IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome.
BACKGROUND
Multiple sclerosis (MS) is characterized by a polyspecific B-cell response to neurotropic viruses such as measles, rubella and varicella zoster, with the corresponding antibodies measurable in CSF as the so-called "MRZ reaction" (MRZR). We aimed to evaluate the relevance of MRZR to predict conversion of patients with clinically isolated syndrome (CIS) to MS, and to compare it to oligoclonal bands (OCB) and MRI.


RESULTS
MRZR was determined in a prospective study over 2 years including 40 patients that remained CIS over follow-up (CIS-CIS) and 49 patients that developed MS (CIS-RRMS) using ELISA. Using logistic regression, a score (MRZS) balancing the predictive value of the antibody indices included in MRZR was defined (9 points measles, 8 points rubella, 1 point varicella zoster, cutpoint: sum of scores greater 10). MRZR and MRZS were significantly more frequent in CIS-RRMS as compared to CIS-CIS (p=0.04 and p=0.02). MRZS showed the best positive predictive value (PPV) of all parameters investigated (79%, 95%-CI: 54-94%), which could be further increased by combination with MRI (91%, 95%-CI: 59-99%).


CONCLUSIONS
Our data indicate the relevance of MRZR to predict conversion to MS. It furthermore shows the importance of weighting the different antibody indices included in MRZR and suggest that patients with positive MRZR are candidates for an early begin of immunomodulatory therapy.
Brettschneider
Johannes
J
Department of Neurology, University of Ulm, Ulm, Germany.
Tumani
Hayrettin
H
Kiechle
Ulrike
U
Muche
Rainer
R
Richards
Gayle
G
Lehmensiek
Vera
V
Ludolph
Albert C
AC
Otto
Markus
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D014645:Herpesvirus 3, Human / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008459:Measles virus / Q000276:immunology* / Q000378:metabolism*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000821:virology*; D011446:Prospective Studies; D012412:Rubella virus / Q000276:immunology* / Q000378:metabolism*
D007074:Immunoglobulin G