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MRZ-reaction maybe influenced by immunization status and is not exclusive to multiple sclerosis
Mary Anitha D'Cunha1, Lekha Pandit1, Akshatha Sudhir1
1Center for Advanced Neurological Research, Nitte University, Mangalore,India.
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.
Insights
In a South Indian cohort, measles, rubella, and varicella zoster (MRZR) antibodies were found in 50% of multiple sclerosis (MS) patients, potentially influenced by community infections rather than vaccination. Oligoclonal bands (OCB) were more sensitive and specific for MS.
Area of Science:
- Neuroimmunology
- Infectious Immunology
Background:
- A poly-specific antibody response against measles (M), rubella (R), and varicella zoster (Z), known as MRZR, is observed in approximately 70% of multiple sclerosis (MS) patients in white populations.
- The underlying reasons for MRZR positivity remain unclear, with vaccination exposure or community-acquired infections suspected as potential influencing factors.
Purpose of the Study:
- To investigate the frequency and specificity of MRZR in MS and related neurological disorders within a non-white population in South India, characterized by historically low vaccination rates.
- To compare the diagnostic utility of MRZR with oligoclonal bands (OCB) in this population.
Main Methods:
- A cohort of 167 patients, including those with MS (n=96), MOGAD (n=33), AQP4-IgG+ NMOSD (n=12), and double seronegative disorders (DSD, n=26), were analyzed.
- Data on clinical diagnosis, vaccination history, and past infections were collected. MRZR antibody levels and OCB results were measured and reviewed.
Main Results:
- MRZR positivity was detected in 50% of MS patients, 21.2% with MOGAD, 8.3% with NMOSD, and 3.8% with DSD.
- A history of varicella zoster (Z) infection was significantly associated with MRZR-Z positivity (p=0.005), and a high median antibody index for Z and R was observed in MS patients (p=0.001).
- In MS patients, CSF-specific OCB demonstrated higher sensitivity (71.9%) and specificity (94.4%) compared to MRZR (sensitivity 50%, specificity 87.3%).
Conclusions:
- Community-acquired immunity, rather than vaccination, may contribute to MRZR positivity, particularly MRZR-Z, in this South Indian cohort with low vaccination rates.
- A chronic inflammatory state, potentially not disease-specific, appears to be a prerequisite for MRZR positivity in CNS disorders with overlapping immunological profiles, such as MS and MOGAD.
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