scholarly journals Cerebrospinal Fluid Biomarkers in Relation to MRZ Reaction Status in Primary Progressive Multiple Sclerosis

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2543
Author(s):  
Tilman Robinson ◽  
Ahmed Abdelhak ◽  
Tanima Bose ◽  
Edgar Meinl ◽  
Markus Otto ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
B Cell ◽  
Clinical Features ◽  
Cell Activity ◽  
Csf Biomarkers ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Mrz Reaction ◽  
Igg Synthesis

The MRZ reaction (MRZR) comprises the three antibody indices (AIs) against measles, rubella, and varicella zoster virus, reflecting an intrathecal polyspecific B cell response highly specific for multiple sclerosis (MS). Thus, MRZR can be used to confirm a diagnosis of primary progressive MS (PPMS) but its pathophysiological and wider clinical relevance is unclear. This study aimed to investigate whether PPMS patients with a positive MRZR (MRZR+) differ from those with a negative MRZR (MRZR-) according to cerebrospinal fluid (CSF) biomarkers of B cell activity, neuroaxonal damage or glial activity, and clinical features. (1) Methods: In a multicenter PPMS cohort (n = 81) with known MRZR status, we measured B cell-activating factor (BAFF), chemokine CXC ligand 13 (CXCL-13), soluble B cell maturation antigen (sBCMA), soluble transmembrane activator and CAML interactor (sTACI), and chitinase-3-like protein 1 (CHI3L1) in the CSF with enzyme-linked immunosorbent assays (ELISAs). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were detected in serum and CSF using single molecule array (SIMOA) technology. (2) Results: MRZR+ patients (45.7% of all PPMS patients) revealed higher levels of NfL in CSF compared to MRZR- patients (54.3%). There were positive correlations between each of sBCMA, sTACI, and intrathecal immunoglobin G (IgG) synthesis. Additionally, NfL concentrations in serum positively correlated with those in CSF and those of GFAP in serum. However, MRZR+ and MRZR- patients did not differ concerning clinical features (e.g., age, disease duration, Expanded Disability Status Scale (EDSS) at diagnosis and follow-up); CSF routine parameters; CSF concentrations of BAFF, CXCL-13, sBCMA, sTACI, CHI3L1, and GFAP; or serum concentrations of GFAP and NfL. (3) Conclusions: In PPMS patients, MRZR positivity might indicate a more pronounced axonal damage. Higher levels of the soluble B cell receptors BCMA and transmembrane activator and CAML interactor (TACI) in CSF are associated with a stronger intrathecal IgG synthesis in PPMS.

scholarly journals Multi-Platform Characterization of Cerebrospinal Fluid and Serum Metabolome of Patients Affected by Relapsing–Remitting and Primary Progressive Multiple Sclerosis

2020 ◽  
Vol 9 (3) ◽  
pp. 863 ◽  
Author(s):  
Federica Murgia ◽  
Lorena Lorefice ◽  
Simone Poddighe ◽  
Giuseppe Fenu ◽  
Maria Antonietta Secci ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Analytical Techniques ◽  
Roc Curves ◽  
Progressive Multiple Sclerosis ◽  
Glutathione Metabolism ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Relapsing Remitting ◽  
Pathways Analysis

Background: Multiple sclerosis (MS) is a chronic immunemediated disease of the central nervous system with a highly variable clinical presentation and disease progression. In this study, we investigate the metabolomics profile of patients affected by relapsing–remitting MS (RRMS)and primary progressive MS (PPMS), in order to find potential biomarkers to distinguish between the two forms. Methods: Cerebrospinal Fluid CSF and blood samples of 34 patients (RRMS n = 22, PPMS n = 12) were collected. Nuclear magnetic resonance (1H-NMR) and mass spectrometry (coupled with a gas chromatography and liquid chromatography) were used as analytical techniques. Subsequently, a multivariate statistical analysis was performed; the resulting significant variables underwent U-Mann–Whitney test and correction for multiple comparisons. Receiver Operating Characteristic ROC curves were built and the pathways analysis was conducted. Results: The analysis of the serum and the CSF of the two classes, allowed the identification of several altered metabolites (lipids, biogenic amines, and amino acids). The pathways analysis indicated the following pathways were affected: Glutathione metabolism, nitrogen metabolism, glutamine–glutamate metabolism, arginine–ornithine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis etc. Conclusion: The analysis allowed the identification of a set of metabolites able to classify RRMS and PPMS patients, each of whom express different patterns of metabolites in the two biofluids.

Ocrelizumab: A New B-cell Therapy for Relapsing Remitting and Primary Progressive Multiple Sclerosis

2017 ◽  
Vol 52 (5) ◽  
pp. 473-483 ◽  
Author(s):  
Amanda M. Stahnke ◽  
Kathryn M. Holt
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
English Language ◽  
Data Extraction ◽  
Progressive Multiple Sclerosis ◽  
Phase Iii ◽  
Primary Progressive Multiple Sclerosis ◽  
Two Phase ◽  
Primary Progressive ◽  
Relapsing Remitting

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of ocrelizumab, a new B-cell–targeted therapy for multiple sclerosis (MS). Data Sources: A comprehensive search of PubMed and OVID/MEDLINE was conducted using search terms ocrelizumab and multiple sclerosis using the date range of 1946 through October 2017. Study Selection and Data Extraction: All English-language, human-subject articles related to ocrelizumab and MS were evaluated. Data Synthesis: Ocrelizumab was approved in March 2017 for the treatment of relapsing or primary progressive MS (PPMS). A phase II trial established 600 mg intravenously every 6 months as the preferred dosing schedule. Two phase III trials evaluated the efficacy of ocrelizumab in patients with relapsing remitting MS, and individual and pooled analysis demonstrated a significant reduction in annualized relapse rate ( P < 0.001 pooled), disability progression at 12 weeks ( P < 0.001 pooled), and gadolinium-enhancing lesions on magnetic resonance imaging (MRI; P < 0.001). Patients with PPMS were evaluated in a third phase III trial, which showed a significant decrease in disease progression at 12 weeks ( P = 0.03) and volume of T2-weighted lesions on MRI ( P < 0.001). As with other monoclonal antibodies, adverse effects seen with ocrelizumab were primarily infusion-related reactions and infection. Conclusions: Ocrelizumab demonstrated efficacy in the treatment of relapsing and PPMS and is the first therapy approved for patients with PPMS.

scholarly journals The MRZ reaction in primary progressive multiple sclerosis

2017 ◽  
Vol 14 (1) ◽  
Author(s):  
Tilman Hottenrott ◽  
Rick Dersch ◽  
Benjamin Berger ◽  
Sebastian Rauer ◽  
Daniela Huzly ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Mrz Reaction
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