Biomarkers and Bioinformatics Poster Presentation

P0117 - Mystery of MRZ reaction in multiple sclerosis   (ID 1449)

Speakers
  • S. Wachamo
Authors
  • S. Wachamo
  • R. Masvekar
  • P. Kosa
  • M. Varosanec
  • B. Bielekova
Presentation Number
P0117
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Background: Multiple Sclerosis (MS) is an immune mediated disease of the central nervous system (CNS). Epstein-Barr virus (EBV) is among the most well-established environmental risk factors in MS. MS patients also make low affinity antibodies against neurotrophic viruses such as measles (M), rubella (R), and zoster (Z), and they make these intrathecally. This phenomenon is quite specific for MS and it is called MRZ reaction. The pathophysiological role of MRZ reaction currently remains unclear.

Objectives

Objectives: Because EBV induces differentiation of infected B cells in antigen-nonspecific manner, the aim of this project is to test the hypothesis that the extent of MRZ reaction correlates with the amount of EBV infected B cells in the intrathecal compartment of MS patients and with the MS severity.

Methods

Methods: In a pilot cohort of 80 patients with broad range of MS severity, we blindly analyzed MRZ reaction by enzyme-linked immunosorbent assay (ELISA) applied to matched cerebrospinal fluid (CSF) and serum samples. To derive a single measure of the extent of MRZ reaction, we summed antibody indexes (AI) for each reaction component (M, R and Z) to MRZ score.

Results

Results: Upon unblinding the MS severity outcomes and diagnostic subgroups, the MRZ scores did not significantly correlate with B cell/plasma cell biomarkers known to be increased in MS CSF (i.e., B-cell maturation antigen/BCMA and IgG index) and were not significantly different between relapsing remitting, primary progressive and secondary progressive MS. Finally, the MRZ scores did not correlate with clinical outcomes of MS severity (MS disease severity scale: MS-DSS and brain damage severity: principal component of brain parenchymal fraction and the symbol digit modalities test normalized for patient’s age).

Conclusions

Conclusions: The study proved null hypothesis (i.e., MRZ reaction is not associated with intrathecal biomarkers of B cell/plasma cell expansion and with MS severity). The association between MRZ reaction and MS remains a mystery.

Acknowledgments: The research was supported by the Intramural Research Program of the NIH, NIAID.

Notice: This study involved patients and it was approved by NIAID IRB.

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