title: Killer-cell immunoglobulin-like receptor expression on lymphocyte subsets in multiple sclerosis patients treated with interferon-β: evaluation as biomarkers for clinical response.
abstract: BACKGROUND
  Both the adaptative and the innate immune systems interplay in multiple sclerosis (MS) pathogeny. Killer-cell immunoglobulin-like receptors (KIRs) are key regulators of the immune response, with activating and inhibitory isoforms.
  
  
  OBJECTIVE
  In this study we analysed whether the expression of KIR isoforms is implicated in MS pathogenesis and in the therapeutic response to interferon (IFN)-β.
  
  
  METHODS
  Peripheral blood samples were collected from 78 IFN-β-treated MS patients and 46 healthy controls (HC). KIR expression was evaluated by flow cytometry on natural killer (NK) and T cells.
  
  
  RESULTS
  The expression of KIRs on NK cells and T lymphocytes did not differ between MS patients and HC. IFN-β therapy decreased the expression of KIR2DL1/2DS1 and increased that of KIR2DL2/3 on NK cells. This therapy also reduced KIR2DL1/2DS1, KIR2DL2/2DL3 and KIR3DL2 expression on CD8(+) T cells. The baseline evaluation of the percentage of circulating CD16(+) NK cells was predictive of the clinical response to IFN-β; however, response to this therapy did not appear related to KIR expression.
  
  
  CONCLUSIONS
  This study shows that expression of KIR isoforms on NK and T lymphocytes correlated in different ways with IFN-β therapy, suggesting that KIR dynamics may be associated with the pathways involved in the mechanisms of action of IFN-β.
authors.affiliation: UGC Neurociencias Clínicas, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: García-León
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Gómez
authors.forename: Teresa
authors.initials: T
authors.lastname: Orpez-Zafra
authors.forename: Virginia
authors.initials: V
authors.lastname: Reyes-Garrido
authors.forename: Carmen
authors.initials: C
authors.lastname: Marín-Bañasco
authors.forename: Begoña
authors.initials: B
authors.lastname: Oliver-Martos
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández
authors.forename: Laura
authors.initials: L
authors.lastname: Leyva
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D011237:Predictive Value of Tests; D017452:Receptors, IgG / Q000276:immunology; D054340:Receptors, KIR / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007155:Immunologic Factors; D017452:Receptors, IgG; D054340:Receptors, KIR; D016899:Interferon-beta