Neutrophils Are Essential As A Source Of Il-17 In The Effector Phase Of Arthritis

<div><p>Objective</p><p>Th17 has been shown to have a pivotal role in the development of arthritis. However, the role of IL-17 in the T cell-independent effector phase has not fully been examined. We investigated whether IL-17 is involved in the effector phase of arthritis by using K/BxN serum-induced arthritis model.</p><p>Methods</p><p>K/BxN serum was transferred into IL-17 knockout (KO) mice, SCID mice and their control mice, and arthritis was evaluated over time. In order to clarify the source of IL-17 in the effector phase, neutrophils or CD4+ T cells collected from IL-17 KO or control mice were injected into IL-17 KO recipient mice together with K/BxN serum. To examine if neutrophils secrete IL-17 upon stimulation, neutrophils were stimulated with immune complex in vitro and IL-17 in the supernatant was measured by ELISA.</p><p>Results</p><p>K/BxN serum-induced arthritis was much less severe in IL-17 KO mice than in WT mice. Since K/BxN serum-transferred SCID mice developed severe arthritis with high serum IL-17 concentration, we speculated neutrophils are the responsible player as an IL-17 source. When wild type (WT) but not IL-17 KO neutrophils were co-injected with K/BxN serum into IL-17 KO mice, arthritis was exacerbated, whereas co-injection of WT CD4+ T cells had no effect. In vitro, stimulation of neutrophils with immune complexcaused IL-17 secretion.</p><p>Conclusions</p><p>Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. The trigger of secreting IL-17 from neutrophils may be immune complex.</p></div

Serological and Progression Differences of Joint Destruction in the Wrist and the Feet in Rheumatoid Arthritis - A Cross-Sectional Cohort Study - Fig 2

<p>(A) Comparison of joint destruction of the wrist and the feet in the duration of the disease. Larsen grade of the feet was significantly higher than that of the wrist in the first subgroup (p<0.001). (B) Comparison of difference of the joint destruction between the wrist and the feet in Larsen grade. <i>P</i> < 0.001.</p

Serological and Progression Differences of Joint Destruction in the Wrist and the Feet in Rheumatoid Arthritis - A Cross-Sectional Cohort Study

<div><p>Objective</p><p>To investigate clinical and radiological differences between joint destruction in the wrist and the feet in patients with RA.</p><p>Methods</p><p>A cross-sectional clinical study was conducted in an RA cohort at a single institution. Clinical data included age, sex and duration of disease. Laboratory data included sero-positivity for anti-cyclic citrullinated peptide (CCP) antibody and RF. Radiological measurements included Larsen grades and the modified Sharp/van der Heijde method (SHS) for the hands/wrists and the feet. Statistical analyses were performed using the Kruskal—Wallis H-test, a dummy variable linear regression model and multivariate logistic regression analysis with 95% confidence interval and odds ratios.</p><p>Results</p><p>A total of 405 patients were enrolled, and 314 patients were analysed in this study. The duration of disease in the foot-dominant group was significantly less than that in the wrist-dominant group. When patients were subdivided by duration of disease, the Larsen grade of the feet was significantly higher than that of the wrist in the first quadrant subgroup, but this was reversed with increasing duration of disease. Anti-CCP status was a significant predictive factor for joint destruction in the wrist but not in the feet, while RF status was not predictive in either the wrist or the feet.</p><p>Conclusions</p><p>Joint destruction in the feet started earlier than in the wrist, but the latter progresses faster with increasing duration of disease. Anti-CCP status predicts joint destruction in the wrist better than in the feet.</p></div

<i>ZNF257</i> gene structure and expression changes in inversion carriers.

<p><b>A.</b> The two most reliable transcripts of gene <i>ZNF257</i> are represented as dark and light-colored boxes corresponding to coding and non-coding exons, with their sizes and encoded proteins shown to the right. The longer transcript includes an extra 121-bp alternative non-coding exon in its 5’ UTR and in theory encodes a 32-aa shorter protein because of the shift in the methionine (Met) used as translation initiation from the three last nucleotides of the first exon to the third exon, common to both isoforms. The position of BP2 is indicated by a vertical arrow. A diagram of the longest protein domains (UniProt Q9Y2Q1) is represented by boxes below: green for the <i>Krüppel</i>-associated box (KRAB) domain, yellow for C2H2-type zinc fingers, and grey for degenerate zinc finger structures. <b>B.</b> Box plots of qPCR expression levels for <i>ZNF257</i> and the seven genes with significant or marginally significant differences between LCLs of 15 <i>Std</i>/<i>Std</i> (dark blue) and 11 <i>Std</i>/<i>Inv</i> (light blue) individuals. For each gene, expression values have been normalized by the average of <i>Std</i>/<i>Std</i> individuals, with every sample represented by grey points and outliers by open circles. Horizontal black lines within each box indicate median values. *, <i>P</i> < 0.05; ***, <i>P</i> < 0.001.</p

Demographic data.

