Intensity of Intrathecal Total IgG Synthesis in Multiple Sclerosis Correlates with the Degree of Pleocytosis, Diversity of Intrathecal Antiviral Antibody Specificities, and Female Sex
Benjamin Vlad,
Marc Hilty,
Stephan Neidhart,
Klara Asplund Högelin,
Mario Ziegler,
Mohsen Khademi,
Andreas Lutterotti,
Axel Regeniter,
Roland Martin,
Faiez Al Nimer,
Ilijas Jelcic
Affiliations
Benjamin Vlad
Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland
Marc Hilty
Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland
Stephan Neidhart
Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland
Klara Asplund Högelin
Center for Molecular Medicine, Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden
Mario Ziegler
Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland
Mohsen Khademi
Center for Molecular Medicine, Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden
Andreas Lutterotti
Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland
Axel Regeniter
Infectious Disease Serology and Immunology, Medica Medizinische Laboratorien Dr. F. Kaeppeli AG, 8032 Zurich, Switzerland
Roland Martin
Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland
Faiez Al Nimer
Center for Molecular Medicine, Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden
Ilijas Jelcic
Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland
Background: The presence of intrathecal total IgG production is a hallmark of cerebrospinal fluid (CSF) characteristics in multiple sclerosis (MS). Herein, we systematically analyze how the intensity (instead of mere presence) of intrathecal total IgG production relates to basic CSF parameters in MS. Methods: We retrospectively assessed clinical routine CSF findings from 390 therapy-naïve relapsing-remitting MS patients diagnosed according to 2017 revised McDonald criteria. The intensity of intrathecal total IgG synthesis according to Reiber’s formula was stratified and correlated to demographics, CSF white cell count (WCC), and diversity of MRZ reaction, defined as a polyspecific intrathecal production of IgG reactive against ≥2 of the 3 viruses; measles (M), rubella (R), and varicella zoster (Z) virus. Results: The higher intensity of intrathecal total IgG production significantly correlated with higher CSF WCC (Spearman’s ρ = 0.433, p p < 0.001). Female patients showed higher intensity of intrathecal total IgG production and higher prevalence of positive MRZ reaction than males. Conclusions: The intensity of intrathecal total IgG production correlates with the degree of CSF WCC and diversity of MRZ reaction in MS. As yet unidentified female sex-related factors increase the intensity and diversity of intrathecal IgG production in MS.
