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Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of anti-phospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role ofanti-phosphatidylserine (PS) autoantibodies in the development of LN. In cohort study and mouse models, elevated serum PS-specific IgG levels were detected in SLE patients, especially in those with nephritis, and lupus mice. The deposition of PS-specific IgG was detected in kidney biopsied of lupus nephritis patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type for secreting PS-specific IgG in both lupus mice and patients. Adoptive transfer of PS-specific B1a cells accelerated PS-specific autoimmune response and renal damage in recipient lupus mice whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components while blockade of TLR signal cascades by DNase I digestion, inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the novel anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of TLR/Syk signaling cascade inhibits PS-specific B1 cell expansion may provide new insight in understanding lupus pathogenesis and may help develop novel therapeutic targets for the treatment of LN in SLE.

Background: To assess the diagnosis significance of the serum Krebs von den Lungen-6 (KL-6) for the interstitial lung disease (ILD) related to primary Sjögren syndrome(pSS-ILD) Methods: An overall 79 pSS-ILD sufferers and 71 pSS sufferers from our hospital between Jan 2015 and May 2021 were enrolled. The measuring of serum KL-6, lung function testing, and high-resolution computed tomography (HRCT) completed simultaneously were studied. Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA).Correlative analyses and receiver-operator characteristic (ROC) analyses were completed to identify the value of the aforesaid measuring results.Results: The remarkably higher contents of KL-6 were identified in pSS-ILD patients in contrast to pSS patients [795.1±725.3U/ml vs 198.6±77.5U/ml] (P＜0.001). The optimum threshold of serum KL-6 for the diagnoses of ILD was 276.5 U/ml, and the sensitivity and specificity were 87.3% and 88.7%, respectively. The area under the curve (AUC) was 0.919 and the logistic regression analysis revealed that elevated KL-6 and decreased carbon monoxide diffusion capacity were independently correlated with the occurrence of pSS-ILD, and the increase of KL-6 levels was an independent risky factor for the occurrence of ILD (OR=1.019, 95%CI: 1.010~1.029). Conclusion: The serum KL-6 is a vital marker for the diagnoses of pSS-ILD, and when the KL-6 content is elevated, there is an underlying risk of ILD.

Interstitial lung disease (ILD) is a major complication of Primary Sjögren's syndrome (pSS) patients.It is one of the main factors leading to death. The aim of this study is to evaluate the value of serum Raman spectroscopy combined with machine learning algorithms in the discriminatory diagnosis of patients with Primary Sjögren's syndrome associated with interstitial lung disease (pSS-ILD).Raman spectroscopy was performed on the serum of 30 patients with pSS, 28 patients with pSS-ILD and 30 healthy controls (HC). First, the data were pre-processed using baseline correction, smoothing, outlier removal and normalization operations. Then principal component analysis (PCA) is used to reduce the dimension of data. Finally, support vector machine(SVM), k nearest neighbor (KNN) and random forest (RF) models are established for classification.In this study, SVM, KNN and RF were used as classification models, where SVM chooses polynomial kernel function (poly). The average accuracy, sensitivity, and precision of the three models were obtained after dimensionality reduction. The Accuracy of SVM (poly) was 5.71% higher than KNN and 6.67% higher than RF; Sensitivity was 5.79% higher than KNN and 8.56% higher than RF; Precision was 6.19% higher than KNN and 7.45% higher than RF. It can be seen that the SVM (poly) had better discriminative effect. In summary, SVM (poly) had a fine classification effect, and the average accuracy, sensitivity and precision of this model reached 89.52%, 91.27% and 89.52%, respectively, with an AUC value of 0.921.This study demonstrates that serum RS combined with machine learning algorithms is a valuable tool for diagnosing patients with pSS-ILD. It has promising applications.

Evidence of active tuberculosis (ATB) in patients with rheumatic diseases are research priorities but limited data from China have been reported. Research targeting patients not taking anti-TNF biologics are especially insufficient. We aimed to investigate the prevalence and risk factors of ATB in this at-risk population. We conducted a tertiary hospital-based, multi-center, cross-sectional study by using stratified multi-stage cluster sampling strategy to screen ATB in patients with rheumatic diseases. We estimated the prevalence of ATB in patients with rheumatic diseases and identified risk factors among those who were not taking anti-TNF biologic. A total of 13,550 patients with rheumatic diseases were enrolled, and the result showed the standardized prevalence of ATB according to the composition ratio of various types of rheumatic disease was 882/100000 (95% confidence interval (CI): 706-1057). Multivariable logistic regression analysis in patients not taking anti-TNF biologics showed that the independent risk factors of ATB were having systemic lupus erythematosus (SLE) (OR=2.722, 95% CI: 1.437-5.159, p=0.002), having Behcet's disease (BD) (OR= 5.261, 95% CI: 2.071-13.365, p

