title: Classification of individuals based on ex-vivo glatiramer acetate-induced interferon-γ and interleukin-4 response.
abstract: BACKGROUND
  Glatiramer acetate (GA) in multiple sclerosis acts through the induction of GA-specific T-helper 2 cells. Nevertheless, the phenomenon is not universal in patients, explaining individual differences in clinical response.
  
  
  OBJECTIVE
  The objective of this article was to categorize GA-treated patients.
  
  
  METHODS
  An enhanced quantitative PCR assay was used for measuring ex-vivo GA-induced IFNγ and IL4 mRNA responses in mononuclear cells from 23 healthy donors, 27 untreated patients, 33 short-term (≤6 months) and 77 long-term (>6 months) GA-treated patients. Thresholds for IFNγ and IL4 transcriptional response were calculated by ROC analysis and long-term treated patients were compared in terms of prognostic stratification.
  
  
  RESULTS
  Thresholds for IFNγ and IL4 transcriptional response were calculated at 5.36 and 1.41 relative expression (RE). Finally, 67% of long-term treated patients scored above both response thresholds. These patients had a higher proportion of relapse-free subjects (74% vs 40% when compare to patients who scored below both thresholds) and a significantly better relapse-free survival rate (p=0.006; CI 0.29-0.75). The negative predictive value to predict adverse clinical outcome was 79% (CI 0.63-0.90), meaning that by a positive response, there is a 79% chance that the patient will not experience a negative outcome at 3 years.
  
  
  CONCLUSIONS
  Our enhanced quantitative PCR assay produced clinically significant results for GA-treated patients. As such, if patients have a positive response, it means they have less chance of a relapse, while patients with a negative response have a greater probability of a worse outcome.
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, University Hospital San Luigi Gonzaga, Orbassano, TO, Italy. francesca.gilli@fastwebnet.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Gilli
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Navone
authors.forename: Paola
authors.initials: P
authors.lastname: Valentino
authors.forename: Letizia
authors.initials: L
authors.lastname: Granieri
authors.forename: Simona
authors.initials: S
authors.lastname: Perga
authors.forename: Simona
authors.initials: S
authors.lastname: Malucchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D015847:Interleukin-4 / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000145:classification* / Q000188:drug therapy* / Q000276:immunology*; D010455:Peptides / Q000627:therapeutic use; D016133:Polymerase Chain Reaction / Q000379:methods; D012372:ROC Curve; D055815:Young Adult
chemical_list: C508598:IL4 protein, human; D007166:Immunosuppressive Agents; D010455:Peptides; D015847:Interleukin-4; D000068717:Glatiramer Acetate; D007371:Interferon-gamma