BackgroundIn genome-wide association studies (GWAS), the strong association of ABCG2 rs2231142 variant with hyperuricemia and gout was confirmed in Asian population. Additionally, the obesity, diet, lifestyle, genetics and underlying comorbidities are important risks factors predisposing to hyperuricemia and gout. The systematic reviews revealed a significant link between obesity, systemic comorbidities and hyperuricosuria for predisposition of kidney stones (nephrolithiasis). However, whether ABCG2 plays an important role in the phathogenesis of nephrolithiasis remain unclear. The interaction between genetic factors and other risk factors of nephrolithiasis is still elusive.ObjectivesIn this study, we want to explore the association between ABCG2 rs2231142 variant and the risk of nephrolithiasis in modern Taiwanese population, and clarify the role of uric acid in nephrolithiasis formation.MethodsThis retrospective case-control study was conducted using the Taiwan Biobank database. A total of 120,267 individuals of Taiwanese Han Chinese aged 30-70 years were enrolled in the study. The primary outcome was the incidence of self-reported nephrolithiasis. Odds ratio (OR) of incident nephrolithiasis was analyzed by multiple logistic regression models and the interaction between ABCG2 rs2231142 variants, serum uric acid level, on the nephrolithiasis was explored. The multifactorial confounding factors for prediction of nephrolithiasis were also re-examined in our study.ResultsFinally, we identified 8,410 participants with nephrolithiasis and the prevalence was 11.52% and 4.37% in men and women, respectively. Older age (OR=1.08, 95% CI: 1.02-1.03, p<0.001) and male gender (OR=2.21, 95% CI: 2.08-2.36, p<0.001) showed an independent predictor for development of incident nephrolithiasis. The risk of nephrolithiasis markedly increased resulting from the interaction of ABCG2 rs2231142 and nephrolithiasis. In comparison with GG genotype, the risk of nephrolithiasis also demonstrated a significant association with TT and GT genotype (TT: OR=1.18, 95% CI: 1.09-1.28, p<0.001; GT: OR=1.12, 95% CI: 1.06-1.18, p<0.001). The variant comorbidities significantly associated with susceptibility to nephrolithiasis are hyperlipidemia (OR=1.40, 95% CI: 1.29-1.51, p<0.001), hypertension (OR=1.67, 95% CI: 1.57-1.78, p<0.001), diabetes mellitus (OR=1.16, 95% CI: 1.06-1.26, p=0.002), and hyperuricemia (OR=1.06, 95% CI: 1.04-1.08, p<0.001) with significant difference. The interaction of lifestyles and the risk of nephrolithiasis revealed significant differences in smoking (OR=1.15, 95% CI: 1.09-1.22, p<0.001) and overweight (OR=1.22, 95% CI: 1.15-1.28, p<0.001) rather than alcohol use(OR=0.92, 95% CI: 0.84-1.01, p=0.083). Participants with regular physical exercise is a protective factor from nephrolithiasis (OR=0.95, 95% CI:0.9-1.0, p=0.048).ConclusionOur study demonstrated the risk of nephrolithiasis is significant association with ABCG2 rs2231142 variants. This risk also increased with systemic comorbidities (hyperlipidemia, hypertension, diabetes mellitus, and hyperuricemia), and lifestyle (obesity, and smoking). Regular physical exercise is associated with protective factor for incident nephrolithiasis.Table 1.Adjusted Odds ratio of kidney stone.VariableOR95% CIp-valueAge, years1.03(1.02-1.03)<0.001Gender female1.00—— male2.21(2.08-2.36)<0.001ABCG2 rs2231142 GG1.00—— GT1.12(1.06-1.18)<0.001 TT1.18(1.09-1.28)<0.001Hyperlipidemia No1.00—— Yes1.40(1.29-1.51)<0.001Hypertension No1.00—— Yes1.67(1.57-1.78)<0.001Diabetes No1.00—— Yes1.16(1.06-1.26)0.002Hyperuricemia >7.0 mg/dL No1.00—— Yes1.06(1.04-1.08)<0.001Smoking No1.00—— Yes1.15(1.09-1.22)<0.001Alcohol use No1.00—— Yes0.92(0.84-1.01)0.083Regular physical exercise No1.00—— Yes0.95(0.90-1.00)0.048Overweight, BMI ≥24 kg/m2 No1.00—— Yes1.22(1.15-1.28)<0.001OR was adjusted for all variables in table.Disclosure of InterestsNone declared

BackgroundAn autoimmune disease that causes inflammation and bone and cartilage deterioration is rheumatoid arthritis (RA). In the pathogenesis of RA, oxidative stress and pro-inflammatory cytokines are important factors. The main polyphenol in black tea, theaflavins (TFs), has been used medically to treat a variety of inflammatory illnesses by reducing inflammation and reactive oxygen species (ROS)ObjectivesThe medications available to treat RA have a variety of side effects. The current study was designed to assess the anti-arthritic properties of theaflavin in a mouse collagen-induced arthritis model.MethodsIn order to induce arthritis in DBA/1 mice, type II collagen was administered intradermally. From days 21 through days 42, different doses of theaflavin (50 and 100 mg/kg/day) were orally administered. To determine the effect of theaflavin on collagen-induced arthritis, histological analyses were conducted. In addition, the generation of reactive oxygen species (ROS), nitric oxide, and the activities of enzymatic antioxidants (superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase) in the joint homogenate of mice were examined. The levels of TNF-, IL-6, and IL-1β were also measured by ELISA to