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BackgroundEvaluation of monosodium urate (MSU) crystal deposition and related lesion in joints using ultrasound in gout and hyperuricemia patients. MethodsTotal 202 gout patients and 43 asymptomatic hyperuricemia patients were included, the clinical data and ultrasunic assessment results were collected and statistically analyzed. ResultsDeposition of MSU crystals were found in 25.58% (11/43) of the patients with asymptomatic hyperuricemia and 76.24% (154/202) of the patients with gout. In the all examined 1082 joints from gout patients, 33.09% (358/1082) of them were detected MSU crystals. In MSU crystal positive joints, 77.37% (277/358) of them had history of attacks. Among the joints of gouty arthritis, 56.88% (277/487) of them were found MSU crystals. Double contour sign (DCS), hyperechoic aggregate (HAG) and Tophi were found in 32.65% (159/487), 7.80% (38/487) and 24.64% (120/487) of the joints, respectively. DCS and Tophi, but not HAG, appeared increasingly in gout duration extension. In the patients with more than 15 years of gout history, DCS, Tophi and HAG were found in 48.18%, 40.00%, 6.36% of US assessed joints, respectively. In the gout patients, synovial lesion and bone erosion were found in 17.74% (192/1082) and 7.58% (82/1082) of joints, respectively. Synovial lesion was related with HAG, while bone erosion was related to tophi and DCS. Nephrolithiasis was detected in 20.30% (41/202) of gout patients and 4.65% (2/43) of hyperuricemia patients, indicating nephrolithiasis occurred in more gout patients than in hyperuricemia patients.ConclusionHAG is the early sign of MSU crystal deposition in joints. Early urate lowering therapy (ULT) may reduce HAG and ameliorate synovitis and synovial hypertrophy. DCS and tophi are the risk factors of bone erosion. Early ULT should be considered in the gout patients with DCS or tophi. And nephrolithiasis was remarkably relevant to MSU crystal deposition in joints in gout patients.

s Background Ultrasound is a useful tool to evaluate and quantify skin lesions. Few studies have assessed the criterion validity of skin ultrasound in systemic sclerosis (SSc). The aims of the study were to investigate skin thickness and stiffness using ultrasound and shear wave elastography (SWE) in SSc and to validate skin ultrasound measurements against histological skin thickness. Methods A total of 22 patients with diffuse cutaneous SSc (dcSSc), 22 with limited cutaneous SSc (lcSSc), and 22 age- and gender-matched healthy controls were enrolled. Skin thickness and stiffness were measured by B-mode ultrasound with SWE imaging on the bilateral fingers and hands. Additional ultrasound evaluation was carried out in 13 patients (9 dcSSc and 4 lcSSc) on their dorsal forearms, followed by skin biopsy conducted in the same skin areas. Correlations between ultrasound measurements and histological skin thickness and modified Rodnan skin score (mRSS) were investigated using Spearman’s correlation. Results Compared with controls, ultrasound-measured skin thickness and skin stiffness were significantly higher in patients with SSc (p r = 0.6926, p = 0.009). A weaker association was also observed between histological skin thickness and local mRSS (r = 0.5867, p = 0.050). Conclusions Ultrasound is a reliable tool for quantifying skin involvement in SSc. Ultrasound-measured skin thickness showed good agreement with histological skin thickness.

Additional file 1 : Supplementary Figure S1. Correlations between ultrasound measured skin thickness and skin stiffness. Supplementary Figure S2. Correlations between whole body mRSS and ultrasound parameters measured at fingers and hands.

AIMS To evaluate the fluctuation of serum uric acid (SUA) during acute gout (AG) and explore its potential mechanisms. METHODS Data such as SUA, urinary uric acid and 24-hour uric acid urinary excretion were collected from 126 patients diagnosed with gout and were analyzed. RESULTS Serum uric acid was negatively correlated with age in gout patients, and significantly elevated in patients aged ≤50 years. Twenty-four-hour uric acid urinary excretion was affected by SUA, creatinine clearance, age, body mass index and urine volume. In contrast, clearance of uric acid and fractional excretion of uric acid (FEur) were more stable. SUA was significantly downregulated during acute attacks. Of the AG patients, 34.92% had detected SUA

