Cerebrospinal Fluid Biomarkers in Relation to MRZ Reaction Status in Primary Progressive Multiple Sclerosis
Clinic of Neurology and Neurophysiology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79085 Freiburg, Germany
Department of Neurology, University Hospital Ulm, 89081 Ulm, Germany
Biomedical Center and Klinikum Grosshadern, Institute of Clinical Neuroimmunology, Ludwig Maximilian University, 81377 Munich, Germany
Neuroimmunological Section, Department of Neurology, Medical Center of the University of Rostock, 18051 Rostock, Germany
Specialty Hospital Dietenbronn, 88477 Schwendi, Germany
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(12), 2543; https://doi.org/10.3390/cells9122543
Received: 8 September 2020 / Revised: 5 November 2020 / Accepted: 20 November 2020 / Published: 25 November 2020
(This article belongs to the Special Issue The Molecular and Cellular Basis for Multiple Sclerosis - Series 2)
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.
Keywords: MRZ reaction (MRZR); primary progressive multiple sclerosis (PPMS); B cell-activating factor (BAFF); chemokine CXC ligand 13 (CXCL-13); soluble B cell maturation antigen (sBCMA); soluble transmembrane activator and CAML interactor (sTACI); chitinase-3-like protein 1 (CHI3L1); glial fibrillary acidic protein (GFAP); neurofilament light chain (NfL)