<p><i>DAS28;</i> Disease Activity Score 28, <i>ESR;</i> erythrocyte sedimentation rate, <i>anti-CCP;</i> anti-cyclic citrullinated peptide antibody, <i>CRP;</i> C-reactive protein, <i>RF;</i> rheumatoid factor, <i>MMP-3;</i> matrix metalloprotenase-3, <i>HAQ;</i> health assessment questionnaire, <i>bDMARDs;</i> biological disease modifying anti-rheumatic drugs, <i>MTX;</i> methotrexate</p><p>Demographic data.</p

Inverse Association between Air Pressure and Rheumatoid Arthritis Synovitis

<div><p>Rheumatoid arthritis (RA) is a bone destructive autoimmune disease. Many patients with RA recognize fluctuations of their joint synovitis according to changes of air pressure, but the correlations between them have never been addressed in large-scale association studies. To address this point we recruited large-scale assessments of RA activity in a Japanese population, and performed an association analysis. Here, a total of 23,064 assessments of RA activity from 2,131 patients were obtained from the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Detailed correlations between air pressure and joint swelling or tenderness were analyzed separately for each of the 326 patients with more than 20 assessments to regulate intra-patient correlations. Association studies were also performed for seven consecutive days to identify the strongest correlations. Standardized multiple linear regression analysis was performed to evaluate independent influences from other meteorological factors. As a result, components of composite measures for RA disease activity revealed suggestive negative associations with air pressure. The 326 patients displayed significant negative mean correlations between air pressure and swellings or the sum of swellings and tenderness (p = 0.00068 and 0.00011, respectively). Among the seven consecutive days, the most significant mean negative correlations were observed for air pressure three days before evaluations of RA synovitis (p = 1.7×10⁻⁷, 0.00027, and 8.3×10⁻⁸, for swellings, tenderness and the sum of them, respectively). Standardized multiple linear regression analysis revealed these associations were independent from humidity and temperature. Our findings suggest that air pressure is inversely associated with synovitis in patients with RA.</p></div

Additional file 1: Supplement 1. of A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production

Correlations of the plasma concentration of IL-12p40 with those of IL-12p70 and IL-23. a The plasma concentration of IL-12p40 was correlated with that of IL-12p70 (rho = 0.33, p = 0.027). b There were no correlation between the plasma concentrations of IL-12p40 and IL-23. Supplement 2. Correlation between the proportion of CXCR3+ cells among CD3+CD4+ cells and the dose of glucocorticoids. The proportion of CXCR3+ cells among CD3+CD4+ cells was negatively correlated with the dose of glucocorticoids (rho = − 0.63 and p < 0.01). Statistical analysis was performed using Spearman’s rank correlation coefficient. (DOCX 34 kb

Evolutionary history of HsInv0379 inversion.

<p>Distribution of expected frequencies for a mutation arising 43,450 years ago under a model of human demography and different evolutionary scenarios according to forward-in-time simulations. Violin plots show the allele frequencies in 1,000 simulations for each selection coefficient (N_es between -30 and +10). The vertical solid line corresponds to the average frequency of the inversion in East Asia (4.73%) and dotted lines mark the range of frequencies observed in actual East Asian populations (2.4–8%). The likelihood of each N_es value (probability to obtain the observed frequencies) is shown at the right of the graph.</p

Comparison of 4 subgroups based on wrist/foot differences of joint destruction in Larsen grade.

<p><i>DAS28;</i> Disease Activity Score 28, <i>ESR;</i> erythrocyte sedimentation rate, <i>HAQ;</i> health assessment questionnaire, <i>anti-CCP;</i> anti-cyclic citrulinated peptide antibody, <i>RF;</i> rheumatoid factor, <i>bDMARDs;</i> biological disease modifying anti-rheumatic drugs, <i>MTX;</i> methotrexate.</p><p>*: statistically significant against Wrist-Foot group (p<0.05),</p><p>^§; statistically significant against Wrist group,</p><p>^†; statistically significant against Foot group, n.s. denotes not significant.</p><p>Comparison of 4 subgroups based on wrist/foot differences of joint destruction in Larsen grade.</p

Prognostic factors of the joint destruction in Larsen grade and covariables (OR, 95%CI).

<p><i>OR;</i> odds ratio, <i>95%CI;</i> 95% confidence interval, <i>DAS28;</i> Disease Activity Score 28, <i>anti-CCP;</i> anti-cyclic citrulinated peptide antibody, <i>RF;</i> rheumatoid factor,</p><p>*: p<0.05</p><p>Prognostic factors of the joint destruction in Larsen grade and covariables (OR, 95%CI).</p