Intrathecal immune reactivity against Measles-, Rubella-, and Varicella Zoster viruses is associated with cerebrospinal fluid inflammation in multiple sclerosis

Background/Objectives: We aimed to determine in multiple sclerosis (MS) whether intrathecal immunoglobulin G (IgG) production against measles- (M), rubella- (R), and varicella zoster (Z) viruses, which is called MRZ reaction (MRZR) and considered the most specific soluble biomarker for MS, is associated with demographic and basic cerebrospinal fluid (CSF) parameters reflecting inflammation. Methods: We analyzed the presence of positive MRZR and associations with demographic and clinical routine CSF parameters in 513 patients with MS and 182 non-MS patients. Results: Comparing MS patients versus non-MS patients, positive MRZR (38.8% versus 2.2%; specificity 97.8%; positive likelihood ratio, PLR 17.7) had a better specificity and PLR for MS than CSF-specific OCB (89.5% versus 22.0%; specificity 78.0%; PLR 4.1). A positive MRZR in MS patients was associated with female sex (p = 0.0001), pleocytosis (p < 0.0001), higher frequency of presence of plasma cells in CSF (p = 0.0248), normal CSF/serum albumin ratio (p = 0.0005), and intrathecal production of total IgG or CSF-specific OCB (both p < 0.0001), but not with intrathecal production of total IgA or IgM. Conclusions: This study confirms the MRZR as a highly specific marker of MS and shows that MRZR-positive MS patients more frequently are female and show inflammatory changes of basic CSF parameters than MRZR-negative MS patients.