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Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

ABSTRACT: OBJECTIVE:To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS:We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS:The cut-off for the KFLC index was 6.6 (95% confidence interval (CI)?=?5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI?=?4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI?=?0.85-0.90) was higher than OCB (0.82; 95%CI?=?0.79-0.85; p?

SUBMITTER: Leurs CE

PROVIDER: S-EPMC7350201 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

Leurs C E CE Twaalfhoven Ham H Lissenberg-Witte B I BI van Pesch V V Dujmovic I I Drulovic J J Castellazzi M M Bellini T T Pugliatti M M Kuhle J J Villar L M LM Alvarez-Cermeño J C JC Alvarez-Lafuente R R Hegen H H Deisenhammer F F Walchhofer L M LM Thouvenot E E Comabella M M Montalban X X Vécsei L L Rajda C C Galimberti D D Scarpini E E Altintas A A Rejdak K K Frederiksen J L JL Pihl-Jensen G G Jensen Peh P Khalil M M Voortman M M MM Fazekas F F Saiz A A La Puma D D Vercammen M M Vanopdenbosch L L Uitdehaag Bmj B Killestein J J Bridel C C Teunissen C C

Multiple sclerosis (Houndmills, Basingstoke, England) 20190508 8

<h4>Objective</h4>To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS).<h4>Methods</h4>We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off ...[more]

PMID: 31066634

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Project description:Intrathecal synthesis of free light chains kappa (FLCK) is increasingly recognized as a marker of inflammatory CNS pathologies. Here, we tested the performance of FLCK in differentiating autoimmune encephalitis (AIE) from non-inflammatory etiologies in subacute onset neuropsychiatric syndromes. Patients undergoing diagnostic work-up for suspected autoimmune encephalitis at our department between 2015 and 2020 were retrospectively assessed for definitive diagnosis, available CSF and blood samples, as well as complete clinical records. Intrathecal FLCK was measured along with established CSF markers of CNS inflammation. The study cohort consisted of 19 patients with antibody-mediated AIE (AIE+), 18 patients with suspected AIE but without detectable autoantibodies (AIE-), 10 patients with infectious (viral) encephalitis (INE), and 15 patients with degenerative encephalopathies (DGE). 25 age- and sex-matched patients with non-inflammatory neurological diseases (NIND) were used as a control group. All AIE+ patients exhibited intrathecal synthesis of FLCK compared to only 39% of AIE- patients and 81% of patients in the INE group. No intrathecal synthesis of FLCK was found in DGE and NIND patients. While intrathecal FLCK was equally specific for an inflammatory etiology as oligoclonal bands (OCB) in the cerebrospinal fluid (CSF), the sensitivity of intrathecal FLCK for any inflammatory intrathecal process was higher than that of OCB (83% vs. 38%). Intrathecal FLCK synthesis was found to discriminate AIE+ from non-inflammatory encephalopathies and AIE- when the CSF cell count was normal [receiver operating characteristic (ROC) analysis area under the curve (AUC): 0.867, p = 0.002], while it failed to differentiate between AIE+ and INE in the presence of CSF pleocytosis (AUC: 0.561, p = 0.607). In conclusion, in the absence of CSF pleocytosis, intrathecal FLCK discriminated AIE+ from competing diagnoses in our cohort of subacute onset neuropsychiatric syndromes. In addition to established markers of CSF inflammation, intrathecal FLCK might support clinical decision-making and contribute to selecting patients for (repeated) antibody testing.

Project description:IntroductionMany patients are referred to multiple sclerosis (MS) tertiary centers to manage brain white matter hyperintensities (WMH). Multiple diagnoses can match in such situations, and we lack proper tools to diagnose complex cases.ObjectiveThis study aimed to prospectively analyze and correlate with the final diagnosis, cerebrospinal fluid (CSF) interleukin (IL)-1β, soluble IL-2 receptor (CD25), IL-6, IL-10, and kappa free light chains (KFLC) concentrations in patients presenting with brain WMH.MethodsAll patients over 18 years addressed to our MS tertiary center for the diagnostic workup of brain WMH were included from June 1, 2020, to June 1, 2021. Patients were separated into three groups-MS and related disorder (MSARD), other inflammatory neurological disorder (OIND), and non-inflammatory neurological disorder (NIND) groups-according to clinical presentation, MRI characteristics, and biological workup.ResultsA total of 176 patients (129 women, mean age 45.8 ± 14.7 years) were included. The diagnosis was MSARD (n = 88), OIND (n = 35), and NIND (n = 53). Median CSF KFLC index and KFLC intrathecal fraction (IF) were higher in MSARD than in the OIND and NIND groups; p < 0.001 for all comparisons. CSF CD25 and IL-6 concentrations were higher in the OIND group than in both the MSARD and NIND groups; p < 0.001 for all comparisons. KFLC index could rule in MSARD when compared to NIND (sensitivity, 0.76; specificity, 0.91) or OIND (sensitivity, 0.73; specificity, 0.76). These results were similar to those with oligoclonal bands (sensitivity, 0.59; specificity, 0.98 compared to NIND; sensitivity, 0.59; specificity, 0.88 compared to OIND). In contrast, elevated CSF CD25 and IL-6 could rule out MSARD when compared to OIND (sensitivity, 0.58 and 0.88; specificity, 0.95 and 0.74, respectively).DiscussionOur results show that, as OCBs, KFLC biomarkers are helpful tools to rule in MSARD, whereas elevated CSF CD25 and IL-6 rule out MSARD. Interestingly, CSF IL-6 concentration could help identify neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, and central nervous system (CNS) vasculitis. These results need to be confirmed within more extensive and multicentric studies. Still, they sustain that KFLC, CSF CD25, and CSF IL-6 could be reliable biomarkers in brain WMH diagnostic workup for differentiating MSARD from other brain inflammatory MS mimickers.

Dataset Information

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

Publications

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

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