Antibody cross-reactivity between casein and myelin-associated glycoprotein results in central nervous system demyelination

• Verfasst von: Chunder, Rittika [VerfasserIn]
• Verfasst von: Weier, Alicia [VerfasserIn]
• Verfasst von: Mäurer, Hannah [VerfasserIn]
• Verfasst von: Luber, Nicolas [VerfasserIn]
• Verfasst von: Enders, Michael [VerfasserIn]
• Verfasst von: Luber, Gabriele [VerfasserIn]
• Verfasst von: Heider, Thorsten [VerfasserIn]
• Verfasst von: Spitzer, Alfred [VerfasserIn]
• Verfasst von: Tacke, Sabine [VerfasserIn]
• Verfasst von: Becker-Gotot, Janine [VerfasserIn]
• Verfasst von: Kurts, Christian [VerfasserIn]
• Verfasst von: Iyer, Radhika [VerfasserIn]
• Verfasst von: Ho, Peggy P. [VerfasserIn]
• Verfasst von: Robinson, William H. [VerfasserIn]
• Verfasst von: Lanz, Tobias [VerfasserIn]
• Verfasst von: Kuerten, Stefanie [VerfasserIn]
• Titel: Antibody cross-reactivity between casein and myelin-associated glycoprotein results in central nervous system demyelination
• Verf.angabe: Rittika Chunder, Alicia Weier, Hannah Mäurer, Nicolas Luber, Michael Enders, Gabriele Luber, Thorsten Heider, Alfred Spitzer, Sabine Tacke, Janine Becker-Gotot, Christian Kurts, Radhika Iyer, Peggy P. Ho, William H. Robinson, Tobias V. Lanz, and Stefanie Kuerten
• E-Jahr: 2022
• Jahr: March 2, 2022
• Umfang: 12 S.
• Fussnoten: Gesehen am 09.04.2024
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2022
• Band/Heft Quelle: 119(2022), 10, Artikel-ID e2117034119, Seite 1-12
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.2117034119
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1885387911

Abstract

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease of the central nervous system (CNS) with a high socioeconomic relevance. The pathophysiology of MS, which is both complex and incompletely understood, is believed to be influenced by various environmental determinants, including diet. Since the 1990s, a correlation between the consumption of bovine milk products and MS prevalence has been debated. Here, we show that C57BL/6 mice immunized with bovine casein developed severe spinal cord pathology, in particular, demyelination, which was associated with the deposition of immunoglobulin G. Furthermore, we observed binding of serum from casein-immunized mice to mouse oligodendrocytes in CNS tissue sections and in culture where casein-specific antibodies induced complement-dependent pathology. We subsequently identified myelin-associated glycoprotein (MAG) as a cross-reactive antigenic target. The results obtained from the mouse model were complemented by clinical data showing that serum samples from patients with MS contained significantly higher B cell and antibody reactivity to bovine casein than those from patients with other neurologic diseases. This reactivity correlated with the B cell response to a mixture of CNS antigens and could again be attributed to MAG reactivity. While we acknowledge disease heterogeneity among individuals with MS, we believe that consumption of cow’s milk in a subset of patients with MS who have experienced a previous loss of tolerance to bovine casein may aggravate the disease. Our data suggest that patients with antibodies to bovine casein might benefit from restricting dairy products from their diet.