MRZ-reaction maybe influenced by immunization status and is not exclusive to multiple sclerosis.

Background: Among white populations, a poly-specific antibody response against measles (M), rubella (R) and varicella zoster(Z) otherwise known as MRZR is seen in ∼70 % of MS and rarely in other demyelinating disorders. While the basis for MRZR is unclear, vaccination exposure / community acquired infections may have an influence on its frequency.

Objective: To determine the frequency and specificity of MRZR in MS and related disorders in a non- white population with historically low vaccinations and to contrast against oligoclonal bands (OCB).

Methods: In all, 167 consecutive patients (MS -96, MOGAD-33, AQP4-IgG + NMOSD-12 & double seronegative disorders[DSD] -26) were included. Clinical diagnosis, vaccination history and past infections contributing to MRZR were queried, OCB results were reviewed and MRZR measured.

Result: MRZR+ response was seen in 50 % MS, 21.2 % MOGAD, 8.3 %NMOSD and 3.8 % of DSN disease. Vaccination history was limited, a past history of Z was notably associated (p 0.005) with MRZR-Z+ and a high median antibody index was detected for Z and R (p 0.001) in MS. Among MRZR+ patients with MOGAD, a disseminated disease that included LETM (p 0.007), relapsing course (p 0.02), higher relapse rate (p 0.001) and lumbar puncture performed after 2 or more attacks(p 0.009) were significant. CSF specific OCB was more sensitive (71.9 %;95 %CI 61.8-80.6) and specific (94.4 %;95 %CI 86.2-98.4) than MRZR (sensitivity 50 % [95 %CI 39.62-60.4] and specificity 87.3 %(95 %CI 77.3-94.04) for MS patients.

Conclusion: In this south Indian cohort with historically low vaccination status, community acquired immunity may have in part influenced MRZR+ results, especially MRZR-Z. A chronic inflammatory state is a likely pre-requisite, that may not be disease specific, for MRZR positivity in immunologically overlapping CNS disorders such as MS, MOGAD and others.