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Background/Purpose The intergenic SNP rs10865331 at 2p15 was identified as a major risk factor for ankylosing spondylitis (AS) susceptibility in genome-wide association studies (GWAS). B3GNT2 gene regulates polylactosamine synthesis is potentially functionally relevant to AS disease development. We investigated whether SNP rs10865331 and two B3GNT2 SNPs (rs11900673 and rs1136151) are associated with AS susceptibility and disease severity in Taiwanese. Methods Distributions of genotypes, alleles, and haplotypes of three SNPs were compared between 1,472 AS patients and 2,117 healthy blood donors and among AS patients stratified by clinical characteristics. Results The intergenic SNP rs10865331 was significantly associated with AS (PFDR = 1.02E-05) in Taiwanese. In AS patients stratified by positivity of HLA-B27 and syndesmophyte formation, all three B3GNT2 locus SNPs (rs11900673, rs1136151, and rs10865331) were significantly associated with syndesmophyte formation among HLA-B27 positive AS patients. Haplotype analyses revealed that the “CTA” (rs11900673C/rs1136151T/rs10865331A) haplotype was significantly associated with AS susceptibility (Padj = 0.0177) and syndesmophyte formation (Padj = 0.016) in HLA-B27 positive patients. In contrast, “TCG” (rs11900673T/rs1136151C/rs10865331G) haplotype showed protection against AS development (Padj = 0.0005 for HLA-B27 positive and Padj = 0.004 for HLA-B27 negative, respectively) and syndesmophyte formation (Padj = 0.0017) in HLA-B27 positive patients. Furthermore, B3GNT2 mRNA expressions were negatively associated with erythrocyte sedimentation rate (ESR, P = 0.0103), C-reactive protein (CRP, P = 0.0353), Bath ankylosing spondylitis functional index (BASFI, P = 0.0171), and syndesmophyte formation (P = 0.0148). Conclusion Our data suggest that B3GNT2 gene may contribute to AS development and affect AS severity by interacting with HLA-B27 in Taiwanese.

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Particle morphology can affect the performance of an electrostatic precipitator air–liquid interface (ESP-ALI) cell exposure system and the resulting cell toxicity. In this study, three types of monodisperse aerosols – spherical sucrose particles, nonspherical align soot aggregates, and nanosilver aggregates/agglomerates – were selected to evaluate the collection efficiency at flow rates ranging from 0.3 to 1.5 lpm. To quantify the particle morphology, the fractal dimensions (Df) of the tested aerosols were characterized. The penetration of fine particles (dp = 100–250 nm) under different operating conditions was correlated with a characteristic exponential curve using the dimensionless drift velocity (Vc/Vavg,r) as the scaling parameter. For nanoparticles (NPs, dp nm) with different particle morphologies, the particle penetrations in the ESP-ALI were similar, but their diffusion losses were not negligible. In contrast, for fine particles, the collection efficiency of soot nanoaggregates (Df = 2.29) was higher than that of spherical sucrose particles. This difference might be due to the simultaneous influences of the electric field-induced and flow field-induced alignment. Furthermore, based on Zhibin and Guoquan’s Deutsch model, a quadratic equation was applied to fit the experimental data and to predict the performance of the ESP-ALI.

The polysaccharides from Ophiopogon japonicus (OJPs) were known to have protective effects against diabetes, and cardiovascular and chronic inflammatory diseases. However, OJPs were poorly absorbed after oral administration, resulting in limited efficacy because of the low bioavailability. In this study, OJPs extracted and fractionated from Ophiopogon japonicus were used to prepare OJPs/chitosan (CS)/whey protein (WP) co-assembled nanoparticles. The OJPs/CS/WP nanoparticles showed high biocompatibility and inhibited the cytotoxicity of RAW264.7 cells induced by nickel. With the assistance of CS and WP, the anti-inflammatory and antioxidant activities of OJPs were enhanced because the nanoparticles improved OJPs uptake by RAW264.7 macrophage cells as evidenced by efficient scavenging of DPPH and ABTS free radicals and effective inhibition of NO production and the gene expressions of iNOS, COX2, TNF-α, CCL2, and CXCL2 inflammatory signals. Determining the transepithelial electrical resistance and paracellular permeability of Caco-2 monolayer/macrophage co-cultured system suggested that the OJPs-loaded nanoparticles effectively protected the intestinal epithelial barrier integrity against the damage caused by LPS-stimulated macrophage inflammation and attenuated the defects of intestinal epithelial TJ barrier and permeability. These findings suggest that the OJPs/CS/WP nanoparticles may be potential carriers for oral delivery of OJPs to treat intestinal barrier defects, such as inflammatory bowel disease (IBD).

