Itay Lotan1, Esther Ganelin-Cohen2, Evgeny Tartakovsky3, Vadim Khasminsky4, Mark A Hellmann5, Israel Steiner6, Ilan Ben-Zvi7, Avi Livneh7, Sizilia Golderman8, Batia Kaplan8. 1. Department of Neurology, Rabin Medical Center, Beilinson Hospital, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel. Electronic address: lotan.itay1@gmail.com. 2. Sackler Faculty of Medicine, Tel-Aviv University, Israel; Institute of Pediatric Neurology, Schneider Children's Medical Center, Petach Tikva 49202, Israel. 3. Tartakovsky MLD Consultancy, P.O. Box 71, Rishon Lezion, 7510001, Israel. 4. Sackler Faculty of Medicine, Tel-Aviv University, Israel; Department of Radiology, Rabin Medical Center, Beilinson Hospital, Israel. 5. Department of Neurology, Rabin Medical Center, Beilinson Hospital, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel. 6. Department of Neurology, Rabin Medical Center, Beilinson Hospital, Israel; Tartakovsky MLD Consultancy, P.O. Box 71, Rishon Lezion, 7510001, Israel. 7. Sackler Faculty of Medicine, Tel-Aviv University, Israel; Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer, Israel. 8. Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer, Israel.
Abstract
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: 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: 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.
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: 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: 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.
Authors: Franz Felix Konen; Philipp Schwenkenbecher; Konstantin Fritz Jendretzky; Stefan Gingele; Kurt-Wolfram Sühs; Hayrettin Tumani; Marie Süße; Thomas Skripuletz Journal: Cells Date: 2021-11-06 Impact factor: 6.600