Antibody cross-reactivity between casein and myelin-associated glycoprotein results in central nervous system demyelination
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 di...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 2, 2022
|
| In: |
Proceedings of the National Academy of Sciences of the United States of America
Year: 2022, Volume: 119, Issue: 10, Pages: 1-12 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.2117034119 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1073/pnas.2117034119 Verlag, kostenfrei, Volltext: http://www.pnas.org/doi/full/10.1073/pnas.2117034119 
|
| Author Notes: | 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 |
| Summary: | 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. |
|---|---|
| Item Description: | Gesehen am 09.04.2024 |
| Physical Description: | Online Resource |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.2117034119 |