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

Crespi, Ilaria; Vecchio, Domizia; Serino, R.; Saliva, Elena; Virgilio, Eleonora; Sulas, Maria Giovanna; Bellomo, Giorgio; Dianzani, Umberto; Cantello, Roberto; Comi, Cristoforo

doi:10.3390/jcm8040446

Cited by 34 publications

(46 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The cut-off for KFLC index we employed was 5.0. This value showed the greatest combination of sensitivity and specificity in our population 2 , 3 . Regarding KFLC, other approaches have been studied to calculate the intrathecal fraction including different cut-offs of the index, Reiber's diagram, Presslauer's exponential curve, and Senel's linear curve 9 .…”

Section: Methodsmentioning

confidence: 74%

“…Kappa free light chains (KFLC) index has been described as a reliable marker of intrathecal immunoglobulin G (IgG) synthesis in multiple sclerosis (MS), resulting even more accurate than IgG index to discriminate MS from other neurological diseases 1 – 3 . Immunoglobulin free light chains (FLC), both of kappa and lambda subtypes, are produced by B-lymphocytes during antibody synthesis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intrathecal kappa free light chains as markers for multiple sclerosis

Vecchio

Bellomo

Serino

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Cerebrospinal 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.

show abstract

Section: Methodsmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Intrathecal kappa free light chains as markers for multiple sclerosis

Vecchio

Bellomo

Serino

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Free light chains that occur either as κ- or λ-isotype are secreted in excess over intact immunoglobulins by terminally differentiated B cells 25 and accumulate in the CSF in case of intrathecal inflammation, as this is the case in chronic inflammatory CNS diseases such as MS. Intrathecal κ-FLC synthesis determined by an increased κ-FLC index was proven as a reliable diagnostic biomarker in MS performing similar to OCB. 8 , 9 , 26 - 30 However, only a few previous studies have investigated the prognostic value of κ-FLC in MS, some with considerable limitations. These include measuring κ-FLC concentrations only in CSF 10 , 31 - 33 or calculating the CSF/serum ratio 10 , 34 without reference to the blood-CSF barrier function and mixing different MS disease courses within 1 group for statistical analysis.…”

Section: Discussionmentioning

confidence: 99%

Kappa-Free Light Chains in CSF Predict Early Multiple Sclerosis Disease Activity

Berek

Bsteh

Auer

et al. 2021

Neurol Neuroimmunol Neuroinflamm

View full text Add to dashboard Cite

ObjectiveTo investigate whether κ-free light chain (κ-FLC) index predicts multiple sclerosis (MS) disease activity independent of demographics, clinical characteristics, and MRI findings.MethodsPatients with early MS who had CSF and serum sampling at disease onset were followed for 4 years. At baseline, age, sex, type of symptoms, corticosteroid treatment, and number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CELs) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying therapy (DMT) were registered. κ-FLCs were measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient.ResultsA total of 88 patients at a mean age of 33 ± 10 years and female predominance of 68% were included; 38 (43%) patients experienced a second clinical attack during follow-up. In multivariate Cox regression analysis adjusting for age, sex, T2L, CEL, disease and follow-up duration, administration of corticosteroids at baseline and DMT during follow-up revealed that κ-FLC index predicts time to second clinical attack. Patients with κ-FLC index >100 (median value 147) at baseline had a twice as high probability for a second clinical attack within 12 months than patients with low κ-FLC index (median 28); within 24 months, the chance in patients with high κ-FLC index was 4 times as high as in patients with low κ-FLC index. The median time to second attack was 11 months in patients with high κ-FLC index whereas 36 months in those with low κ-FLC index.ConclusionHigh κ-FLC index predicts early MS disease activity.Classification of EvidenceThis study provides Class II evidence that in patients with early MS, high κ-FLC index is an independent risk factor for early second clinical attack.

show abstract

“…KFLC index has been explored as a diagnostic biomarker, despite the lack of an unequivocal cut-off value currently causes some difficulties in comparing results from several studies [ Table 2]. As an indicator of intrathecal synthesis, KFLC index correlates well with IgG index [54] , using a cut-off value of 5, although showing greater sensitivity (more than 96% vs. nearly 50%) for CSF IgG OCB identification and MS diagnosis and according to higher negative predictive values, with comparable specificity.…”

Section: Kappa Free Light Chains and Kappa Indexmentioning

confidence: 99%

“…Such a diagnostic route would allow clinicians to reduce false positive results when faced with an inflammatory disease of the CNS. Showing a comparable or higher specificity [50,54] , IgG index could still have a role as a screening test complementary to KFLC index for the detection of intrathecal Ig synthesis. However, KFLC index currently shows an intermediate level of evidence as a diagnostic biomarker, requiring other confirmatory studies in larger cohorts [3] .…”

Section: Kappa Free Light Chains and Kappa Indexmentioning

confidence: 99%

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Toscano¹,

Patti²

2020

View full text Add to dashboard Cite

For many years, quantifiable biomarkers in neurological diseases have represented a hot topic. In multiple sclerosis (MS), cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's criteria in 1983, with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and a complementary one after the introduction of McDonald criteria in 2001. Nowadays, that supporting role has turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with a first clinical event, according to the 2017 revised McDonald criteria. Possibly kappa free light chains, N-CAM, chitinase 3-like protein 1 and IgM oligoclonal bands, not yet implemented in clinical practice, could similarly gain importance in the near future. Furthermore, the increasing knowledge of molecular mechanisms leading to chronic inflammation has enhanced interest in looking for biomarkers of disease activity, better defining the MS phenotype and patients with highly active disease. Accordingly, myelin proteins, intermediate filaments, metalloproteinases and other molecules involved in the inflammatory cascade, are currently under investigation. Finally, it has long been known that axonal loss occurs from the early phases, leading to a progressive neurological deterioration. Since established criteria to assess treatment failure and transition to progressive forms are still lacking, both treatment response and prognostic biomarkers would be useful to predict MS course, and neurofilaments seem to have this potential. The purpose of this review article was to illustrate biomarkers that have been already validated or require further validation after proving to be useful in exploratory studies and potentially could prove useful in clinical practice in the coming years.

show abstract

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

Cited by 34 publications

References 18 publications

Intrathecal kappa free light chains as markers for multiple sclerosis

Intrathecal kappa free light chains as markers for multiple sclerosis

Kappa-Free Light Chains in CSF Predict Early Multiple Sclerosis Disease Activity

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Contact Info

Product

Resources

About