Background/Objectives: Autophagy plays a role in systemic lupus erythematosus (SLE) pathogenesis. Nevertheless, the specific genetic determinants underpinning this process remain poorly characterized. Summary data-based Mendelian randomization (SMR) analysis was therefore utilized to pinpoint autophagy-related genes associated with SLE risk. Methods: We analyzed 700 autophagy-related genes, integrating methylation quantitative trait loci (mQTL), expression QTL (eQTL) from blood and relevant tissue, and protein QTL (pQTL) data with genome-wide association studies (GWAS) data on SLE from the IEU dataset (discovery). GWAS data from FinnGen and the GWAS Catalog were used as replication datasets. Colocalization analysis identified shared genetic variants. Blood samples from 10 healthy control and 20 SLE patients were collected and analyzed for the expression of candidate genes. Results: Our SMR analysis identified suggestive associations between NLRP6 expression (OR = 0.528, 95%CI = 0.291-0.96) and p27Kip1 protein abundance (OR = 0.269, 95%CI = 0.08-0.904) with SLE susceptibility in the discovery cohort, supported by colocalization evidence. Additionally, we found that the methylation of the NLRP6 promoter (cg06432119) was significantly increased, while NLRP6 expression and p27Kip1 level were significantly decreased in SLE patients compared to controls. Furthermore, NLRP6 mRNA expression was significantly negatively correlated with the SLE severity (SLEDAI-2000). Conclusions: These findings not only prioritized candidate genes via SMR analysis but also provided evidence of epigenetic dysregulation of NLRP6 and its correlation with disease activity in SLE, thereby offering novel insights into the underlying mechanisms.

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by multi-organ damage, a complex interplay of immune dysregulation, and antibodies against nuclear macromolecules like DNA. Among these, anti-dsDNA antibodies are not only crucial diagnostic markers but also active participants in disease pathogenesis, forming immune complexes that deposit in various tissues and trigger inflammation. Emerging research has highlighted the critical role of Deoxyribonuclease 1-Like 3 (DNASE1L3), a secreted endonuclease, in maintaining homeostasis of cell-free DNA (cfDNA). Deficiencies or dysfunction of DNASE1L3, whether due to genetic mutations or neutralizing autoantibodies, lead to impaired clearance of cfDNA derived from apoptotic cells, microparticles, and Neutrophil Extracellular Traps (NETs). This accumulation of cfDNA plays an important role in SLE. This review explores the characteristics of DNASE1L3, the current status of research on the mechanisms through which its defects contribute to SLE pathogenesis, and its promising potential in the clinical diagnosis, monitoring, and treatment of this complex disease.

OBJECTIVES:This study aims to evaluate the safety and efficacy of anti-B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells in treating refractory lupus nephritis (LN). METHODS:This is an open-label, single-arm clinical trial assessing anti-BCMA CAR T cells in treating refractory LN patients. CAR T cells were infused following lymphodepletion therapy with cyclophosphamide and fludarabine. Patients were regularly followed up, in which clinical assessments were performed and laboratory indices were collected. Repeated renal biopsies and single cell RNA sequencing in certain patients were performed to help evaluate the therapeutic efficacy. The primary endpoints were the safe dosage of single infusion and the occurrence of adverse events, while the secondary endpoints focused on the therapeutic efficacy (eg, changes of Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2000]). RESULTS:Seven biopsy-confirmed LN patients were enrolled in this study with a median follow-up of 9 months, whose peripheral B cells were effectively eliminated within the first month postinfusions and restored within 3 months except one patient. Hypogammaglobulinemia was frequently observed in this study. Only one case of grade 1 cytokine release syndrome was noted, and no immune effector cell-associated neurotoxicity syndrome or severe infection was reported. SLEDAI-2K scores decreased from a median of 18 (range 10-22) at baseline to 0 (range 0-4) at the last follow-up, and 5 out of 7 patients achieved definition of remission in systemic lupus erythematosus (DORIS) complete remission. Decreased deposition of immune complex, reduced clonal abundance, and alleviated proinflammatory status of peripheral lymphocytes were also observed in repeated renal biopsy and transcriptomic analyses,. CONCLUSIONS:Anti-BCMA CAR T therapy can help LN patients inducing and maintaining disease remission status safely and effectively, which indicated the potential feasibility of the BCMA-only-targeting strategy in treating autoimmune diseases with abnormal humoral immune responses through CAR products.

