Intrathecal synthesis of antiviral IgG antibodies in multiple sclerosis.

Abstract

The Measles-Rubella-Zoster (MRZ) reaction is a test for the intrathecal synthesis of IgG antibodies against measles, rubella and varicella zoster viruses. Since the 1990s, it has been used as an adjunctive test to support the diagnosis of multiple sclerosis (MS), although it has no formal role in current McDonald diagnostic criteria and its clinical relevance remains debated. While early studies considered a single elevated antibody index (M, R or Z) as a positive result, the practice today requires at least two elevated antibody indices (M+R, M+Z, or R+Z), referred to as a polyspecific MRZ reaction (MRZ-2). MRZ-2 is the most specific laboratory marker for MS, with reported specificity exceeding 90%. However, sensitivity varies widely across studies, ranging from approximately 30% to over 70%. In the Czech adult MS population, MRZ-2 sensitivity was recently reported at 32%, markedly lower than the 67% pooled sensitivity reported in a meta-analysis of predominantly German cohorts. Broadening the panel of anti-viral antibodies (MRZ+) has been proposed to improve sensitivity, with parvovirus B19 and mumps virus being the most promising candidates. Further studies are required to determine whether an extended panel can increase sensitivity while maintaining high diagnostic specificity.