Ankylosing spondylitis (AS) is a chronic inflammatory disease that leads to spinal ankylosis. The receptor activator of the nuclear factor-kappa (RANK), RANK ligand, and osteoprotegerin (OPG) (RANK/RANKL/OPG) pathway plays critical roles in bone metabolism and the immune system. The current study was aimed at investigating whether six single-nucleotide polymorphisms (SNPs) within the RANK, RANKL, and OPG genes essential for bone homeostasis are associated with AS. Genotype distributions, allele and haplotype frequencies, were compared between 1120 AS patients and 1435 healthy controls and among AS patients with stratification by syndesmophyte formation, onset age, and HLA-B27 positivity. We found that RANKL SNPs were associated with AS syndesmophyte formation. Notably, the RANKL SNP haplotype rs7984870C/rs9533155G/rs9525641C was negatively associated with AS susceptibility and appeared to protect against syndesmophyte formation in AS. Functionally, RANKL promoter SNPs (rs9525641 C/T and rs9533155 G/C) affected DNA-protein complex formation and promoter activity in promoter reporter analyses. The OPG SNP haplotype rs2073618G/rs3102735T was significantly associated with HLA-B27 negativity in AS patients. Furthermore, AS patients with syndesmophyte formation had significantly lower levels of soluble RANKL levels than those without syndesmophyte formation. Our data suggested a role for RANKL in AS susceptibility and severity.

Background Type III interferons (IFNs) or IFN-λs are the newly discovered cytokines that primarily target the cells of epithelial and myeloid lineages, which are major components of kidneys. The current study aimed to investigate whether IFN-λs are involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis. Methods TaqMan allele discrimination assays were used to determine IFNL3/4 SNP genotypes of 1620 healthy controls and 1013 SLE patients (two independent cohorts consisting of 831 and 182 subjects, respectively) from Taiwan. The distributions of IFNL3/4 SNP genotypes and allele frequencies were compared between SLE patients and healthy controls and among SLE patients stratified by clinical phenotypes. ELISA was used to determine the serum IFN-λ3 concentrations of SLE patients. Results All major IFN3/4 SNP alleles were significantly associated with the risk for lupus nephritis (rs8099917T, PFDR = 0.0021, OR 1.75, 95% CI 1.24–2.47; rs12979860C, PFDR = 0.0034, OR 1.65, 95% CI 1.18–2.30; rs4803217C, PFDR = 0.0021, OR 1.76, 95% CI 1.25–2.48; and ss469415590TT, PFDR = 0.0021, OR 1.73, 95% CI 1.23–2.42) among SLE patients. Similarly, the major IFNL3/4 SNP haplotype rs8099917T-ss469415590TT-rs12979860C-rs4803217C (or T-TT-C-C) was a significant risk factor for lupus nephritis (P = 0.0015, OR 1.68, 95% CI 1.22–2.32). Additionally, all minor IFN3/4 SNP alleles were significantly associated with SLE susceptibility in nephritis-negative SLE patients as compared to normal healthy controls (rs8099917G, PFDR = 0.00177, OR 1.68, 95% CI 1.24–2.28; rs12979860T, PFDR = 0.00299, OR 1.58, 95% CI 1.18–2.32; rs4803217A, PFDR = 0.00176, OR 1.65, 95% CI 1.22–2.23; and ss469415590ΔG, PFDR = 0.00176, OR 1.70, 95% CI 1.26–2.29). Furthermore, the elevated serum levels of IFN-λ3 were significantly correlated with the complement depression and the high SLE disease activities in SLE patients. Conclusions IFN-λ3/4 genetic variants play a unique role in the development of lupus nephritis and SLE. Electronic supplementary material The online version of this article (10.1186/s13075-018-1683-z) contains supplementary material, which is available to authorized users.