Background:Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune dysregulation, heterogeneous clinical phenotypes, and a complex interplay of pathogenic mechanisms. RNA-binding proteins (RBPs), which orchestrate post-transcriptional gene regulation through dynamic interactions with target transcripts, are increasingly implicated in autoimmune pathogenesis. However, the cell-type-specific heterogeneity of RBPs expression and their regulatory networks in SLE remain poorly characterized. Methods:To delineate RBPs dynamics in SLE skin microenvironment, we conducted a comprehensive single-cell transcriptomic analysis of publicly accessible single cell RNA sequencing (scRNA-seq) datasets from lesional skin biopsies of SLE patients and healthy controls (HC). Cell-type-specific RBPs expression patterns were systematically profiled across epidermal keratinocytes, dermal endothelial cells, and T cells. Complementary bulk RNA-Seq analyses employing Splicing Site Usage Variation Analysis (SUVA) were performed to identify immune gene-associated regulatory alternative splicing (RAS) events. Integrative co-expression networks linking RBPs, RAS events, and immune pathways were subsequently constructed. Results:Single-cell resolution revealed marked heterogeneity in RBPs expression across keratinocyte, endothelial cell, and T cell in SLE compared to HC. Notably, disease-specific RBPs were enriched in pathways governing interferon response, cytokine signaling, and leukocyte activation. Cross-analysis with bulk transcriptomic data highlighted JUN and HLA-A as hub regulators exhibiting elevated expression in SLE T cells. Network modeling further uncovered coordinated interactions between JUN, HLA-A, and RAS events in immune genes, implicating their synergistic roles in modulating T cell effector functions. Conclusion:Our multi-omics integration identifies JUN and HLA-A as central coordinators of alternative splicing programs in SLE T cells. These molecular hubs, embedded within immune regulatory networks, may drive pathogenic rewiring of T cell responses in SLE.

Objective. We sought to investigate the effectiveness of the Janus kinase 1/3 inhibitor (JAK1/3i) tofacitinib (TOF) in treating Blau syndrome (BS), and to explore the association between various clinical and genetic features and therapeutic responses within the cohort. Methods. A 5-year, multicenter, retrospective, observational study (ClinicalTrials.gov: NCT06688838) was conducted across 7 centers, focusing on genetic profiles and the clinical manifestations of the cohort. Genetic analysis, including whole-exome sequencing and nucleotide-binding oligomerization domain 2 (NOD2) and signal transducer and activator of transcription 3 (STAT3) rs2293152 phenotypic comparisons, was performed to assess therapeutic responses. Results. All patients had arthritis, with 2 cases being oligoarticular and 22 polyarticular. The joints primarily affected included the wrists, proximal interphalangeal joints, ankles, and knees. Radiographic analysis revealed symmetrical nonerosive arthropathy in 92.3% of patients. Notably, two-thirds of the cohort displayed previously unrecognized dysplastic bone changes. Ocular involvement was observed in all patients. Notably, no association was found between different NOD2 sequences and therapy response. Conversely, patients harboring the STAT3 rs2293152 GG polymorphism demonstrated favorable responses to treatment, regardless of whether JAK1/3i or tumor necrosis factor inhibitors (TNFi) were used. Conclusion. TOF could be an effective therapeutic option for patients with BS who demonstrate resistance to TNFi or corticosteroids. Specifically, the STAT3 rs2293152 GG polymorphism was associated with improved response to treatment, suggesting a genotype-influenced therapeutic efficacy.

Objective To investigate the effectiveness of the JAK 1/3 inhibitor tofacitinib in treating Blau syndrome and explore the association between various clinical and genetic features and therapeutic responses within the cohort. Methods A five-year, multi-center, retrospective, observational study was conducted across seven centers, focusing on genetic profiles and the clinical manifestations of cohort. Genetic analysis, including whole exome sequencing and NOD-2 and STAT3 rs2293152 phenotypic comparisons, was performed to assess therapeutic responses. Results Baseline data for the cohort, with a median disease duration of 9.3 years. All patients exhibited arthritis, with 2 cases being oligoarticular and 22 polyarticular. The median joint count involved was 6, primarily affecting wrists, proximal interphalangeal joints, ankles, and knees. Radiographic analysis revealed symmetrical non-erosive arthropathy in 92.3% of patients. Notably, two-thirds of the cohort displayed previously unrecognized dysplastic bone changes. Ocular involvement was observed in all patients. Notably, no association was found between different NOD-2 sequences and therapy response. Conversely, patients harboring the STAT3 rs2293152 GG polymorphism demonstrated favorable responses treatment, regardless of whether JAK1/3 inhibitors or TNF-α inhibitors were used. Conclusion Tofacitinib could be an effective therapeutic option for BS patients who demonstrate resistance to TNF-α inhibitors or corticosteroids. Specifically, the STAT3 rs2293152 GG polymorphism was associated with improved response to treatment, suggesting a genotype-influenced therapeutic efficacy.