Objectives This study aims to determine a role of interleukin‐17A (IL‐17) in salivary gland (SG) dysfunction and therapeutic effects of targeting IL‐17 in SG for treating autoimmune sialadenitis in primary Sjögren’s syndrome (pSS). Methods Salivary IL‐17 levels and IL‐17‐secreting cells in labial glands of pSS patients were examined. Kinetic changes of IL‐17‐producing cells in SG from mice with experimental Sjögren’s syndrome (ESS) were analysed. To determine a role of IL‐17 in salivary secretion, IL‐17‐deficient mice and constructed chimeric mice with IL‐17 receptor C (IL‐17RC) deficiency in non‐hematopoietic and hematopoietic cells were examined for saliva flow rates during ESS development. Both human and murine primary SG epithelial cells were treated with IL‐17 for measuring cholinergic activation‐induced calcium movement. Moreover, SG functions were assessed in ESS mice with salivary retrograde cannulation of IL‐17 neutralisation antibodies. Results Increased salivary IL‐17 levels were negatively correlated with saliva flow rates in pSS patients. Both IL‐17‐deficient mice and chimeric mice with non‐hematopoietic cell‐restricted IL‐17RC deficiency exhibited no obvious salivary reduction while chimeric mice with hematopoietic cell‐restricted IL‐17RC deficiency showed significantly decreased saliva secretion during ESS development. In SG epithelial cells, IL‐17 inhibited acetylcholine‐induced calcium movement and downregulated the expression of transient receptor potential canonical 1 via promoting Nfkbiz mRNA stabilisation. Moreover, local IL‐17 neutralisation in SG markedly attenuated hyposalivation and ameliorated tissue inflammation in ESS mice. Conclusion These findings identify a novel function of IL‐17 in driving salivary dysfunction during pSS development and may provide a new therapeutic strategy for targeting SG dysfunction in pSS patients., In this study, we found that increased salivary IL‐17 levels were negatively correlated with saliva flow rates in patients with primary Sjögren’s syndrome (pSS). We further identified a novel function of IL‐17 in driving salivary dysfunction by impairing transient receptor potential canonical 1‐mediated calcium movement during pSS pathogenesis. This pre‐clinical study demonstrated that neutralization of IL‐17 in salivary glands attenuated hyposalivation and ameliorated tissue inflammation in mice with experimental SS, suggesting a therapeutic potential of local targeting IL‐17 for treating xerostomia and autoimmune sialadenitis in pSS patients.

ObjectivesLack of effective biomarkers in anti-citrullinated protein antibody (ACPA)-negative rheumatoid arthritis (RA) impedes early diagnosis and treatment. This study aimed to identify novel autoantibodies in RA and verify their diagnostic values in ACPA-negative RA based on protein microarray technology.MethodsA total of 1011 sera from 559 RA (276 ACPA-positive and 283 ACPA-negative), 239 disease controls (DCs) and 213 healthy controls (HCs) were collected and sampled on two sequential microarrays and ELISA and western blot (WB) detection, for novel autoantibodies discovery, validation and verification, respectively. The high-density protein microarray printed with a broad spectrum of recombinant human proteins was first employed to screen candidate autoantibodies, then focused microarrays composed of candidate autoantigens were used for validation, followed by ELISA and WB to verify the presence of the most promising candidates in ACPA-negative RA.ResultsNine novel autoantibodies were identified by two sequential microarrays with positivity 17.93%–27.59% and specificities >90% in ACPA-negative RA. Among these, anti-PTX3 and anti-DUSP11 autoantibodies presented with the highest sensitivity and were consistently verified by ELISA and WB. Pooling samples of all cohorts, the positivities of anti-PTX3 and anti-DUSP11 in ACPA-negative RA were 27.56% and 31.80%, respectively, similar to those in ACPA-positive RA, and significantly higher than in HCs (4.69% and 2.35%) and DCs (10.04% and 8.49%) (pConclusionAnti-PTX3 and anti-DUSP11 autoantibodies are newly identified biomarkers for diagnosis of ACPA-negative RA.

to investigate the prevalence of hyperuricemia (HUA) in Kazak population in Fuhai county, Xinjiang Aletai area.A randomized cross-sectional cluster sampling was performed in Kazaks in Fuhai. A total of 2 006 inhabitants were investigated by household survey. The questionnaires were completed for general performance, past illness history and family history. Height, weight, body mass index (BMI) and blood pressure were measured and recorded. Fasting blood samples were collected for serum uric acid and other biochemical tests.(1) Finally a total of 1 921 Kazaks were enrolled.The serum uric acid level in Kazaks in Fuhai was (234.11 ± 82.56) μmol/L, which was higher in males (287.48 ± 80.27) μmol/L than that in females (201.03 ± 64.74) μmol/L (P0.001). In HUA group, serum uric acid level also had significant difference between men and women [(498.93 ± 130.24) μmol/L vs (471.20 ± 167.71) μmol/L; P = 0.044]. (2) the prevalence of HUA in Kazak general population was 2.97% (57/1 921). After standardization according to the natural population survey in 2000, the standardized rate in general group was 3.34%, in which the prevalence in males (4.76%, standardized rate was 4.64%) was higher than that in females (1.85%, standardized rate was 1.88%) (P0.001). There was no gout found in 1 921 Kazaks in Fuhan when the study was taken. (3) Cohorts of different dietary habit ( who preferred vegetable or meat or both of them) who had drunk alcohol had higher prevalence of HUA than those with vegetarian diet without alcohol group (7.69%, 5.66% and 5.62% vs 0.78%; all P0.05). The cohort who preferred animal food with alcohol had higher prevalence of HUA than those who preferred both vegetable and meat without alcohol (5.66% vs 5.62%; P = 0.009). (4) In men, those who had stable career, higher degree of education, regular income, had higher HUA prevalence than other cohorts. (5) people with HUA had higher plasma TC, TG, LDL, urea nitrogen and creatinine levels, higher blood pressure and higher BMI.The prevalence of HUA was lower in Kazaks in Fuhai than that in other areas in China. Males were more susceptible to HUA. diet, occupation, educational background and economic status may partly affect the prevalence of HUA in Kazaks in Fuhai.