detect inflammation.ResultsOur results showed anti-oxidant and anti-inflammatory effects of theaflavin in arthritic mice. Histopathological studies corroborated the anti-arthritic properties of theaflavin. The compound was found to be effective in lowering ROS and nitric oxide levels while increasing enzymatic antioxidant levels. Theaflavin therapy also reduced TNF-, IL-6, and IL-1β levels.ConclusionIn mice with arthritis, theaflavin was successful in reducing inflammation and oxidative stress. These results suggest that theaflavin may be used in conjunction with other treatments to manage RA.Figure 1.TF ameliorated the severity of arthritis in CIA mouse models. (a) Representative photographs depicted the swollen and reddened rear paws of four animal groups 42 days following the initial vaccination. (b) Accumulated clinical arthritis scores in each leg ranged from 0 to 4 and were evaluated every three days using a visual scoring system. The changes in body weight of normal control or CIA mice treated with or without TF or vehicle were recorded every three days till day 42. (c) TNF-, IL-6, and IL-1 inflammatory cytokine protein levels in arthritic mouse hind paw tissues. On day 42, CIA in DBA/1 mice hind paw homogenates were taken from the normal control, vehicle-treated, or TF-treated (50 or 100 mg/kg) groups of mice. The cytokine profiles were measured using ELISA according to the techniques given. ** p < 0.01 and * p < 0.05 showed statistically significant differences in two-way ANOVA compared with the vehicle-treated CIA groupREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundSeveral studies have demonstrated immunogenicity after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD) [1], but the differences between mRNA-based and vector vaccines and the cellular responses to COVID-19 vaccines according to distinct immunogenicity in AIRD patients are still unclear.ObjectivesTo investigate the differences in efficacy and safety between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with AIRD, and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) by single-cell RNA sequencing (scRNA-seq).MethodsFrom September 16 to November 15, 2021, we consecutively enrolled 243 participants aged ≥20 years with AIRD who received COVID-19 vaccination, of whom 113 were immunized with AZD1222 and 130 with mRNA-1273. The level of serum IgG antibodies to the SARS-CoV-2 receptor-binding domain on the spike protein S1 subunit was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells were isolated from two RA patient with high anti-SARS-CoV-2 IgG level and four RA patients with low level for scRNA-seq and cell-cell communication signal was analyzed by CellChat.ResultsThe anti-SARS-CoV-2 IgG seropositivity rate was 78.8% (89/113) for AZD1222 and 83.1% (108/130) for mRNA-1273. The level of anti-SARS-CoV-2 IgG was higher in patients who received mRNA-1273 than in those who received AZD1222 (β: 30.15, 95% CI: 11.67-48.63, p=0.002) (Table 1). Prednisolone-equivalent dose >5 mg/day and methotrexate (MTX) use in AIRD patients, and non-anti-tumor necrosis factor (TNF)-α biologics and Janus kinase (JAK) inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibody level, and enriched pathways related to antigen presentation via major histocompatibility complex class II (MHC class II) were found (Figure 1). HLA-DRA and CD4 interaction was vigorous among all identified MHC-II pathway and was enhanced in high anti-SARS-CoV2-IgG antibody group.Table 1.Multivariate analysis of anti-SARS-CoV-2 IgG level in patients with rheumatic diseases following COVID-19 vaccinesMultivariate analysisβ95% CIp valueMedicationsGlucocorticoidsNot usedReference≤5 mg/day−22.48(−56.33,11.37)0.192>5 mg/day−23.45(−43.54,-3.36)0.022Methotrexate−24.89(−45.70,-4.08)0.019Targeted therapiesTargeted therapies group Not usedReference TNF inhibitor−15.78(−41.33,9.76)0.224 Non-TNF bDMARD−25.27(−55.47,4.93)0.100 JAK inhibitor−17.08(−47.23,13.07)0.265VaccineChAdOx1 nCoV-19/AZD1222ReferencemRNA-127330.15(11.67,48.63)0.002TNF: tumor necrosis factor, bDMARDs: biologic disease-modifying antirheumatic drugs, JAK: Janus kinase.Figure 1.The comprehensive cell atlas of PBMC of RA patients with high and low anti-SARS-CoV2-IgG antibodies. A) UMAP visualization of PBMC cells from RA patients. B) The proportion of cell types between high and low antibody groups. C) Volcano plot of CD16-monocyte showed differential expressed genes. D) Pathway analysis between high and low antibody groups; PRBC: peripheral blood mononuclear cell, RA: rheumatoid arthritis, NK cell: natural killer cell, pDC: plasmacytoid dendritic cell, CLP: common lymphoid progenitor.ConclusionmRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in patients with AIRD. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.References[1]Geisen UM, Berner DK, Tran F, et al. Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort. Ann Rheum Dis. 2021;80:1306-1311.AcknowledgementsThe authors thank the Biostatistics Task Force of Taichung Veterans General Hospital for their assistance with the statistical analysis in this study.Disclosure of InterestsNone declared