains in neuroinflammatory disorders: Complement rather than substitute?

Bayart, Jean‐Louis; Muls, Nathalie; Pesch, Vincent Van

doi:10.1111/ane.12969

Cited by 17 publications

(19 citation statements)

References 27 publications

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“…CSF and blood samples were collected at the Cliniques Universitaires Saint-Luc (Brussels) between March 2005 and March 2018, processed according to international guidelines within 1 hour before storage at −80°C until miRNA extraction. 6,7 PBMCs paired with serum were processed as previously described. 8 The study was conducted stepwise (figure 1).…”

Section: Patientsmentioning

confidence: 99%

“…ROC curve analysis was the strongest for miR-150-5p, with a sensitivity and specificity of 80% and 81%, respectively, an even stronger result than previously shown 19 and comparable to ROC curves of kappa free light chains for MS diagnosis. 7 The set of miRNAs (miR-20a-5p, -145-5p, -214-3p, -27a-3p, -27b-3p, -24-3p, and -29c-3p) whose expression was modified according to disease activity could be sufficient to segregate patients with relapsing MS from patients with remitting MS. Further studies, in larger independent cohorts, should investigate whether these miRNAs could serve as biomarkers of disease activity. MiRNA profile in the serum and PBMCs of patients with MS Five miRNAs were downregulated in the serum of both relapsing and remitting MS (miR-15a-3p, -24-3p, -126-3p, -146a-3p, and -181c-5p), whereas miR-214-3p was downregulated in the serum of relapsing MS only.…”

Section: Csf-predominant Mirna Dysregulation and Mirna Species Newly mentioning

confidence: 99%

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CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders

Perdaens

Dang

D’Auria

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo perform a comprehensive multicompartment analysis of microRNA (miRNA) expression in multiple sclerosis (MS) linked to disease activity and compared with other neuroinflammatory diseases through a retrospective cross-sectional study.MethodsOne hundred twenty-seven miRNAs were measured by PCR arrays on pooled CSF, serum, and peripheral blood mononuclear cell (PBMC) samples of 10 patients with relapsing MS and 10 controls. Sixty-four miRNAs were then measured by quantitative PCR on individual CSF samples of patients with relapsing or remitting MS and controls (n = 68). Fifty-seven miRNAs were analyzed in the CSF from a second cohort (n = 75), including patients with MS, neuroinfectious, or neuroinflammatory diseases and controls. MiRNAs significantly dysregulated in the CSF were analyzed on individual serum/PBMC samples (n = 59/48) of patients with relapsing or remitting MS and controls. Post hoc analysis consisted of principal component analysis (PCA), gene set, and pathway enrichment analysis.ResultsTwenty-one miRNAs were differentially expressed, mainly upregulated in the CSF during MS relapses. Relapsing MS and neuroinfectious/inflammatory diseases exhibited a partially overlapping CSF miRNA expression profile. Besides confirming the association of miR-146a-5p/150-5p/155-5p with MS, 7 miRNAs uncharacterized for MS emerged (miR-15a-3p/124-5p/149-3p/29c-3p/33a-3p/34c-5p/297). PCA showed that distinct miRNA sets segregated MS from controls and relapse from remission. In silico analysis predicted the involvement of these miRNAs in cell cycle, immunoregulation, and neurogenesis, but also revealed that the signaling pathway pattern of remitting MS is more akin to controls rather than patients with relapsing MS.ConclusionsThis study highlights the CSF-predominant dysregulation of miRNAs in MS by identifying a signature of disease activity and intrathecal inflammation among neuroinflammatory disorders.

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Section: Patientsmentioning

confidence: 99%

Section: Csf-predominant Mirna Dysregulation and Mirna Species Newly mentioning

confidence: 99%

CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders

Perdaens

Dang

D’Auria

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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“…Kvantifikace fLC pomocí rozdílných reagencií/ přístrojů nemusí poskytovat srovnatelné hodnoty umožňující univerzální použití jediné cut-off hodnoty pro výpočet intratékální syntézy fLC. Diskrepantní výsledky mezi kvantitativními a kvalitativními testy pro fKLC byly publikovány v recentní studii [33]. Přestože se ukázalo, že detekce o-fLC může být nepatrně senzitivnějším testem než o-IgG pro průkaz intratékálního zánětu, může být také méně specifická pro RS než o-IgG [5][6][7][8].…”

Section: Srovnání S Výpočty Intratékální Syntézy Igg a Flcunclassified

“…Přestože se ukázalo, že detekce o-fLC může být nepatrně senzitivnějším testem než o-IgG pro průkaz intratékálního zánětu, může být také méně specifická pro RS než o-IgG [5][6][7][8]. Proto souhlasíme s Bayartem et al [33], že testy fLC by měly být používány spíše jako doplněk než jako náhrada za analýzu o-IgG, jejíž klíčové postavení je zakotveno i v doporučeních českých odborných společností [34,35].…”

