Free light chains as a reliable biomarker of intrathecal synthesis in the diagnosis of CNS inflammatory diseases

Michetti, L; Maffina, Francesca; Ravasio, Rudi; Barcella, Valeria; Radaelli, Marta; Chiudinelli, Lorenzo; Sessa, Maria; Alessio, Maria Grazia

doi:10.1016/j.jneuroim.2023.578091

Cited by 3 publications

(5 citation statements)

References 40 publications

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“…Previous studies on CSF oligoclonal bands (OCB) in patients with viral encephalitis have shown significant variations in the reported results. In studies of viral encephalitis in adults, domestic studies have reported OCB positivity rates of 47.6% for inflammatory neurological diseases of the central nervous system [12], while foreign scholars, Bourahoui et al, reported OCB positivity rates of 30% to 50% for CNS inflammatory diseases [7]. Jinxing Wang et al [9] reported an OCB positivity rate of 23.33% for CNS infectious diseases, which was lower compared to previous reports.…”

Section: Discussionmentioning

confidence: 86%

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The Diagnostic Value of Oligoclonal Band Detection in Viral Encephalitis

Huang,

Meng,

2024

JBBS

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Objective: This study aims to explore the differences in cerebrospinal fluid oligoclonal band (CSF-OCB) expression among different age groups in viral encephalitis and its reference value for diagnosis. Methods: Forty-two patients with viral encephalitis were divided into two groups: 25 adults and 17 children. The presence of oligoclonal bands in the cerebrospinal fluid (CSF) was detected using polyacrylamide gel electrophoresis, and CSF routine analysis was conducted for comparative analysis. Results: The CSF-OCB positivity rate was higher in the adult group (48%) compared with the pediatric group (11.76%), with a statistically significant difference (P < 0.05). There was no significant difference in adult group between the CSF-OCB positivity rate (48%) and CSF white blood cell count positivity rate (44%), but was higher than the protein quantification analysis positivity rate (20%), with statistical significance (P < 0.05). In the pediatric group, there was no significant difference between the CSF-OCB positivity rate (11.76%) and protein quantification analysis positivity rate (17.65%), but it was lower than the CSF white blood cell count positivity rate (64.71%) (P < 0.05). Conclusion: 1) The expression of CSF-OCB positivity in patients with viral encephalitis is age-related, with higher positivity rates observed in adults compared to children. 2) Although CSF oligoclonal band detection is not a specific diagnostic marker for viral encephalitis in adults, it still holds certain reference value.

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Section: Discussionmentioning

confidence: 86%

“…In recent years, there have been reports both domestically and internationally [7] [8] [9] [10] investigating the expression of CSF-OCBs in patients with viral encephalitis. However, there is lack of studies comparing the differences in CSF-OCB expression between adult and pediatric patients with viral encephalitis.…”

Section: Introductionmentioning

confidence: 99%

The Diagnostic Value of Oligoclonal Band Detection in Viral Encephalitis

Huang,

Meng,

2024

JBBS

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“…Generally, a kFLC index cut-off equal to 4.7, compared to the OCB and IgG index, showed greater sensitivity (92.9%) but lower specificity (77.5%) [28]. In addition, considering the advantages regarding the use of the K-index (rapid and automated technique) compared to OCBs, some authors have proposed the use of the K-index as a primary marker instead of the evaluation of OCBs to highlight the intrathecal synthesis of IgG [3,28,38,61].…”

Section: Diagnostic Performance Of Ocbs and K-index In Msmentioning

confidence: 90%

“…As a result, according to a recent study, CSF kFLC concentration is higher in MS patients compared to the other groups such as those with immune-mediated CNS disorders (IND), peripheral inflammatory disorders (PIND), non-immune-mediated neurological disorders (NIND), and symptomatic controls (SC), while no differences were found in serum FLCs. On the other hand, CSF λFLC concentration is higher in immune-mediated CNS disorder (IND) patients compared to MS and the other groups [28]. Moreover, recent studies have suggested that FLCs in CSF is a reliable marker of intrathecal immune activation, especially the K-FLC, which is normalized for to albumin quotient [18,22].…”