Anti-dsDNA antibodies are pathogenically heterogeneous, implying distinct origins and antigenic properties. Unexpectedly, during the clinical and molecular characterization of autoantibodies to the endonuclease DNase1L3 in patients with systemic lupus erythematosus (SLE), we identified a subset of neutralizing anti-DNase1L3 antibodies previously catalogued as anti-dsDNA. Based on their variable heavy-chain (V H ) gene usage, these antibodies can be divided in two groups. One group is encoded by the inherently autoreactive V H 4-34 gene segment, derives from anti-DNase1L3 germline-encoded precursors, and gains cross-reactivity to dsDNA – and some additionally to cardiolipin – following somatic hypermutation. The second group, originally defined as nephritogenic anti-dsDNA antibodies, is encoded by diverse V H gene segments. Although affinity maturation results in dual reactivity to DNase1L3 and dsDNA, their binding efficiencies favor DNase1L3 as the primary antigen. Clinical, transcriptional and monoclonal antibody data support that cross-reactive anti-DNase1L3/dsDNA antibodies are more pathogenic than single reactive anti-dsDNA antibodies. These findings point to DNase1L3 as the primary target of a subset of antibodies classified as anti-dsDNA, shedding light on the origin and pathogenic heterogeneity of antibodies reactive to dsDNA in SLE.

Background and objectives: Hepatic stellate cell (HSC) activation is the cardinal factor due to the accumulation of extracellular matrix proteins during the development of liver fibrosis. The aim of the present study was to find new targets for developing drugs to treat liver fibrosis, by screening the key genes involved in the activation of hepatic stellate cells. Methods: Differentially expressed genes were identified through TCGA database. RT-PCR, immunohistochemistry (IHC) assay, western blot, and ELISA were performed to evaluate the expression levels of FAT10 and fibrotic molecules. In vitro experiments were conducted to investigate the signaling pathways and biological functions of FAT10 in LX-2 cell lines. Results: In the present study, expression profiles obtained from the Gene Expression Omnibus (GEO) were used to explore the different genes expression between HSCs treated with or without carbon tetrachloride (CCl4). Human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10) was selected for further investigations. In animal model of carbon tetrachloride-induced liver fibrosis, the expression of FAT10 on activated HSCs is upregulated. In vitro, silencing FAT10 reduced TGF-β1-induced ECM activation and accumulation in LX-2 cells, and also suppressed the inflammatory response of LX-2 cells. Further Transwell results suggested that knockdown of FAT10 could inhibit TGF-β1-induced LX-2 cell migration and invasion. Mechanistically, FAT10 promotes its fibrotic activity through regulating sirtuin 1 (SIRT1), with a concomitant activation of ECM. Conclusions: These findings indicated an unexpected role of FAT10 in liver fibrosis development, suggesting that silencing FAT10 might represent a new strategy for the treatment of fibrotic liver diseases.

风湿病具有多系统受累、临床表现多样的特点，发病隐匿、病程长、但也可表现为急性呼吸衰竭、急性肾功能不全、癫痫大发作等急性起病。本研究报道ANCA相关性血管炎合并流行性出血热1例和SLE合并脑裂头蚴病1例，分析2例疾病的诊治经过，总结经验以期提高对风湿性疾病合并传染病的认知。

DNase1L3 deficiency is an inborn error of immunity that causes monogenic systemic lupus erythematosus (SLE) in humans. Here, we identified that one third of patients with sporadic SLE have antibodies to DNase1L3. Like DNase1L3 deficiency, we found that patients with anti-DNase1L3 antibodies have features associated with immune pathways activated by immunogenic self-DNA, including elevated antibodies to dsDNA and prominent expression of the interferon and myeloid/neutrophil signatures. Interestingly, 40-80% of anti-DNase1L3 antibodies in SLE serum contain the 9G4 idiotype, which is encoded by the autoreactive heavy-chain gene segment VH4-34. Sequence and functional analysis of four anti-DNase1L3 monoclonal antibodies generated from SLE patients experiencing disease-associated flares showed that these antibodies were derived from self-reactive 9G4+ switched memory B cells. These antibodies are highly enriched in somatic hypermutations, indicating that they originated from antigen-experienced cells, and have neutralizing activity against DNase1L3. Together, the data demonstrate that autoantibodies to DNase1L3 phenocopy pathogenic mechanisms associated with DNase1L3 deficiency. Moreover, the finding that autoreactive B cells bearing the 9G4 idiotype produce dominant serum autoantibodies, including antibodies to DNase1L3, underscores VH4-34+ B cells as sensible therapeutic targets for specific depletion of pathogenic B cells in SLE.

