title: Characterization of serum interleukin-15 in healthy volunteers and patients with early arthritis to assess its potential use as a biomarker.
abstract: As interleukin-15 (IL-15) has been implicated in the pathophysiology of rheumatoid arthritis, we analysed the serum IL-15 (sIL-15) levels in healthy subjects and patients with early arthritis to establish a cut-off point that might serve to define elevated sIL-15. This is an initial step to determine whether sIL-15 has the potential for use as a biomarker for patients with early arthritis. The IL-15 concentration was measured in serum obtained from 161 healthy controls and from 174 patients with early arthritis, and the relationship between the expression of the two IL-15 mRNA variants and the sIL-15 levels was also assessed. In healthy controls, the median sIL-15 value was 0.83 [interquartile range (IQR) 0-8.68] pg/mL; there was no significant difference in the sIL-15 values according to gender [median level in males was 1.99 (IQR: 0-8.68) pg/mL and in females 0.50 (0-8.25) pg/mL: p = 0.821]. Moreover, sIL-15 levels did not correlate with age (r = 0.033, p = 0.685), and they did not display a clear circadian rhythm in healthy donors, with the median values for IL-15 close to zero at each time tested. In the light of these findings, we considered that sIL-15 was elevated if its concentration was above 20 pg/mL, since this cut-off point corresponded to the 90th percentile for this healthy population. We found that 30% of the patients with early arthritis had sIL-15 values > 20 pg/mL. The levels of sIL-15 did not correlate with disease duration in early arthritis patients, nor did they fluctuate with changes in disease activity over the follow-up period. In addition, the high level of sIL15 in patients was not associated with alterations in the alternative splicing of the IL-15 mRNA, favouring the variant that produces the protein with a long signal peptide for secretion. Serum IL-15 levels were increased in a subpopulation of patients with early arthritis, indicating that this measure may serve as a biomarker for this condition. Further studies will be necessary to determine whether the clinical evolution or response to treatment of patients with high sIL-15 levels differs.
authors.affiliation: Rheumatology Service, Hospital Universitario La Princesa, IIS La Princesa, Madrid, Spain.
authors.forename: Amalia
authors.initials: A
authors.lastname: Lamana
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ortiz
authors.forename: José M
authors.initials: JM
authors.lastname: Alvaro-Gracia
authors.forename: Belén
authors.initials: B
authors.lastname: Díaz-Sánchez
authors.forename: Jesús
authors.initials: J
authors.lastname: Novalbos
authors.forename: Rosario
authors.initials: R
authors.lastname: García-Vicuña
authors.forename: Isidoro
authors.initials: I
authors.lastname: González-Alvaro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001168:Arthritis / Q000097:blood*; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood*; D002940:Circadian Rhythm; D017931:DNA Primers; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019409:Interleukin-15 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D019409:Interleukin-15; D012333:RNA, Messenger