Section: The Role Of Kflc In Csf: a Significative Fluid Biomarkermentioning

confidence: 99%

“…The storage temperature depends on the analytes that needs to be analyzed: immunoglobulins (Ig) can be measured many years after storage at −20 • C, while other proteins, if not analyzed within 2 months, require a storage temperature of −80 • C. To ensure the stability of all markers, a storage temperature of −80 • C is recommended [53]. The detailed laboratory procedures reported in Table 1 reveal variations in storage methods: some authors stored the centrifugated cerebrospinal fluid samples at −80 • C [44,[51][52][53]56] and others used samples that were centrifuged and stored at −20 • C until the moment of analysis [28,[36][37][38]. Two papers described that the samples were immediately processed after collection [50,54], while one article reported that analyzed samples were processed two hours after collection and stored at 4 • C [57].…”

Section: Laboratory Proceduresmentioning

confidence: 99%

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Laboratory Diagnosis of Intrathecal Synthesis of Immunoglobulins: A Review about the Contribution of OCBs and K-index

Morello,

Mastrogiovanni,

Falcione

et al. 2024

IJMS

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The diagnosis of MS relies on a combination of imaging, clinical examinations, and biological analyses, including blood and cerebrospinal fluid (CSF) assessments. G-Oligoclonal bands (OCBs) are considered a “gold standard” for MS diagnosis due to their high sensitivity and specificity. Recent advancements have involved the introduced of kappa free light chain (k-FLC) assay into cerebrospinal fluid (CSF) and serum (S), along with the albumin quotient, leading to the development of a novel biomarker known as the “K-index” or “k-FLC index”. The use of the K-index has been recommended to decrease costs, increase laboratory efficiency, and to skip potential subjective operator-dependent risk that could happen during the identification of OCBs profiles. This review aims to provide a comprehensive overview and analysis of recent scientific articles, focusing on updated methods for MS diagnosis with an emphasis on the utility of the K-index. Numerous studies indicate that the K-index demonstrates high sensitivity and specificity, often comparable to or surpassing the diagnostic accuracy of OCBs evaluation. The integration of the measure of the K-index with OCBs assessment emerges as a more precise method for MS diagnosis. This combined approach not only enhances diagnostic accuracy, but also offers a more efficient and cost-effective alternative.

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Prospective multicenter validation of a new laboratory workflow integrating the free light chains kappa quotient in CSF analysis-Protocol of the ORCAS study

Dressel

Hannich

Suesse

2023

Preprint

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Introduction: Free light chain kappa (FLCκ) are a newer sensitive biomarker to detect intrathecal immunoglobulin synthesis. Here we report the study protocol of the ORCAS study which will evaluate a novel laboratory work flow recently proposed including FLCκ analysis simplifying cerebrospinal fluid (CSF) analysis. Methods: The ORCAS study is a prospective multicenter diagnostic biomarker study across at least 4 study sites. The study protocol does not specify which assays should be applied in the participating laboratories to detect oligoclonal bands (OCB) or measure FLCκ or Ig synthesis to represent real world data. Primary outcome parameter is the sensitivity and negative predictive value of the absence of local FLCκ synthesis for the absence of intrathecal synthesis according to OCB and/or intrathecal IgG, IgA, IgM synthesis in quotient diagrams. The reference range of FLCκ will be indicated by the FLCκ quotient diagram. This study was designed according to the STARD criteria. Perspective: The establishment of a newer biomarker in routine practice is associated with significant difficulties, such as the inconsistent comparability of different measurement platforms, the establishment of suitable cut-offs or insufficient knowledge regarding sensitivity and specificity of the biomarker. If the ORCAS study objective is achieved, the use of the proposed workflow integrating FLCκ analysis in routine practice in CSF diagnostics could help to better characterize the intraindividual and disease-specific intrathecal humoral immune response in a resource-efficient manner.

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Free light chains as a reliable biomarker of intrathecal synthesis in the diagnosis of CNS inflammatory diseases

Cited by 3 publications

References 40 publications

The Diagnostic Value of Oligoclonal Band Detection in Viral Encephalitis

The Diagnostic Value of Oligoclonal Band Detection in Viral Encephalitis

Laboratory Diagnosis of Intrathecal Synthesis of Immunoglobulins: A Review about the Contribution of OCBs and K-index

Prospective multicenter validation of a new laboratory workflow integrating the free light chains kappa quotient in CSF analysis-Protocol of the ORCAS study

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