Recombinant myelin oligodendrocyte glycoprotein quality modifies evolution of experimental autoimmune encephalitis in macaques
| Autor: | Ché Serguera, Jennifer Veth, Roger Le Grand, Julie Massonneau, Hugues Contamin, Joachim Confais, Emilie Avazeri, Claire-Maëlle Fovet, Lev Stimmer, Anke 't Jong, Philippe Horellou, Kumaran Deiva, Bert A. 't Hart, Audrey Perrin, Guylaine Miotello, Jeffrey J. Bajramovic, Jean Armengaud |
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| Rok vydání: | 2021 |
| Předmět: |
BACTERIAL PEPTIDOGLYCAN
Central nervous system ADJUVANT Biology Active immunization Pathology and Forensic Medicine Myelin oligodendrocyte glycoprotein White matter Pathogenesis C57BL/6 MICE 03 medical and health sciences Myelin 0302 clinical medicine Antigen medicine ENCEPHALOMYELITIS EAE BRAIN Molecular Biology 030304 developmental biology Autoimmune encephalitis 0303 health sciences INDUCTION MULTIPLE-SCLEROSIS Cell Biology 3. Good health MODEL PATHOLOGY medicine.anatomical_structure Immunology biology.protein SYSTEM 030217 neurology & neurosurgery |
| Zdroj: | Laboratory Investigation, 101(11), 1513-1522. SPRINGERNATURE |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/s41374-021-00646-x |
| Popis: | The authors describe quantitatively and qualitatively different forms of experimental autoimmune encephalitis (EAE) in cynomolgus macaques. They found that bacterial contaminants within recombinant human myelin oligodendrocyte glycoprotein seemed to aggravate disease evolution. They provide anatomopathological features of fulminant and progressive forms of EAE, allowing them to distinguish specific factors influencing the evolution of this model of autoimmune demyelinating disease.Experimental autoimmune encephalitis (EAE) is a well-recognized model for the study of human acquired demyelinating diseases (ADD), a group of inflammatory disorders of the central nervous system (CNS) characterized by inflammation, myelin loss, and neurological impairment of variable severity. In rodents, EAE is typically induced by active immunization with a combination of myelin-derived antigen and a strong adjuvant as complete Freund's adjuvant (CFA), containing components of the mycobacterial wall, while myelin antigen alone or associated with other bacterial components, as lipopolysaccharides (LPS), often fails to induce EAE. In contrast to this, EAE can be efficiently induced in non-human primates by immunization with the recombinant human myelin oligodendrocyte glycoprotein (rhMOG), produced in Escherichia coli (E. coli), purified and formulated with incomplete Freund's adjuvant (IFA), which lacks bacterial elements. Here, we provide evidence indicating how trace amounts of bacterial contaminants within rhMOG may influence the course and severity of EAE in the cynomolgus macaque immunized with rhMOG/IFA. The residual amount of E. coli contaminants, as detected with mass spectrometry within rhMOG protein stocks, were found to significantly modulate the severity of clinical, radiological, and histologic hallmarks of EAE in macaques. Indeed, animals receiving the purest rhMOG showed milder disease severity, increased numbers of remissions, and reduced brain damage. Histologically, these animals presented a wider diversity of lesion types, including changes in normal-appearing white matter and prephagocytic lesions. Non-human primates EAE model with milder histologic lesions reflect more accurately ADD and permits to study of the pathogenesis of disease initiation and progression. |
| Databáze: | OpenAIRE |
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