Background Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation and fibrosis. Our previous research has indicated that Sirtuin1 (Sirt1) plays a role in the regulation of TNF-α-induced inflammation; however, whether Sirt1 may inhibit the progress of SSc by blocking inflammation remains unknown. Objective We aimed to investigate the function of Sirt1 in SSc. Methods The function and its mechanism of Sirt1 were evaluated in fibroblasts or scleroderma mice. The expression of Sirt1 and cytokines was analyzed using real-time PCR, western blot, ELISA and immunohistochemistry. Results We determined that fibroblasts of SSc patients were activated to exhibit inflammation. Sirt1, activated by resveratrol (Res), ameliorated cutaneous inflammation and fibrosis in bleomycin (BLM)-induced scleroderma mice. An improvement in mammalian target of rapamycin (mTOR) was identified in the fibroblasts of SSc patients and the skin lesions of BLM mice. Rapamycin, an mTOR specific inhibitor, substantially inhibited the induced inflammation and fibrosis. The enhancement of mTOR expression in the skin lesions of the BLM-treated mice was significantly inhibited by Sirt1 activation. However, in both the BLM-treated cells and mice, Res exerted an inhibitory function on the expression of inflammatory factors, and collagen was diminished following mTOR knockdown. These findings suggest that Res may inhibit inflammation and fibrosis via mTOR. Conclusion The modulation of Sirt1 activity may represent a potential therapeutic method for SSc. The mechanism may involve the inhibition of mTOR phosphorylation, whereas mTOR activity was shown to be a pathogenic culprit of SSc.

Background Functional variants of the B cell gene, B cell scaffold protein with ankyrin repeats 1 (BANK1) contribute to rheumatoid arthritis (RA) susceptibility, but their influences on B cell responses are unclear. Moreover, the function of induced T regulatory cells (iTregs) in the inflammatory milieu in a collagen-induced arthritis (CIA) model is unknown. This study was performed to investigate the roles of BANK1 in CIA and the interaction between B cells and iTregs. Methods The changes in BANK1 mRNA and protein levels and their correlation with disease severity in CIA were determined. Next, the antigen-presenting function and autoantibody production in B cells were evaluated by co-culture with effector T cells and iTregs, respectively, both in vitro and in vivo. Then, the mechanisms underlying these interactions were studied by adding neutralizing antibodies or transwell inserts and by adoptive transfer to B-cell-depleted CIA mice. Results The BANK1 level decreased in the peripheral blood, spleen and lymph nodes of CIA mice, particularly during the acute stage of arthritis, and exhibited negative correlation with disease severity and autoantibody production. B cell responses were enhanced by this decrease. B cells from CIA mice (CIA-B cells) promoted iTreg differentiation, proliferation and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) expression. Meanwhile, BANK1 expression in CIA-B cells increased after co-culture with iTregs, limiting B cell responses. All these interactions depended on cell contact with CTLA-4-overexpressing iTregs but were independent of CTLA-4 cytokine. Conclusion Decreased BANK1 expression promotes B cell responses, resulting in an increased antigen presentation ability and autoantibody production that subsequently influences the communication between B cells and iTregs through a cell-contact-dependent and CTLA-4- cytokine-independent mechanism in CIA mice.

Gouty arthritis is characterized by inflammation induced by monosodium urate (MSU) crystal deposition, which is resulted by an increase of serum urate concentration. The management of gout, especially the recurrent acute attacks of chronic gouty arthritis, is still a problem to be resolved. In this study, we aimed to develop the preventive and therapeutic effect of resveratrol on gouty arthritis. MSU was used to induce gouty arthritis in the foot pad of C57BL/6 mice. Yeast polysaccharide and potassium oxonate were used to induce hyperuricemia in Kunming mice. Resveratrol was intraperitoneal injected to the mice in the treatment group. The pad inflammation and the level of serum uric acid were investigated to estimate the effect of resveratrol in gouty arthritis. Hyperuricemia was significantly detected in the mice treated with yeast polysaccharide and potassium oxonate, and gouty arthritis was successfully induced with MSU in mice. We further identified that resveratrol inhibited pad swelling and pad 99mTc uptake in gouty mice. Moreover, serum uric acid level was also decreased by resveratrol in hyperuricemia mice. This study highlighted that resveratrol might be applied to prevent the recurrent acute attack of gouty arthritis because of its inhibition of articular inflammation and down-regulation of serum uric acid.

