title: IL-27: a potential biomarker for responders to glatiramer acetate therapy.
abstract: 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.
authors.affiliation: Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Mindur
authors.affiliation: Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Reuben M
authors.initials: RM
authors.lastname: Valenzuela
authors.affiliation: Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Sudhir K
authors.initials: SK
authors.lastname: Yadav
authors.affiliation: Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Boppana
authors.affiliation: Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. Electronic address: jalbutsu@rwjms.rutgers.edu.
authors.forename: Suhayl
authors.initials: S
authors.lastname: Dhib-Jalbut
authors.affiliation: Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. Electronic address: itoko@rwjms.rutgers.edu.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ito
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D005260:Female; D000068717:Glatiramer Acetate / Q000494:pharmacology / Q000627:therapeutic use*; D057809:HEK293 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007378:Interleukins / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000188:drug therapy*; D011485:Protein Binding / Q000502:physiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D007378:Interleukins; C464565:MYDGF protein, human; D000068717:Glatiramer Acetate
keywords: Glatiramer acetate; IL-10; IL-27; Multiple sclerosis