Saliva immunoglobulin free light chain analysis for monitoring disease activity and response to treatment in multiple sclerosis.


Journal

Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247

Informations de publication

Date de publication:
Sep 2020
Historique:
received: 01 05 2020
revised: 14 06 2020
accepted: 23 06 2020
pubmed: 1 7 2020
medline: 15 5 2021
entrez: 30 6 2020
Statut: ppublish

Résumé

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 METHODS: 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.

Sections du résumé

BACKGROUND BACKGROUND
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 METHODS: 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.
RESULTS RESULTS
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.
CONCLUSIONS CONCLUSIONS
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.

Identifiants

pubmed: 32599469
pii: S2211-0348(20)30415-6
doi: 10.1016/j.msard.2020.102339
pii:
doi:

Substances chimiques

Immunoglobulin Light Chains 0
Immunoglobulin kappa-Chains 0
Immunoglobulin lambda-Chains 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

102339

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Auteurs

Itay Lotan (I)

Department of Neurology, Rabin Medical Center, Beilinson Hospital, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel. Electronic address: lotan.itay1@gmail.com.

Esther Ganelin-Cohen (E)

Sackler Faculty of Medicine, Tel-Aviv University, Israel; Institute of Pediatric Neurology, Schneider Children's Medical Center, Petach Tikva 49202, Israel.

Evgeny Tartakovsky (E)

Tartakovsky MLD Consultancy, P.O. Box 71, Rishon Lezion, 7510001, Israel.

Vadim Khasminsky (V)

Sackler Faculty of Medicine, Tel-Aviv University, Israel; Department of Radiology, Rabin Medical Center, Beilinson Hospital, Israel.

Mark A Hellmann (MA)

Department of Neurology, Rabin Medical Center, Beilinson Hospital, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel.

Israel Steiner (I)

Department of Neurology, Rabin Medical Center, Beilinson Hospital, Israel; Tartakovsky MLD Consultancy, P.O. Box 71, Rishon Lezion, 7510001, Israel.

Ilan Ben-Zvi (I)

Sackler Faculty of Medicine, Tel-Aviv University, Israel; Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer, Israel.

Avi Livneh (A)

Sackler Faculty of Medicine, Tel-Aviv University, Israel; Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer, Israel.

Sizilia Golderman (S)

Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer, Israel.

Batia Kaplan (B)

Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer, Israel.

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Classifications MeSH