IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome

• Published in: PloS one Vol. 4; no. 11; p. e7638
• Main Authors: Brettschneider, Johannes, Tumani, Hayrettin, Kiechle, Ulrike, Muche, Rainer, Richards, Gayle, Lehmensiek, Vera, Ludolph, Albert C, Otto, Markus
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.11.2009; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Antibodies; Antigen-antibody reactions; Cerebrospinal fluid; Chicken pox; Chickenpox; Conversion; Disease; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunosorbent Assay - methods; Female; Herpes zoster; Herpesvirus 3, Human - metabolism; Humans; Immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulins; Immunology/Autoimmunity; Immunology/Immune Response; Immunomodulation; Lymphocytes B; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Measles; Measles virus - immunology; Measles virus - metabolism; Medical research; Middle Aged; Multiple sclerosis; Multiple Sclerosis - immunology; Multiple Sclerosis - virology; Neurological Disorders; Neurological Disorders/Multiple Sclerosis and Related Disorders; Neurological Disorders/Neuroimaging; Neurology; NMR; Nuclear magnetic resonance; Patients; Physiology; Prospective Studies; Proteins; Rubella; Rubella virus - immunology; Rubella virus - metabolism; Varicella; Viruses; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0007638

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. 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%). 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.