GEE analysis in responders versus non-responders during treatment (adjusted for age, gender and time cofactors).

<p>*p<0.05, statistically significant.</p><p>R: responders; N:non- responders; CRP = C-reactive protein; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; TG = triglycerides.</p

GEE analysis in responders versus non-responders during treatment (no adjust cofactor).

<p>*p<0.05, statistically significant.</p><p>R: responders; N: non- responders; CRP = C-reactive protein; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; TG = triglycerides.</p

Baseline characteristics and treatment of patients with diagnosed JIA, stratified by their disease activity at 12 months^*.

<p>*Values are mean±SD, or number (%).</p><p>JIA = juvenile idiopathic arthritis; RF = rheumatoid factor; ANA = antinuclear antibodies; LAR =  International League of Associations for Rheumatology.</p><p>NSAID = Non-steroidal anti-inflammatory drug.</p

The change of inflammation marker and lipid profiles of JIA patients after etanercept treatment.

<p>(A) CRP (B) TG level significantly decreased after etanercept treatment in the inactive patients than active patient.(C) HDL-C (D) LDL-C (E) T-Chol, and (F) T-Chol/HDL-C ratio significantly increased after etanercept treatment in the inactive patients than active patient. CRP = C-reactive protein; TG = triglycerides; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; T-Chol  = total cholesterol</p

Lipid profile and blood dynamic changes in non-responders.

<p>The p values were tested by paired-sample t test and nonparametric test. All the p values were tested with values from before etanercept treatment; CRP = C-reactive protein; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; TG = triglycerides.</p

Additional file 1 of Incomplete penetrance of NOD2 C483W mutation underlining Blau syndrome

Additional file 1: Supplementary materials

Activating and inhibitory receptors on natural killer cells in patients with systemic lupus erythematosis-regulation with interleukin-15

<div><p>Natural killer (NK) cells may play an important role in the pathogenesis of SLE. Interleukin(IL)-15, an NK-enhancing cytokine, is over-expressed in SLE patients. In the present study, we examined the effect of IL-15 on NK cytotoxicity of SLE patients, and the expression of various activating and inhibitory NK receptors on NK cells from SLE patients in relation to disease activity. We also sought to determine how IL-15 would affect the NK receptor expression on NK cells from SLE patients. PBMCs were collected from 88 SLE patients with inactive disease activity (SLEDAI score<6) and active disease activity (SLEDAI score≥6), 26 age-matched healthy adults were used as controls. PBMC were incubated in the presence or absence of IL-15 (10ng/ml) for eighteen hours. CD3^-CD56⁺ lymphoctes were gated using flow cytometry and further divided into CD56^dim and CD56^bright subsets according to the MFI of CD56. We observed that 1. Serum IL-15 was elevated in SLE patients, and higher in active disease than in inactive disease; 2. NK cytotoxicity of SLE patients was deficient compared to controls and showed an impaired response to IL-15 compared to controls; 3.CD69, CD94, NKG2A, NKp30, and CD158b on NK cells from SLE patients were higher than controls, and could be further enhanced by IL-15; 4. NKp46 expression from SLE patients was higher than controls, but down-regulated by IL-15; 5.Deficient NKG2D and NKAT-2 expression were found on NK cells from SLE patients, which were enhanced by IL-15; 6. A unique NKp46^- subset and CD158b⁺ subsets were observed in NK cells from SLE patients but not controls. 7. Unlike controls, CD158k on NK cells from SLE patients failed to respond to IL-15. Taken together, we demonstrated the aberrant NCR and iNKR expression on NK cells and their distinct response to IL-15 in SLE patients. As IL-15 predominantly aggravates the aberrant NKR expression found in SLE, IL-15 antagonist may have therapeutic benefits in SLE patients.</p></div

Effect of interleukin(IL)-15 on NKAT2 expression of CD56⁺CD3^- NK cells from SLE and healthy control.

<p>A. Representative histograms of SLE patients (SLE) and controls(Normal) B.Comparison between SLE patients as a whole and controls (Normal) using scattergrams (transverse lines indicate means); C. Comparison between SLE patients with active disease and inactive disease; D. Comparison of NKAT2 expression on CD56^dim NK subsets in SLE patients with different severity as well as normal controls; E. Comparison of NKAT2 expression on CD56^bright NK subsets in SLE patients with different severity as well as normal controls. PBMC were stimulated with or without IL-15 (10ng/ml) for 18hrs. For C,D,E, data was expressed as mean percent expression (%) ± S.E.M. (Normal, n = 19; SLE, total n = 46, SLE with active disease, n = 27, SLE with inactive disease, n = 18) * p<0.05, ** p<0.01. The Wilcoxon signed rank test was applied for analysis of the difference of responses before and after IL-15 treatment. SLE patient and healthy control data were compared between groups using the Mann–Whitney U-test. (calculated by SPSS 17.0 software).</p

Effect of interleukin (IL)-15 on CD69 expression of CD56⁺CD3^- NK cells from SLE patients and healthy controls.

<p>A. Gating of CD56^birght and CD56^dim CD3^- NK cells by flow cytometry. B representative profile of Representative histograms of SLE patients (SLE) and controls (Normal); C. Comparison between SLE patients as a whole and normal controls (Normal) using scattergram (transverse lines indicate means); D. Comparison between SLE patients with active disease and inactive disease; E. Comparison of CD69 expression on CD56^dim NK subsets in SLE patients with different severity as well as normal controls; F. Comparison of CD69 expression on CD56^bright NK subsets in SLE patients with different severity as well as normal controls. PBMC were stimulated with or without IL-15 (10ng/ml) for 18hrs For D,E,F, data was expressed as mean percent expression (%) ± S.E.M. (Normal, n = 25; SLE, total n = 84, SLE with active disease, n = 44, SLE with inactive disease, n = 40) * p<0.05, ** p<0.01, The Wilcoxon signed rank test was applied for analysis of the difference of responses before and after IL-15 treatment. SLE patient and healthy control data were compared between groups using the Mann–Whitney U-test. (calculated by SPSS 17.0 software).</p

Effect of interleukin (IL)-15 on NKp46 expression of CD56⁺CD3^- NK cells from SLE patients and healthy control.

<p>A. Representative histograms of SLE patients (SLE) and controls(Normal); B. Comparison between SLE patients as a whole and controls (Normal) using scattergrams (transverse lines indicate means); C. Comparison between SLE patients with active disease and inactive disease; D. Comparison of NKp46 expression on CD56^dim NK subsets in SLE patients with different severity as well as normal controls; E. Comparison of NKp46 expression on CD56^bright NK subsets in SLE patients with different severity as well as normal controls. PBMC were stimulated with or without IL-15 (10ng/ml) for 18hrs For C,D,E, data was expressed as mean percent expression (%) ± S.E.M. (Normal, n = 19; SLE, total n = 47, SLE with active disease, n = 23, SLE with inactive disease, n = 24) * p<0.05, ** p<0.01, The Wilcoxon signed rank test was applied for analysis of the difference of responses before and after IL-15 treatment. SLE patient and healthy control data were compared between groups using the Mann–Whitney U-test. (calculated by SPSS 17.0 software).</p