title: RGC-32 as a potential biomarker of relapse and response to treatment with glatiramer acetate in multiple sclerosis.
abstract: Currently there is critical need for the identification of reliable biomarkers to help guide clinical management of multiple sclerosis (MS) patients. We investigated the combined roles of Response Gene to Complement 32 (RGC-32), FasL, CDC2, AKT, and IL-21 as possible biomarkers of relapse and response to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2 years, a cohort of 15 GA-treated RRMS patients was clinically monitored and peripheral blood mononuclear cells (PBMCs) were collected at 0, 3, 6, and 12 months. Target gene mRNA expression was measured in patients' isolated PBMCs by real-time qRT-PCR. Compared to stable MS patients, those with acute relapses exhibited decreased expression of RGC-32 (p<0.0001) and FasL (p<0.0001), increased expression of IL-21 (p=0.04), but no change in CDC2 or AKT. Compared to non-responders, responders to GA treatment showed increased expression of RGC-32 (p<0.0001) and FasL (p<0.0001), and decreased expression of IL-21 (p=0.02). Receiver operating characteristic (ROC) analysis was used to assess the predictive accuracy of each putative biomarker. The probability of accurately detecting relapse was 90% for RGC-32, 88% for FasL, and 75% for IL-21. The probability of accurately detecting response to GA was 85% for RGC-32, 90% for FasL, and 85% for IL-21. Our data suggest that RGC-32, FasL, and IL-21 could serve as potential biomarkers for the detection of MS relapse and response to GA therapy.
authors.affiliation: Department of Neurology, University of Maryland, School of Medicine, United States.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Kruszewski
authors.affiliation: Department of Neurology, University of Maryland, School of Medicine, United States.
authors.forename: Gautam
authors.initials: G
authors.lastname: Rao
authors.affiliation: Department of Neurology, University of Maryland, School of Medicine, United States.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Tatomir
authors.affiliation: Department of Neurology, University of Maryland, School of Medicine, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hewes
authors.affiliation: Department of Neurology, University of Maryland, School of Medicine, United States; Research Service, Veterans Administration Maryland Health Care System, United States.
authors.forename: Cosmin A
authors.initials: CA
authors.lastname: Tegla
authors.affiliation: Department of Neurology, University of Maryland, School of Medicine, United States.
authors.forename: Cornelia D
authors.initials: CD
authors.lastname: Cudrici
authors.affiliation: Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland, School of Medicine, United States.
authors.forename: Vingh
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: Department of Neurology, University of Maryland, School of Medicine, United States; Veterans Administration Multiple Sclerosis Center of Excellence East, Baltimore, MD, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: Royal
authors.affiliation: Department of Neurology, University of Maryland, School of Medicine, United States; Research Service, Veterans Administration Maryland Health Care System, United States; Veterans Administration Multiple Sclerosis Center of Excellence East, Baltimore, MD, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Bever
authors.affiliation: Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland, School of Medicine, United States.
authors.forename: Violeta
authors.initials: V
authors.lastname: Rus
authors.affiliation: Department of Neurology, University of Maryland, School of Medicine, United States; Research Service, Veterans Administration Maryland Health Care System, United States; Veterans Administration Multiple Sclerosis Center of Excellence East, Baltimore, MD, USA. Electronic address: hrus@umaryland.edu.
authors.forename: Horea
authors.initials: H
authors.lastname: Rus
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D000068717:Glatiramer Acetate / Q000627:therapeutic use*; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D000098546:Interleukin-21
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins; D007378:Interleukins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C115049:RGCC protein, human; D000068717:Glatiramer Acetate; D000098546:Interleukin-21
keywords: Biomarker; FasL; Glatiramer acetate; IL-21; Multiple sclerosis; RGC-32