Background Interleukin 6 (IL-6) has a crucial role in the pathogenesis of rheumatoid arthritis (RA) . Measurement of serum and plasma IL-6 level has been reported that is useful for monitoring of RA disease activity [2-3]. In contrast, it still take a few hours to measure serum IL-6 level using traditional methods, and cause limitation for measuring it as routine assessment in daily clinical setting.
Objectives We established high sensitivity IL-6 quick measure system. We investigated accuracy of the system in RA patients.
Methods Serum samples were collected from 70 patients fulfilling the ACR classification criteria for RA. Serum IL-6 levels can be measured by our current system using 100 μl whole blood in only 25 minutes. Measurement of serum IL-6 level by chemiluminescent enzyme immunoassay (CLEIA) employed a two-step sandwich method using a cartridge for IL-6 measurement developed specifically for the fully automated chemiluminescent enzyme immunoassay system (Lumipulse f, Fujirebio, Tokyo) used at our clinical laboratory. The lower detection limits for serum IL-6 were 5pg/ml in our system and 0.1pg/ml in CLEIA. We first examined the correlation between our system and CLEIA methods. Secondary, we compared both system IL-6 titers and clinical parameter (CRP, ESR, DAS28-CRP, DAS28-ESR, CDAI and SDAI). Pearson's correlation coefficients were used to assess whether the ranking of each IL-6 was similar between methods. Associations between clinical measures and serum IL-6 levels were assessed using Spearman's rank correlation test. A value of p<0.05 was considered statically significant.
Results Seventy patients were analyzed, and their mean age was 65.8 (18-83), 59 (84.3%) patients were female. 43 (61.4%) patients were used MTX and the mean dose was 7.44 mg/week. 18 (25.7%) patients were treated by biological agents (ETN: 10, IFX: 3, ABA: 3, ADA: 1). Figure 1 shows a correlation between the data measured by our system and CLEIA. The IL-6 level measured by our system positively correlated with IL-6 level measured by CLEIA. The correlation of our system (x) with CLEIA (y) for IL-6 was: y=0.895x-5.94, r=0.966 (p<0.0001). Serum IL-6 level in our system correlated significantly with CRP (r=0.497, P<0.001), ESR (r=0.478, P<0.001), DAS28-CRP (r=0.278, P<0.05) and DAS28-ESR (r=0.327, P<0.01), but did not correlate with CDAI (r=0.114, P=0.35) and SDAI (r=0.209, P=0.08). Serum IL-6 level in CLEIA correlated significantly with CRP (r=0.682, P<0.001), ESR (r=0.534, P<0.001), but did not correlate with DAS28-CRP (r=0.163, P=0.17), DAS28-ESR (r=0.229, P=0.06), CDAI (r=-0.034, P=0.78) and SDAI (r=0.089, P=0.46).
Conclusions Our cytokine quick measure system has accuracy as good as CLEIA methods. Serum IL-6 level can be measured in 25 minutes using our methods. It might be usable for daily clinical setting and contributes to RA treatment.
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Keiko Shimamoto, Tomoki Ito, Yoshio Ozaki et al. Serum Interleukin 6 before and after therapy with Tocilizumab is a principal biomarker in patients with rheumatoid arthritis. J Rheum 40(7):1074-81.
Disclosure of Interest K. Koyama: None declared, K. Matsuda Grant/research support: Toray, H. Haro: None declared