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115, OR, 14.90, 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017, OR, 1.69, 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33, OR, 28.79, 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.

Table S1. Association of IFN3/4 locus SNP haplotypes (rs8099917-ss469415590-rs12979860-rs4803217) with lupus nephritis among SLE patients. Figure S1. Schematic illustration of IFNL3/4 locus SNP locations. Sizes of exons and distances between exons indicated as base pairs (bp). First exon (exon 1) of each gene starts from ATG start codon and last exon (exon 5) of each gene ends at stop codon. SNP rs8099917 located in IFNL4 promoter region (3945 bp upstream of translation starting site) and SNP rs4803217 in IFNL3 3′-UTR (52 bp downstream of translation termination codon). Two other SNPs (ss469415590 and rs12979860) are with IFNL4 gene. Figure S2. Pairwise LD patterns of four IFNL3/4 locus SNPs on chromosome 19 show coefficient of linkage disequilibrium D′ (red) and square of correlation coefficient between two indicator variables γ2 (black) of all subjects (A), SLE cases (B), and healthy controls (C), respectively. Darker colors indicate stronger LD. Figure S3. Association of IFN3 levels with SLE disease activity (SLEDAI) in replication cohort. A IFNL3 levels significantly (unpaired t test t = 3.783, P = 0.0003) increased in high SLEDAI SLE patients (SLEDAI ≥ 4, N = 40; IFNL3 concentration 8.450 ± 1.263 pg/ml) than in low SLEDAI patients (SLEDAI = 0, N = 40; IFNL3 concentration 3.260 ± 0.5365 pg/ml). B IFNL3 levels not significantly different (unpaired t test t = 1.650, P = 0.103) between nephritis-positive patients (N = 40; IFNL3 concentration 4.645 ± 1.039 pg/ml) and nephritis-negative patients (N = 40; IFNL3 concentration 7.065 ± 1.036 pg/ml). (DOCX 194 kb)

Background Biologic therapies are more effective but more costly than conventional therapies in treating psoriatic arthritis. Objectives To evaluate the cost-efficacy of etanercept, adalimumab and golimumab therapies in treating active psoriatic arthritis in a Taiwanese setting. Methods We conducted a meta-analysis of randomized placebo-controlled trials to calculate the incremental efficacy of etanercept, adalimumab and golimumab, respectively, in achieving Psoriatic Arthritis Response Criteria (PsARC) and a 20% improvement in the American College of Rheumatology score (ACR20). The base, best, and worst case incremental cost-effectiveness ratios (ICERs) for one subject to achieve PsARC and ACR20 were calculated. Results The annual ICER per PsARC responder were US$27 047 (best scenario US$16 619; worst scenario US$31 350), US$39 339 (best scenario US$31 846; worst scenario US$53 501) and US$27 085 (best scenario US$22 716; worst scenario US$33 534) for etanercept, adalimumab and golimumab, respectively. The annual ICER per ACR20 responder were US$27 588 (best scenario US$20 900; worst scenario US$41 800), US$39 339 (best scenario US$25 236; worst scenario US$83 595) and US$33 534 (best scenario US$27 616; worst scenario US$44 013) for etanercept, adalimumab and golimumab, respectively. Conclusions In a Taiwanese setting, etanercept had the lowest annual costs per PsARC and ACR20 responder, while adalimumab had the highest annual costs per PsARC and ACR responder.

