- •Immunoglobulin free light chains (FLC) are promising intrathecal biomarkers of MS.
- •As lumbar puncture is an invasive procedure, it is not applicable for disease monitoring.
- •We assessed the utility of saliva FLC as a potential biomarker of MS.
- •Results show that saliva FLC levels may discriminate between stable remission and active disease.
- •The test may serve as a new, non-invasive, and inexpensive tool for monitoring disease activity.
Immunoglobulin free light chains (FLC) have recently gained considerable interest as new promising intrathecal biomarkers of multiple sclerosis (MS). However, lumbar puncture is invasive and not practical for monitoring disease course. This study aimed to assess the utility of saliva FLC as a biomarker of disease activity and response to treatment in MS
Western blotting was used to study saliva FLC monomers and dimers. The intensity of immunoreactive FLC bands was quantified by electrophoresis analysis, and the obtained values were used as FLC indices to account for kappa and lambda FLC monomer and dimer levels. Firth's logistic regression analysis suitable to study small cohorts was applied to compare FLC levels between M.S. patients in relapse, MS patients in remission, and healthy controls. Association between FLC levels and clinical and radiological parameters was analyzed.
55 MS patients and 40 healthy controls were evaluated. Saliva FLC levels were significantly higher in relapse compared to remission. Logistic regression analysis employing a combination of FLC indices confirmed the significant difference between these two groups. The FLC levels were significantly reduced by treatment with corticosteroids. During remission, patients treated with disease-modifying therapies had lower levels of FLC compared to untreated patients. The increased FLC levels were associated with the presence of gadolinium-enhancing lesions, but not with MRI T2 lesion load and EDSS scores. During individual patient follow-up, the changes of the saliva FLC levels were in concordance with the disease activity status.
Saliva FLC levels may be a useful biomarker for discriminating between stable remission and active disease. The developed test may serve as a new, non-invasive, and inexpensive tool for monitoring disease activity and response to treatment in MS.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Multiple Sclerosis and Related Disorders
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Clinical use of kappa free light chains index as a screening test for multiple sclerosis.Lab. Med. 2020;
- Free light chains in cerebrospinal fluid of multiple sclerosis patients negative for IgG oligoclonal bands.Clin. Chim. Acta. 2019; 496: 117-120
- Tear analysis in clinically isolated syndrome as new multiple sclerosis criterion.Mult. Scler. 2010; 16: 87-92
- Kappa free light chains index in the differential diagnosis of multiple sclerosis from neuromyelitis optica spectrum disorders and other immune-mediated central nervous system disorders.J. Neuroimmunol. 2020; 339577122
- Cerebrospinal fluid free kappa light chains and kappa index perform equal to oligoclonal bands in the diagnosis of multiple sclerosis.Clin. Chem. Lab. Med. 2018;
- Precision medicine in multiple sclerosis: biomarkers for diagnosis, prognosis, and treatment response.Curr. Opin. Neurol. 2016; 29: 254-262
- Multiple sclerosis.Lancet. 2008; 372: 1502-1517
- Immune-reactive cells in multiple sclerosis mucosal secretions.Neurology. 1989; 39: 378-380
- Increased monomeric immunoglobulin a levels in tears from multiple sclerosis patients.Ann. Neurol. 1987; 21: 211-214
- K index is a reliable marker of intrathecal synthesis, and an alternative to IgG index in multiple sclerosis diagnostic work-up.J. Clin. Med. 2019; 8
- Induction therapy for the management of early relapsing forms of multiple sclerosis.A crit. opin. Expert Opin. Pharmacother. 2017; 18: 1553-1556
- Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude.J. Neurol. Neurosurg. Psychiatry. 2013; 84: 909-914
- Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band-negative patients with suspected multiple sclerosis.Eur. J. Neurol. 2020; 27: 461-467
- Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines.Brain. 2019;
- Cerebrospinal fluid free light chains compared to oligoclonal bands as biomarkers in multiple sclerosis.J. Neuroimmunol. 2020; 339577108
- Personalised medicine for multiple sclerosis care.Mult. Scler. 2017; 23: 362-369
- Relapse in multiple sclerosis.BMJ. 2015; 350: h1765
- CSF free light chain identification of demyelinating disease: comparison with oligoclonal banding and other CSF indexes.Clin. Chem. Lab. Med. 2018; 56: 1071-1080
- Free light chain monomers in the diagnosis of multiple sclerosis.J. Neuroimmunol. 2010; 229: 263-271
- Diagnostic utility of kappa free light chains in multiple sclerosis.Expert Rev. Mol. Diagn. 2019; 19: 277-279
- Immunoglobulin free light chains in saliva: a potential marker for disease activity in multiple sclerosis.Clin. Exp. Immunol. 2018; 192: 7-17
- Free light chain monomer-dimer patterns in the diagnosis of multiple sclerosis.J. Immunol. Methods. 2013; 390: 74-80
- Epidemiology of multiple sclerosis.Rev. Neurol. (Paris). 2016; 172: 3-13
- Kappa free light chains is a valid tool in the diagnostics of MS: a large multicenter study.Mult. Scler. 2019; 1352458519845844
- Cerebrospinal fluid analysis in multiple sclerosis diagnosis: an update.Medicina (Kaunas). 2019; 55
- Does CSF pleocytosis have a predictive value for disease course in MS?.Neurol.(R) Neuroimmunol. Neuroinflamm. 2019; 6: e584
- Can CSF biomarkers predict future MS disease activity and severity?.Mult. Scler. 2020; 1352458519871818
- Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: A systematic review.Autoimmun. Rev. 2017; 16: 658-665
- Concentrations of immunoglobulin free light chains in cerebrospinal fluid predict increased level of brain atrophy in multiple sclerosis.Immunol. Res. 2018; 66: 761-767
- Established disease-modifying treatments in relapsing-remitting multiple sclerosis.Curr. Opin. Neurol. 2015; 28: 220-229
- Multiple sclerosis: clinical aspects.Curr. Opin. Neurol. 2018; 31: 752-759
- KFLC Index utility in multiple sclerosis diagnosis: Further confirmation.J. Neuroimmunol. 2017; 309: 31-33
- Intrathecal K free light chain synthesis in multiple sclerosis at clinical onset associates with local IgG production and improves the diagnostic value of cerebrospinal fluid examination.Mult. Scler. Relat. Disord. 2018; 25: 241-245
- Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis.J. Neurol. Neurosurg. Psychiatry. 2018; 89: 1044-1049
- Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires.J. Neurol. 2018;
- CSF free light chains as a marker of intrathecal immunoglobulin synthesis in multiple sclerosis: a blood-csf barrier related evaluation in a large cohort.Front. Immunol. 2019; 10: 641
- Kappa free light chains in cerebrospinal fluid to identify patients with oligoclonal bands.Eur. J. Neurol. 2018; 25: 1134-1139
- Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.Lancet Neurol. 2018; 17: 162-173
- Multiple sclerosis.Lancet. 2018; 391: 1622-1636
- Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis?.Neurology. 2008; 70: 1079-1083
- Mucosal-associated invariant T cells in multiple sclerosis: the jury is still out.Front. Immunol. 2015; 6: 503
- Update on disease-modifying therapies for multiple sclerosis.J. Investig. Med. 2017; 65: 883-891
- Relevance of KFLC quantification to differentiate clinically isolated syndrome from multiple sclerosis at clinical onset.Clin. Neurol. Neurosurg. 2018; 174: 220-229
- Kappa free light chains could predict early disease course in multiple sclerosis.Mult Scler Relat Disord. 2019; 30: 81-84
- Prognostic value of free light chains lambda and kappa in early multiple sclerosis.Mult. Scler. 2017; 23: 1496-1505
- Optimizing therapy early in multiple sclerosis: an evidence-based view.Mult. Scler. Relat. Disord. 2015; 4: 460-469
Published online: June 24, 2020
Accepted: June 23, 2020
Received in revised form: June 14, 2020
Received: May 1, 2020
© 2020 Elsevier B.V. All rights reserved.