IL-27: a potential biomarker for responders to glatiramer acetate therapy
| Autor: | Kouichi Ito, John E. Mindur, Sudhir K. Yadav, Reuben M. Valenzuela, Sridhar Boppana, Suhayl Dhib-Jalbut |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Immunology Pharmacology Peripheral blood mononuclear cell 03 medical and health sciences Young Adult Multiple Sclerosis Relapsing-Remitting medicine Immunology and Allergy Humans Glatiramer acetate Receptor Cells Cultured business.industry Multiple sclerosis Interleukins Interleukin EBI3 Glatiramer Acetate Middle Aged medicine.disease Interleukin 10 030104 developmental biology HEK293 Cells Treatment Outcome Neurology Leukocytes Mononuclear Biomarker (medicine) Female Neurology (clinical) business Biomarkers Immunosuppressive Agents medicine.drug Protein Binding |
| Zdroj: | Journal of neuroimmunology. 304 |
| ISSN: | 1872-8421 |
| Popis: | Glatiramer acetate (GA) is an FDA-approved efficacious drug for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, this treatment is not effective for all RRMS patients. Therefore, it is important to identify reliable biomarkers that can predict a beneficial clinical response to GA therapy. Since an increase in IL-27 has been demonstrated to suppress autoimmune and allergic diseases of inflammatory origin, we examined the effect of GA on the production of IL-27. We observed that IL-27 production in PBMCs cultured with GA was heterogeneous amongst MS patients and healthy donors (HD), and thus, defined these MS patients as either efficient, weak, or non-IL-27 producers. Interestingly, GA could induce the expression of the IL-27p28 subunit more efficiently than the IL-27 EBI3 subunit, and the production of IL-27 depended on MHC class II binding by GA. In addition, we found that GA could augment Toll-like receptor (TLR)-mediated IL-27 production. Importantly, serum production of IL-27 and IL-10 was significantly increased at 6months during GA therapy in clinical responders to GA, but not in GA non-responders. Altogether, our data suggest that GA-induced IL-27 may represent a therapeutic mechanism of GA-mediated immunomodulation and that GA-mediated IL-27 production in PBMCs is worth exploring as a biomarker to screen for GA responders prior to the initiation of GA treatment. |
| Databáze: | OpenAIRE |
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