Human leukocyte antigen (HLA) class I ligands and Killer immunoglobulin-like receptors (KIRs) regulate the cytolytic activity of natural killer (NK) cells and certain T cells. We examined their genetic predisposition to disease susceptibility and clinical phenotypes in Taiwanese ankylosing spondylitis (AS) patients. KIR genotyping and Human Leucocyte Antigen C (HLA-C) sequencing were performed in 653 Taiwanese AS patients and 952 healthy controls. KIR genotype distributions and HLA-C allele frequencies were compared in patients and controls and among patients with and without HLA-B27 positivity, early age onset and spinal syndesmophytes. HLA-C alleles were functionally characterized using 3D structural modelling with peptide simulation. This study discovered that the HLA-C*12:02:02 allele (43.42% vs. 3.31%; p < 0.00001 odds ratio (OR), 16.88; 95% confidence intervals (CI): 11.27–25.28) confers a strong risk for Taiwanese AS development. The 3D modelling results identified four unique amino acid polymorphisms, Ala73, Trp156, Arg219 and Met304, that may affect the function of the HLA-C*12:02:02 allele. KIR2DL5 (p = 0.0047; pFDR = 0.0423) and the KIR Bx haplotype (p = 0.0000275) were protective against Taiwanese AS, while KIR 2DS4/1D (22 base pair truncated deletion; p = 0.0044; pFDR = 0.1998) appeared to be a risk factor for it. KIR2DL5 combined with the HLA-C1/C2 heterozygous genotype showed a protective effect (AS 5.97% vs. normal 11.66%; p = 0.002; pFDR = 0.0127, OR, 0.48 95% CI: 0.33–0.70); in contrast, KIR 2DS4/1D combined with the HLA-C1C1 homozygous genotype (AS 45.33% vs. normal 35.92%; p = 0.002; pFDR = 0.0127, OR, 1.48 95% CI: 1.21–1.81) represented a risk factor for AS development. Our data suggested that interactions between KIRs and their cognate HLA-C ligands may contribute to the pathogenesis of AS.

IgG Fcγ receptors (FcγRs) mediate a variety of immune functions that are critical in immune responses. In humans, 5 classic low-affinity FcγRs (FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, and FcγRIIIB) are coded by 5 genes (FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B, respectively) in the FCGR cluster on chromosome 1. Activating FcγRs (FcγRIIA, FcγRIIC, FcγRIIIA, and FcγRIIIB) mediate immune cell activation promoting inflammation, while the classic inhibitory FcγRIIB dampens immune responses and restricts inflammation (1,2). Activating FcγRs mediate functions including immune complex clearance, phagocytosis, antigen presentation, antibody-dependent cellular cytotoxicity, and cytokine production (3). In contrast, the inhibitory FcγRIIB abrogates immune cell activation. FcγRIIB also plays a role in the maintenance of peripheral B cell tolerance and the prevention of autoimmunity (2). The variations in FcγR expression significantly affect IgG immune complex–mediated signal thresholds (3,4). Notably, proinflammatory and antiinflammatory cytokines could modulate the expression levels of activating and inhibitory FcγRs (5) that affect the threshold immune cell response to IgG immune complexes (6). FcγR-knockout mouse models indicate that both activating and inhibitory FcγRs influence the development of autoimmune diseases (7–9). The contributions of FcγR genes to autoimmune diseases have attracted substantial attention, and functional FcγR polymorphisms have been reported to play important roles in the pathogenesis of autoimmune diseases (4,10,11). Gene copy number variation (CNV) is a rich source of genetic heterogeneity (12,13). The FCGR cluster on chromosome 1q23 shows a complex pattern of CNVs. Among 5 FcγR genes in the cluster, 3 genes (FCGR3A, FCGR2C, and FCGR3B) have CNVs, while FCGR2A and FCGR2B do not have CNVs (14,15). CNVs play important roles in human disease pathogenesis (16). FCGR3B copy number deficiency is associated with autoimmune disease, including systemic lupus erythematosus (SLE) (17–19), Sjogren's syndrome (20), and systemic sclerosis (21). Although FCGR3B CNVs were reported to associate with rheumatoid arthritis (RA) (22–24), no association between RA and FCGR3B CNVs was observed in other studies (25,26). Moreover, no association between FCGR3A CNVs and RA was observed (24,27). In the current study, we investigated whether FCGR3A and FCGR3B CNVs are associated with susceptibility to SLE and RA in Taiwanese individuals. The results provide new insights into the role of FcγRIII family members in the pathogenesis of SLE and RA in an Asian population.

Huang-Shen Lin,1,2 Chun-Wen Cheng,3 Ming-Shyan Lin,4 Yen-Li Chou,5 Pey-Jium Chang,2 Jing-Chi Lin,6 Jung-Jr Ye3 1Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Chia-Yi, 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 3Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, 4Division of Cardiology, Chang Gung Memorial Hospital, Yunlin, 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Chia-Yi, 6Division of Allergy and Immunology and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chia-Yi, Taiwan Objectives: To investigate the clinical characteristics, adverse drug reactions, and outcomes of the oldest old patients (aged ≥80years) with tuberculosis (TB) treated with rifampicin, isoniazid, and pyrazinamide (RIP)-containing regimens. Design: A retrospective chart review study. Setting: A 1,200-bed tertiary teaching hospital in southwest Taiwan. Participants: We conducted a retrospective observational study between January 1, 2005 and December 31, 2011. Seven hundred adult patients (aged ≥18years) with TB treated with RIP-containing anti-TB regimens were reviewed, including 161 oldest old patients. Outcome measures: Clinical outcomes included clinical responsiveness and microbiological eradication. Adverse outcomes included drug-induced hepatitis, and other symptoms included gastrointestinal upset (eg, abdominal pain, vomiting, diarrhea, or dyspepsia), skin rash, joint pain, and hyperuricemia. Results: Compared with the non-oldest old adult patients, the oldest old patients more frequently had hepatitis (P=0.014), gastrointestinal upset (P=0.029), and unfavorable outcomes (P

This study investigated the interrelationship between Lycium barbarum (goji) and gene expression in mouse spleen. Oligomicroarray technology was employed to explore the comprehensive response of gene expression and to screen candidate marker genes in the spleens of mice fed a goji suspension. Goji was micronized by media milling and then used to evaluate the effect of size reduction. The average diameter of nano/submicrometer goji was about 100 nm, which exhibited no cytotoxicity to cell lines IEC-6 (rat normal small intestinal cell line) and Caco-2 (human colon adenocarcinoma cell line). It was found that three genes, TNF, Nfkb1, and Bcl-2, were up-regulated and two genes, APAF-1 and caspase-3, were down-regulated by goji. This phenomenon could be helpful for cytoprotection when cells undergo stress or damage that induces the apoptotic pathway. Size reduction into nano/submicrometer scale enhanced bioactivity.

The aim of this study was to investigate treatment response and hepatic safety of anti-tumor necrosis factor-α therapy among patients with concomitant rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection. We reviewed the charts of 101 consecutive RA patients who were eligible for anti-TNF-α therapy in the Chiayi Branch of Chang Gung Memorial Hospital. Group A patients were sero-positive for anti-HCV antibodies and had HCV RNA but were negative for hepatitis B surface antigen (HBsAg). Group B (the control group) patients were sero-negative for both anti-HCV antibodies and HBsAg. Response to anti-TNF-α treatment was assessed by calculating disease activity score at 28 joints (DAS28) at baseline and 5, 8, and 11 months after the start of TNF-α antagonist therapy. Percentage change in DAS28 from baseline to month 5 was 21.36 ± 8.01 % in group A and 26.98 ± 10.43 % in group B (p = 0.011). However, there was no obvious difference in treatment response between groups at other time points. Anti-TNF-α therapy was discontinued within 1 year of starting treatment in two subjects in group A and 4 in group B. Response to anti-TNF-α was better in group B than in group A at 5 months, but there was no substantial difference in response at the 1-year evaluation. Although the study sample was small, our results suggest that the safety of anti-TNF-α therapy is similar in RA patients with and without concomitant HCV infection.

The negative association between gout and rheumatoid arthritis is widely accepted, and gout is also speculated to be rare in systemic lupus erythematosus (SLE), as only a few sporadic cases have been reported. From 1985 to 2001 we encountered 15 lupus patients at Chang-Gung Memorial Hospital, including two with lupus-scleroderma and one with lupus-scleroderma-polymyositis overlap syndrome coexisting with gout. This study retrospectively analyses the clinical and laboratory characteristics of these patients. A lower female predominance is found, and most patients developed gout after the onset of SLE, although gout preceded SLE in two cases. Measurement of serum uric acid and 24-h urine uric acid found all of the patients to be hyperuricaemic and underexcretors of uric acid. Furthermore, most of the patients (14/15) were receiving diuretics. Also, many had hypertension and serious cardiovascular diseases. Renal impairment during gouty attacks seemed to be a predisposing factor for developing end-stage renal disease. Gouty arthritis usually occurred during relative SLE inactivity, podagra was frequent, and tophi were found in a few patients. Compared with the unselected population of SLE patients, the cases studied here had a higher incidence of chronic arthritis, malar rash, haematologic disorder, photosensitivity, serositis and neurologic disorder. Renal disease in the patients sampled was frequently membranous nephropathy.

OBJECTIVE The aim of the present study was to investigate the effect of gout on left ventricular (LV) diastolic function and left atrial volume (LAV). METHODS A total of 173 patients were divided into four groups: control (n = 35), asymptomatic hyperuricaemia (n = 30), gouty arthritis without tophi (n = 58) and gouty tophi (n = 50). Patients underwent a comprehensive Doppler echocardiography examination to evaluate LV volume, systolic and diastolic function and LAV and function. RESULTS Serum uric acid levels were not significantly different in the asymptomatic hyperuricaemia, gouty arthritis without tophi and gouty tophi groups. However, the ratio of the transmitral and myocardial peak early diastolic velocities (E/e') and LAV index (LAVi) progressively increased from the control group to the gouty tophi group. The tophi group had significantly higher E/e' [10.5 (s.d. 3.2) vs 8.6 (s.d. 2.1), P = 0.008] and larger maximal, pre-contraction and minimal LAVi [29.6 ml/m(2) (s.d. 9.9) vs 20.1 ml/m(2) (s.d. 4.8); 19.1 ml/m(2) (s.d. 8.5) vs 11.5 ml/m(2) (s.d. 3.4); 9.6 ml/m(2) (s.d. 4.2) vs 6.1 ml/m(2) (s.d. 2.2); all P < 0.001] than the control group. By binary logistic analysis, maximal LAVi was an independent predictor for the development of tophi in gout patients, with an odds ratio of 1.068 (95% CI 1.02, 1.118; P = 0.005). CONCLUSION The severity of gout had a significant effect on LV diastolic dysfunction and LA enlargement in gout patients. Additionally, a high maximal LAVi predicted the development of tophi and may be a predictor of adverse cardiovascular events related to LA and LV remodelling in this clinical setting.

Toll-like receptors (TLRs), as innate immunity sensors, play critical roles in immune responses. Six SNPs of TLR3, TLR7, and TLR8 were genotyped to determine their associations with systemic lupus erythematosus (SLE) and clinical manifestations of SLE. TLR7 SNP rs3853839 was independently associated with SLE susceptibility in females (G vs. C: p = 0.0051). TLR7 rs3853839-G (G vs. C: p = 0.0100) and TLR8 rs3764880-G (recessive model: p = 0.0173; additive model: p = 0.0161) were associated with pericardial effusion in females relative to healthy females. Anti-SSA positive cases were more likely to have the dominant TLR7 rs179010-T allele than normal controls (p = 0.0435). TLR3 rs3775296-T was associated with photosensitivity (p = 0.0020) and anemia (p = 0.0082). The "G-G" haplotype of TLR7 rs3853839 and TLR8 rs3764880 increased risk of SLE in females (age adjusted p = 0.0032). These findings suggest that TLR variations that modify gene expression affect risk for SLE susceptibility, clinical phenotype development, and production of autoantibodies.

Introduction Ankylosing spondylitis (AS) is a familial, heritable disease specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to be associated with AS in several ethnic populations. The aim of this study was to investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated with AS susceptibility and disease severity in Taiwanese. Methods Four ERAP1 SNPs (rs27037, rs27980, rs27044 and rs30187) were genotyped in 797 Taiwanese AS patients and 1,150 healthy controls. Distributions of genotype and alleles were compared between AS patients and healthy controls, and among AS patients stratified by clinical parameters. Results The SNP rs27037T allele appeared to be a risk factor for AS susceptibility (P = 5.5 × 10-5, OR 1.30, 95% CI: 1.15 to 1.48; GT+TT vs. GG P = 9.3 × 10-5, OR 1.49, 95% CI: 1.22 to 1.82). In addition, the coding SNP (cSNP) rs27044G allele (P = 1.5 × 10-4, OR 1.28, 95% CI: 1.13 to 1.46; CG+GG vs. CC, P = 1.7 × 10-3, OR 1.44, 95% CI: 1.15 to 1.81) and the cSNP rs30187T allele (P = 1.7 × 10-3, OR 1.23, 95% CI: 1.08 to 1.40; CT+TT vs. CC P = 6.1 × 10-3, OR 1.38, 95% CI: 1.10 to 1.74) were predisposing factors for AS. Notably, the rs27044G allele carriers (CG+GG vs. CC, P = 0.015, OR 1.59, 95% CI: 1.33 to 2.30) and rs30187T allele carriers (CT+TT vs. CC, P = 0.011, OR 1.63, 95% CI: 1.12 to 2.38) were susceptible to syndesmophyte formation in AS patients. Furthermore, two cSNPs (rs27044 and rs30187) strongly associated with HLA-B27 positivity in AS patients. Finally, the ERAP1 SNP haplotype TCG (rs27037T/rs27980C/rs27044G) is a major risk factor for AS (adjusted P

The purpose of our study was to evaluate the left ventricular (LV) and left atrial (LA) function in patients with gout. A total of 173 patients underwent a comprehensive Doppler-echocardiography examination. Participants were divided into four groups-Stage 0: control (n = 35), Stage I: asymptomatic hyperuricemia (n = 30), Stage II: gouty arthritis without tophi (n = 58), and Stage III: tophaceous gout (n = 50). Serum uric acid levels were not significantly different between stage I, II and III. Stage III patients demonstrated a higher ratio of the transmitral and myocardial peak early diastolic velocities (E/Em) (10.50 ± 3.18 vs. 8.58 ± 2.07; P = 0.008), and larger maximal LA volume index (LAVi) (29.60 ± 9.89 vs. 20.07 ± 4.76 ml/m(2); P

The B-cell depletion agent rituximab (RTX) is used in lymphoma and rheumatoid arthritis (RA), and there have been several case reports of an RTX-induced reactivation of hepatitis C virus in patients with lymphoma. However, there have been no papers detailing hepatitis C virus reactivation after RTX therapy in a patient with RA. Here we report a case of RTX-induced hepatitis C virus reactivation in a patient with RA. Physicians should be aware that a close follow-up of liver function and viral load is mandatory after RTX therapy in patients with RA and concomitant hepatitis C.

Introduction Gout is a common metabolic disorder characterized by hyperuricemia and chronic inflammation. Previous studies show that hyperuricemia accelerates the occurrence and worsening of cardiovascular disease due to LV remodeling. However, it is still unclear whether hyperuricemia is the sole contributor to organic heart remodeling in patients with gout. In addition, there is a paucity of data regarding the association between LV diastolic function and gout. The objective of this study was to investigate the effects of gout on LV diastolic function. Methods A total of 173 patients were divided into tertiles based on the following serum uric acid (UA) levels: 1) serum UA ≤ 6.5 mg/dL (n = 54), 2) serum UA >6.5 to ≤8.5 mg/dL (n = 59), and 3) serum UA > 8.5 mg/dL (n = 60).Patients underwent a comprehensive Doppler-echocardiography examination to evaluate LV volume, systolic and diastolic function, and left atrial (LA) volume. Results LV diastolic parameters, including diastolic peak early transmitral flow velocity (E), late transmitral flow velocity (A), E/A, peak early diastolic mitral annular velocity (Em), late diastolic annular velocity (Am), Em/Am, E/Em, maximal LA volume index (LAVi) and prevalence of moderate to severe LV diastolic dysfunction were not significantly different between the three groups. Among the population being studied, 108 individuals received a gout diagnosis. Gout patients had greater LV end-systolic dimensions (27.08 ± 4.38 mm, p = 0.006), higher LV mass index (107.18 ± 29.51 g/m2, p