Objectives: New interleukins (ILs), especially members of IL-1 and IL-12 families, have recently been reported to be involved in the development and regulation of autoimmune and inflammatory diseases. In this study, we aimed to explore the impact of these new ILs in psoriasis (Ps) and psoriatic arthritis (PsA). Methods: Forty PsA patients, 20 Ps patients, and 20 healthy controls (HCs) were recruited. Blood samples were obtained for detecting the levels of ILs, IL-12/23p40, and tumor necrosis factor α (TNF-α). The severity of skin lesions was assessed by the Psoriasis Area and Severity Index (PASI). Arthritis activities of PsA patients were assessed by the PsA Joint Activity Index. For PsA patients, circulating osteoclastogenesis-related cytokines (osteoprotegerin and receptor activator of nuclear factor-κB ligand) and numbers of osteoclast precursors were evaluated. Radiographic features of affected joints in these patients were scored for erosion, joint-space narrowing, osteolysis, and new bone formation. Correlations among levels of these ILs, Ps, and PsA disease activities and bone erosions were studied. Results: Ps and PsA patients had higher serum levels of TNF-α, IL-12/23p40, and IL-33. Serum levels of IL-34 and IL-35 were higher in PsA patients than in Ps patients and HCs. Patients with pustular Ps had higher serum levels of IL-36α and IL-38 than patients with Ps vulgaris or HCs. Increased serum levels of IL-36α were positively correlated with PASI. Conclusion: Certain ILs were elevated in the circulation of patients with Ps and PsA, which might contribute to the pathogenesis of skin lesions and arthritis.

Background To investigate whether monosodium urate (MSU) crystals induce interleukin (IL)-1β in human fibroblast-like synoviocytes (FLS), and whether the NLRP3 inflammasome is involved in the inflammatory mechanism. Methods Human FLS isolated from explants of synovial tissue were stimulated with MSU crystals (0.001 to 0.5 mg/ml) for different time course (6 hours to 48 hours). The expressions of IL-1β, IL-6, TNF-α and NLRP3 were evaluated with ELISA, Western blot and quantitative real-time PCR. Results Exposure of FLS to MSU crystals transiently induced a significant increase in IL-1β expression in culture medium with a peak at 6 h. The mRNA level of IL-1β in the FLS cells had a similar pattern at this time point. Changes in IL-6 and TNF-α expression were not observed. Simultaneously, intercellular pro-IL-1β was detected at 6 h. Furthermore, MSU crystals also induced NLRP3 mRNA and protein expression at 6 h to 48 h after MSU treatment. Conclusions MSU crystals directly increased IL-1β and intercellular NLRP3 expression in FLS cells. It is suggested that the NLRP3 inflammasome may be associated with IL-1β in FLS treated with MSU. Altogether, MSU could induce production and release of IL-1β through the NLRP3 inflammasome in human synoviocytes. Electronic supplementary material The online version of this article (doi:10.1186/s12950-015-0070-7) contains supplementary material, which is available to authorized users.

Multiple HLA-B alleles (haplotypes) are associated with drug-induced adverse responses and disease risks but are difficult to be directly genotyped. The goal of this study is to identify single nucleotide polymorphisms (SNPs) that are able to tag HLA-B alleles in the Chinese Han population. Twelve HLA-B alleles that are associated with drug adverse responses and disease risks were identified. They were sequenced initially in 880 Chinese Han subjects where high-density SNPs within the HLA-B gene were available. Performances of these SNPs to tag the HLA-B alleles were assessed primarily by sensitivity and specificity. Two HLA-B alleles can be reliably tagged by SNPs at 100% sensitivity and95% specificity. For example, HLA-B*15:02 can be tagged by the 'C' allele of rs10484555, and HLA-B*58:01 can be tagged by the 'T' allele of rs9262570. These results were confirmed in 500 additional Chinese Han subjects. If confirmed in independent studies, these tag SNPs could be used as a reliable, simple and cost-effective alternative for genotyping a subset of HLA-B alleles.

T follicular helper (Tfh) cells aid effector B cells, and augment autoimmunity, whereas the role of Tfh cells on regulatory B (Breg) cells in systemic lupus erythematosus (SLE) is not known. The aim of this study is to investigate the percentage of Breg cells in SLE, and the role of Tfh cells on Breg cells. First, we demonstrated the presence of Breg cells in SLE peripheral blood mononuclear cells and in involved skins. Both the percentage of circulating Breg cells and the ability to produce interleukin-10 (IL-10) were elevated in SLE patients. The percentage of Breg cells increased during SLE flares and decreased following disease remission. Second, Tfh cell expansion was not only related to autoantibody production but also correlated with the increased percentage of Breg cells. Third, in vitro studies revealed that Tfh cell-derived IL-21 could promote IL-10 production and Breg cell differentiation. In conclusions, these data imply that SLE flares may be linked to the expansion of Tfh cells and that Breg cells are increased in a regulatory feedback manner. Thus, SLE development may be associated with the complex regulation of Tfh cells and diverse B cell subsets.