Section: Srovnání S Výpočty Intratékální Syntézy Igg a Flcunclassified

Oligoclonal IgG and free light chains – comparison between agarose and polyacrylamide isoelectric focusing

Zeman¹,

Kušnierová²,

Hradílek³

et al. 2019

Cask Slov Neurol N

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Oligoclonal IgG and free light chains-comparison between agarose and polyacrylamide isoelectric focusing Souhrn Cíl: Porovnání izoelektrické fokusace v agarosovém a polyakrylamidovém gelu pro detekci oligoklonálních pásů imunoglobulinu G (o-IgG) a oligoklonálních volných lehkých řetězců (oligoclonal free light chains; o-fLC). Soubor a metody: Detekce oligoklonálních pásů byla provedena v sérii 106 (o-IgG), resp. 48 (o-fLC) konsekutivních párových vzorků likvorů a sér. Pro srovnání obou metod a shody mezi hodnotícími byla použita statistika kappa. Výsledky: Při rozdělení nálezů na negativní a pozitivní byly rozdílně hodnoceny jen tři vzorky (2,8 %) pro o-IgG, tři vzorky (6,2 %) pro o-fLC kappa a jediný vzorek (2,1 %) pro o-fLC lambda. V těchto diskrepantních případech byl pozorován rozdíl nejvýše tří pásů. Shoda mezi hodnotícími pro o-fLC byla velmi dobrá (κ = 0,906-1,000). Závěry: Přestože polyakrylamidový gel může být teoreticky výhodnější vzhledem k menší velikosti pórů a lepšímu rozlišení, naše výsledky byly jak pro o-IgG, tak pro o-fLC velmi podobné jako při separaci v agarózovém gelu. Obě metody hodnotíme jako dobře použitelné a rozdíly mezi nimi byly omezeny na hraničně pozitivní případy.

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“…The gold standard for CSF analysis is isoelectric focusing (IEF) to detect CSF oligoclonal bands (OB) of immunoglobulin (Ig) G. Historically, intrathecal synthesis of IgG has been detected as an elevated immunoglobulin G (IgG) or Link index, calculated as the ratio of CSF/serum IgG to CSF/serum albumin [4]. Recently, measures of free light chains (FLC) by nephelometry have been proposed as an alternative method to IgG index and OB detection by IEF [5]. Despite the role of lambda (λ) FLC remains controversial, there is robust evidence for kappa (K) FLC [6,7].…”

Section: Introductionmentioning

confidence: 99%

K Index is a Reliable Marker of Intrathecal Synthesis, and an Alternative to IgG Index in Multiple Sclerosis Diagnostic Work-Up

Crespi

Vecchio

Serino

et al. 2019

JCM

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The K free light chain (K) index has been suggested as a reliable marker of intrathecal synthesis,despite the 2017 McDonald criteria for multiple sclerosis (MS) suggesting to “interpret with caution positiveimmunoglobulin G (IgG) index when testing for oligoclonal bands (OB) is negative or not performed”. Theaim of this study was to compare the performance of K and IgG indexes for MS diagnosis and OB detectionin a cohort of Italian patients. We enrolled 385 patients (127 MS, 258 non-MS) who had cerebrospinal fluid(CSF) analysis, including isoelectric focusing (IEF), to detect OB in the diagnostic work-up. Albumin, IgGand free light chains were measured by nephelometry and used to calculate IgG and K indexes. Althoughthe two markers were highly related (r = 0.75, r2 = 0.55, p < 0.0001), the K index showed greater sensitivity andnegative predictive value (versus the IgG index) for OB detection (97% versus 48% and 97% versus 71%) andMS diagnosis (96% versus 50% and 98% versus 78%). These results support K index (and not IgG index) as afirst-line marker for MS, followed by IEF, according to a sequential testing approach in CSF analysis.

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Free Kappa light chains in neuroinflammatory disorders: Complement rather than substitute?

Abstract: Our results demonstrate that the κFLC index does not discriminate MS from other IND patients, but is a reliable technique to detect intrathecal inflammation. However, κFLC quantification should probably be considered as a complementary method, rather than a substitute, to OCB detection.

Cited by 17 publications

References 27 publications

CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders

CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders

Oligoclonal IgG and free light chains – comparison between agarose and polyacrylamide isoelectric focusing

K Index is a Reliable Marker of Intrathecal Synthesis, and an Alternative to IgG Index in Multiple Sclerosis Diagnostic Work-Up

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