title: Interleukin 15 levels in serum may predict a severe disease course in patients with early arthritis.
abstract: BACKGROUND
  Interleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA).
  
  
  RESULTS
  Data from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (β Coefficient [95% confidence interval]: 0.12 [0.06-0.18]; p<0.001) or ACPA (0.34 [0.01-0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18-2.7; p = 0.007).
  
  
  CONCLUSIONS
  Patients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for patients that are candidates for early and more intensive treatment.
authors.affiliation: Rheumatology Service, Hospital Universitario de La Princesa, IIS Princesa, Madrid, Spain. isidoro.ga@ser.es
authors.forename: Isidoro
authors.initials: I
authors.lastname: González-Álvaro
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ortiz
authors.forename: José María
authors.initials: JM
authors.lastname: Alvaro-Gracia
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.forename: Belen
authors.initials: B
authors.lastname: Díaz-Sánchez
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Carvajal
authors.forename: J Alberto
authors.initials: JA
authors.lastname: García-Vadillo
authors.forename: Alicia
authors.initials: A
authors.lastname: Humbría
authors.forename: J Pedro
authors.initials: JP
authors.lastname: López-Bote
authors.forename: Esther
authors.initials: E
authors.lastname: Patiño
authors.forename: Eva G
authors.initials: EG
authors.lastname: Tomero
authors.forename: Esther F
authors.initials: EF
authors.lastname: Vicente
authors.forename: Pedro
authors.initials: P
authors.lastname: Sabando
authors.forename: Rosario
authors.initials: R
authors.lastname: García-Vicuña
mesh_terms: D000328:Adult; D017668:Age of Onset; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001168:Arthritis / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology*; D001323:Autoantibodies / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood; D012307:Risk Factors
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; C569274:IL15 protein, human; D019409:Interleukin-15; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor