A two sample mendelian randomization analysis investigates causal effects between gut microbiome and immune related Vasculitis.

Observational data suggest a link between gut microbiota and immune-related vasculitis, but causality remains unclear. A bidirectional mendelian randomization study was conducted using public genome-wide data. The inverse-variance-weighted (IVW) method identified associations and addressed heterogeneity.Families Clostridiaceae 1 and Actinomycetaceae correlated positively with granulomatosis with polyangiitis risk, while classes Lentisphaeria and Melainabacteria, and families Lachnospiraceae and Streptococcaceae showed negative associations. Behçet's disease was positively associated with the risk of family Streptococcaceae abundance. And other several gut microbiota constituents were identified as potential risk factors for immune-related vasculitis. Furthermore, combining positive association results from the IVW analysis revealed numerous shared gut microbiota constituents associated with immune-related vasculitis. MR analysis demonstrated a causal association between the gut microbiota and immune-related vasculitis, offering valuable insights for subsequent mechanistic and clinical investigations into microbiota-mediated immune-related vasculitis.

Serum concentrations of small dense low-density lipoprotein cholesterol and lipoprotein(a) are related to coronary arteriostenosis in Takayasu arteritis.

BACKGROUND: Serum small dense low-density lipoprotein cholesterol (sdLDL-C) and lipoprotein(a) [Lp(a)] levels are related to coronary disease, but their specific associations with coronary arteriostenosis in Takayasu arteritis (TA) have not been ascertained. This study explored the correlations between serum sdLDL-C and Lp(a) levels and coronary arteriostenosis in TA patients as well as the degree of artery stenosis. METHODS: This retrospective study included 190 TA patients and 154 healthy subjects. TA patients were divided into three categories based on the degree of coronary stenosis: Group I, stenosis >50%; Group II, stenosis 1%-50%; and Group III, stenosis 0%. Independent risk factors for coronary arteriostenosis in TA were identified by logistic regression, followed by receiver operating characteristic curve analysis to determine the specificity and sensitivity of risk factors and Youden's Index score calculation to determine the cutoff points. RESULTS: Takayasu arteritis patients had significantly higher serum levels of sdLDL-C and Lp(a) than healthy controls (p < 0.0001). The total cholesterol, triglyceride, LDL-C, sdLDL-C, and Lp(a) levels and the sdLDL-C/LDL-C ratio in Group I were significantly higher than those in Groups II and III (p < 0.05). An elevated serum sdLDL-C level elevated the risk of coronary arteriostenosis by 5-fold (cutoff value, 0.605 mmol/l). An increased serum Lp(a) level increased the risk of coronary arteriostenosis by 3.9-fold (cutoff value, 0.045 g/l). An elevated sdLDL-C/LDL-C ratio increased the risk of coronary arteriostenosis by 2.1-fold (cutoff value, 0.258). CONCLUSIONS: Serum sdLDL-C and Lp(a) levels and sdLDL-C/LDL-C ratio may be used as diagnostic factors for coronary arteriostenosis in TA patients.

Serum C1q concentration is associated with disease activity in Chinese Takayasu arteritis patients: A case-control study.

BACKGROUND: C1q is a crucial component of the classical complement pathway. This study is the first to assess the association between disease activity and serum levels of C1q in Chinese Takayasu arteritis (TA) patients. METHODS: Serum C1q levels in 198 TA patients and 154 healthy controls were assessed, and the relationship between serum C1q levels and indices of TA disease activity was analyzed. Moreover, we examined the correlation between serum C1q levels and two traditional inflammatory biomarkers; erythrocyte sedimentation rate (ESR) and hypersensitive CRP (hs-CRP). RESULTS: Serum C1q levels were increased in TA patients compared with healthy controls (P = .008). TA patients with active disease had higher levels of serum C1q than patients who had inactive disease (P < .0001). In addition, treatment-naïve patients had higher serum C1q levels than those who had been treated with corticosteroids or at least one immunosuppressant (P = .001). Furthermore, a positive correlation between serum C1q levels and traditional inflammatory biomarkers in TA patients was found. The role of C1q in assessing disease activity was studied, and the area under the receiver operating characteristic curve (AUC) of C1q for predicting active disease was 0.752, and a serum cutoff value of 167.15 mg/L C1q maximized the ability of disease activity assessment, with a sensitivity/specificity of 77.80%/64.90%. When the three indicators (C1q, ESR, and hs-CRP) were combined, the AUC increased to 0.845, and the sensitivity to 84.40%. CONCLUSIONS: The serum C1q is associated with the disease activity of TA and the combination of three indicators (C1q, ESR, and hs-CRP) increases the sensitivity of disease activity assessment.

The relationships of serum homocysteine levels and traditional lipid indicators with disease activity and coronary artery involvement in Takayasu arteritis.

Serum homocysteine (HCY) levels have been associated with the occurrence of coronary stenosis and disease activity in large-vessel vasculitis. However, whether increases in serum HCY levels and traditional lipid indicators are associated with coronary artery involvement and disease activity in Chinese Han Takayasu arteritis (TA) patients is unknown. This study aims to investigate the clinical and laboratory features of TA by assessing their association with disease activity in TA patients, and to explore the risk factors associated with coronary artery involvement in these patients. Serum HCY levels and traditional lipid indicators were tested in one hundred ninety TA patients and one hundred fifty-four healthy controls. We analyzed the relationships of serum HCY levels and traditional lipid indicators with disease activity and analyzed the risk factors for coronary artery involvement. Twenty-one TA patients were found to have coronary artery stenosis (≥ 50%). TA patients had significantly higher levels of HCY than did healthy controls (p < 0.0001). Serum levels of HCY and low-density lipoprotein cholesterol (LDL-C); the ratios of LDL-C to high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) to HDL-C, and triglycerides (TG) to HDL-C; and the values of atherogenic index of plasma (AIP) were significantly higher in patients with active TA than in patients with inactive TA and in TA patients with coronary artery involvement than in TA patients without coronary artery involvement. By contrast, the serum levels of HDL-C were significantly lower in patients with active TA than in patients with inactive TA and in TA patients with coronary artery involvement than in TA patients without coronary artery involvement (p < 0.05). In addition, the serum levels of TC and TG were significantly higher in TA patients with coronary artery involvement than those in TA patients without coronary artery involvement. Elevated serum HCY levels increased the risk of coronary artery involvement by 1.3-fold (p = 0.011, odds ratio [OR] = 1.275, 95% confidence interval [CI]: 1.056-1.539), and the cutoff value for serum HCY was 9.55 µmol/L. Elevated serum TG levels increased the risk of coronary artery involvement by 3.5-fold (p < 0.0001, OR = 3.534, 95% CI: 1.907-6.547), and the cutoff value for serum TG was 1.215 mmol/L. The risk of coronary artery involvement was 2.5-fold higher when an elevated TG/HDL-C ratio was present (p < 0.0001, OR = 2.513, 95% CI: 1.567-4.032). This study showed that serum HCY and TG levels and the TG/HDL-C ratio are independent risk factors for coronary artery involvement in TA patients.

Correlation Between Extended Leukocyte Differential Count and Coronary Artery Disease.

BACKGROUND: Leukocyte count is closely associated with the risk of coronary artery disease (CAD). Levels of leukocyte subpopulations in patients with CAD, however, remain largely unknown. METHODS: In this study, we compared the distributions and counts of 16 leukocyte subpopulations between 40 patients with CAD and 40 healthy controls using the CytoDiff flow cytometric system. RESULTS: Our results demonstrated significant increases in the frequencies and counts of all monocytes, immature granulocytes, and B-lymphocytes in patients with CAD, suggesting that the levels of these leukocyte subpopulations may serve as potential biomarkers for diagnosis of CAD. By contrast, the levels of cytotoxic T/natural killer lymphocytes were markedly decreased in patients with CAD. In addition, the levels of T/natural killer lymphocytes, noncytotoxic T-lymphocytes, mature neutrophils, total neutrophils, eosinophils, basophils, and T-cell blasts in CAD patients with elevated levels of cardiac troponin I (cTnI), an independent indicator for poor prognosis in CAD, were significantly different from those in CAD patients with normal levels of cTnI. These data may help in the screening for biomarkers to discriminate between stable and unstable patients with CAD. CONCLUSIONS: Collectively, our results provide a detailed distribution profile of leukocyte subpopulations in patients with CAD and suggest their possible clinical application in predicting the risk and severity of CAD.

Elevated soluble ST2 concentration may involve in the progression of atrial fibrillation.

BACKGROUND: The aim of this study is to investigate the value of soluble suppression of tumorigenicity 2 (sST2) in Atrial fibrillation (AF) patients' risk prediction. METHODS: Healthy people (n = 60) and AF patients (n = 194) were consecutively enrolled into this project. RESULTS: In the health group, the mean age was 54 y (55% males). Serum median concentration of sST2 in healthy individuals was 17.04 ng/ml. In the AF patients group, the mean age was 61 years, and 64% were males. Median sST2 value was 21.69 ng/ml. According to subgroup analysis, median sST2 value of paroxysmal and persistent AF patients was 19.82 ng/ml and 24.15 ng/ml, respectively. Emergency AF patients showed much higher median sST2 concentration than AF outpatients (41.59 ng/ml vs. 20.53 ng/ml, p < 0.01). By multiple linear regression analysis adjusted for age and sex, heart failure (HF) and BNP strongly associated with sST2 concentration. After healthy people and AF patients with HF excluded, whether emergency visit or not become a patent predictor of sST2 concentration (n = 172). CONCLUSION: sST2 is probably an objective biomarker that can predict AF patients' risk of emergency admission or HF. Elevated sST2 concentration may involve in the progression of AF.

Relationship of HLA-B*51 and HLA-B*52 alleles and TNF-α-308A/G polymorphism with susceptibility to Takayasu arteritis: a meta-analysis.

We performed a meta-analysis to determine whether combined evidence shows an association between HLA-B*51 and HLA-B*52 alleles and TNF-α-308A/G polymorphism and the susceptibility to Takayasu arteritis (TA). Relevant articles dated November 2015 were acquired from the PubMed, Embase and Cochrane databases. The number of genotypes and/or alleles for HLA-B*51 and HLA-B*52 alleles and TNF-α-308 A/G polymorphism in cases and control subjects was extracted, and statistical analysis was conducted using STATA 11.2 software. We included 20 studies with 1864 TA patients and 6973 controls. The HLA-B*52 allele was found to be associated with TA (pooled OR 3.91, 95 % CI 3.22-4.74, P < 0.0001). The meta-analysis of TNF-α-308 A/G polymorphism for the A allele vs. G allele (P = 0.006) and AA + AG vs. GG (P = 0.023) revealed a significant association with TA. However, we did not find that the HLA-B*51 allele was associated with TA. This meta-analysis demonstrated that the HLA-B*52 allele and TNF-α-308 A/G polymorphism may contribute to TA susceptibility.

A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23.

Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sjögren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 × 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjögren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.

A single-nucleotide polymorphism of the STAT4 gene is associated with systemic lupus erythematosus (SLE) in female Chinese population.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Genetic association of signal transducer and activator of transcription 4 (STAT4) with SLE susceptibility has been convincingly established in multiple populations including Asians, whereas studies of genetic relations between STAT4 polymorphisms and subphenotypes of SLE were rarely conducted. In this study, we selected Chinese female population and investigated genetic association between a polymorphism of STAT4 gene (rs7582694) and SLE. Furthermore, genetic association tests based on different subsets classified by 11 clinical manifestations were also performed. A total of 675 SLE female patients and 678 healthy controls were enrolled into this study, and SNP genotyping was performed using Sequenom's MassArray system (Sequenom iPLEX assay). Our study showed strong evidence for genetic predisposition of rs7582694 to SLE (X ( 2 ) = 23.7, OR = 0.68, 95% CI: 0.58-0.79, P = 1.13 × 10(-6)), while no association was observed between rs7582694 and any clinical presentations. The results of our study demonstrated that STAT4 rs7582694 SNP was significantly associated with SLE, and these results were in accordance with previous studies.

Association of genetic variations in the STAT4 and IRF7/KIAA1542 regions with systemic lupus erythematosus in a Northern Han Chinese population.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Genome-wide association studies have identified SLE susceptibility variations at the IRF7/KIAA1542 locus and with STAT4 gene in European populations. We decided to investigate the association of single-nucleotide polymorphisms (SNPs) in the IRF7/KIAA1542 region (rs4963128, rs2246614, and rs702966) and in STAT4 (rs7574865 and rs7582694) with SLE disease in a Northern Han Chinese population of 748 patients and 750 healthy controls. Our study indicated a strong association between rs7574865 (odds ratio = 0.68; 95% confidence interval 0.59-0.79; p = 1.57 × 10(-6)) and SLE and between rs7574865 and the production of anti-Sm antibodies. Additionally, rs4963128 and rs2246614 were correlated with a variety of clinical subphenotypes, such as lupus nephritis, arthritis, and the production of anti-SSA/B autoantibodies, despite a lack of significant association between these two SNPs and SLE disease susceptibility in general.

Expression of matrix metalloproteinase-1 mRNA in peripheral blood mononuclear cells of systemic lupus erythematosus patients and its relationship with atherosclerosis.

BACKGROUND: Matrix metalloproteinase-1 (MMP-1) plays an important role in atherosclerosis. This study was to examine expression of MMP-1 mRNA in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), and to explore its relationship with atherosclerosis in SLE. METHODS: Fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of MMP-1 mRNA in PBMCs in 80 SLE patients, including 39 prone to atherosclerosis (Group A) and 41 unprone to atherosclerosis (Group B). Meanwhile, 30 patients who were free of cardiovascular diseases and 30 healthy individuals were selected as disease and normal control group (Groups C and D). The changes of MMP-1 gene expression were analyzed by differences of cycle threshold (DeltaCt), with the following formula: DeltaCt = Ct(target) gene - Ct(reference) gene. RESULTS: The expression level of MMP-1 mRNA in Group A was significantly higher than that of group B (DeltaCt = 8.64 +/- 2.43 vs DeltaCt = 12.09 +/- 2.26, t = 6.588, P < 0.01). The expression level of MMP-1 mRNA of SLE patients was significantly higher than that of Group C (DeltaCt = 10.41 +/- 2.90 vs DeltaCt = 12.29 +/- 2.51, t = 3.135, P < 0.01) and Group D (DeltaCt = 10.41 +/- 2.90 vs DeltaCt = 12.48 +/- 1.69, t = 3.675, P < 0.01). CONCLUSIONS: In comparison to disease and control group, expression of MMP-1 mRNA in PBMCs of SLE patients was significantly elevated, and significant difference of MMP-1 mRNA expression was also found between SLE patients prone and unprone to atherosclerosis, indicating that expression of MMP-1 mRNA may be correlated with the pathogenesis and activity of atherosclerosis in SLE.