Linn Persson1, Sonia Longhi2, Johanna Enarsson1, Oluf Andersen3, Sara Haghigi3, Staffan Nilsson4, Martin Lagging1, Maria Johansson1, Tomas Bergström5. 1. Section for Clinical Virology, Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Guldhedsgatan 10 B, 41264 Gothenburg, Sweden. 2. Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257, CNRS et Université Aix-Marseille, 13288 Marseille, France. 3. Section of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. 4. Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden. 5. Section for Clinical Virology, Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Guldhedsgatan 10 B, 41264 Gothenburg, Sweden. Electronic address: tomas.bergstrom@microbio.gu.se.
Abstract
BACKGROUND: Patients with multiple sclerosis (MS) and their healthy siblings with the MS oligoclonal bands (OCB) trait, (a hyperimmune condition in form of two or more CSF enriched OCBs) harbor in cerebrospinal fluid (CSF) and serum elevated immunoglobulin G (IgG) titers against measles crude whole-cell antigen. The underlying mechanism resulting in the increased IgG antibody reactivity to measles remains unclear. The response may represent specific IgG reactivity to measles antigens or unspecific auto-antibodies targeting cellular components in the crude whole virus antigens commonly used in detection assays. OBJECTIVE: To determine the specificity of the measles IgG antibody reactivity by using a purified single nucleoprotein as antigen, thereby minimizing the contribution from auto-antibodies. STUDY DESIGN: The conserved N-terminal portion of the measles nucleocapsid protein (NCORE) was expressed as a specific antigen devoid of human or primate components. Serological analyses were performed on CSF and sera from MS patients, their clinically healthy siblings and healthy unrelated controls. RESULTS: MS patients demonstrated higher IgG reactivity compared to healthy controls in both CSF (P<0.001) and serum (P<0.001), and compared to siblings in CSF (P<0.001) and serum (P=0.2). Siblings with MS OCB trait showed higher IgG reactivity than healthy controls in CSF (P=0.002) and serum (P=0.01). Comparison between siblings with MS OCB trait and siblings without MS OCB trait showed (P=0.04) for CSF and (P=0.08) for serum. CONCLUSION: These findings suggest a measles-specific component in the antibody reactivity demonstrated by MS patients and their siblings with the MS OCB trait.
BACKGROUND:Patients with multiple sclerosis (MS) and their healthy siblings with the MS oligoclonal bands (OCB) trait, (a hyperimmune condition in form of two or more CSF enriched OCBs) harbor in cerebrospinal fluid (CSF) and serum elevated immunoglobulin G (IgG) titers against measles crude whole-cell antigen. The underlying mechanism resulting in the increased IgG antibody reactivity to measles remains unclear. The response may represent specific IgG reactivity to measles antigens or unspecific auto-antibodies targeting cellular components in the crude whole virus antigens commonly used in detection assays. OBJECTIVE: To determine the specificity of the measles IgG antibody reactivity by using a purified single nucleoprotein as antigen, thereby minimizing the contribution from auto-antibodies. STUDY DESIGN: The conserved N-terminal portion of the measles nucleocapsid protein (NCORE) was expressed as a specific antigen devoid of human or primate components. Serological analyses were performed on CSF and sera from MS patients, their clinically healthy siblings and healthy unrelated controls. RESULTS: MS patients demonstrated higher IgG reactivity compared to healthy controls in both CSF (P<0.001) and serum (P<0.001), and compared to siblings in CSF (P<0.001) and serum (P=0.2). Siblings with MS OCB trait showed higher IgG reactivity than healthy controls in CSF (P=0.002) and serum (P=0.01). Comparison between siblings with MS OCB trait and siblings without MS OCB trait showed (P=0.04) for CSF and (P=0.08) for serum. CONCLUSION: These findings suggest a measles-specific component in the antibody reactivity demonstrated by MS patients and their siblings with the MS OCB trait.
Authors: Linn Persson Berg; Marcus Eriksson; Sonia Longhi; Ingrid Kockum; Clemens Warnke; Elisabeth Thomsson; Malin Bäckström; Tomas Olsson; Anna Fogdell-Hahn; Tomas Bergström Journal: BMJ Neurol Open Date: 2022-07-27