Objectives: Systemic autoinflammatory disease (SAID) is a rare systemic auto-inflammatory and progressive disorders. There have been some reports with various therapies in SAID patients. The objective of this study is to describe the chareatercis of four cases of NAIDs benefiting from JAK 1/2 inhibitor baricitinib.Methods: We reported the four cases with SAID including two cases of Blau syndrome, one case of FMF and one case of FCAS3 syndrome. These four different patients were either resistant to currently available therapies or biologics were unaccessible during COVID-19 pandemic. We also conducted a systematic literature review about the current therapies of SAID.Results: Although genetically and phenotypically different, four cases of SAID that were treated with single use baricitinib 4 mg per day achieved improvement over eight weeks. We further identified 132 manuscripts providing more than 100 cases of SAID. Among these patients, 24 underwent biological treatments and 22 of them recovered. In these 132 manuscripts, 2 underwent JAK 1/3 inhibitor tofacitinib treatment and recovered fully.Conclusions: Case series study on the use of Jak inhibitor agents have yielded positive results in our study. For SAID patients baricitinib may be a better choice compared to injection biological treatments.

Abatacept is a CTLA-4Ig fusion protein that selectively modulates the CD80/CD86:CD28 costimulatory pathway required for full T-cell activation. The FDA has approved it to be used to treat adult rheumatoid arthritis, juvenile idiopathic arthritis, and adult active psoriatic arthritis. Considering the vital pathogenic role of the CTLA-4 pathway in autoimmune diseases, abatacept could efficiently treat other systemic rheumatic diseases. Here we reviewed the published literature to profile the perspectives about the off-label uses of abatacept, especially in those refractory cases with inadequate responses to conventional therapies and biologic agents. Abatacept can be a promising therapeutic option and contribute to reducing hormone dependence and correlated adverse events.

Background Since the first diagnosed case of infection with the novel coronavirus (SARS-CoV-2), there has been a rapid spread of the disease with an increasing number of cases confirmed every day, as well as a rising death toll. An association has been reported between acute kidney injury (AKI) and mortality in patients infected with SARS-CoV-2. Therefore, our study was conducted to explore possible risk factors of AKI as well as whether AKI was a risk factor for worse outcome, especially mortality among patients with coronavirus disease (COVID-19). Methods We included all hospital admissions with confirmed or clinically diagnosed COVID-19 from January 29 to February 25, 2020. We collected demographic and epidemiological information, past medical history, symptoms, laboratory tests, treatments, and outcome data from electronic medical records. A total of 492 patients with diagnosed or clinically diagnosed COVID-19 were included in this study. Results The prevalence rate of AKI was 7.32%. Among the factors associated with AKI, males versus females (aOR 2.73), chronic kidney disease (aOR 42.2), hypertension (aOR 2.82), increased leucocytes (aOR 6.08), and diuretic use (aOR 7.89) were identified as independent risk factors for AKI among patients infected by SARS-CoV-2. There was a significant difference in hospital fees and death in patients with and without AKI (p < 0.05). The mortality rate in patients with AKI was 63.9%. Conclusions AKI was widespread among patients with COVID-19. The risk factors of AKI in COVID-19 patients included sex, chronic kidney disease, hypertension, infection, and diuretic use. AKI may be associated with a worse outcome, especially mortality in COVID-19 patients.

OBJECTIVE:The clinical features of rheumatic patients with coronavirus disease 2019 (COVID-19) have not been reported. This study aimed to describe the clinical features of COVID-19 in rheumatic patients and provide information for handling this situation in clinical practice.METHODS:This is a retrospective case series study. Deidentified data, including gender, age, laboratory and radiological results, symptoms, signs, and medication history, were collected from 2326 patients diagnosed with COVID-19, including 21 cases in combination with rheumatic disease, in Tongji Hospital between 13 January and 15 March 2020.RESULTS:Length of hospital stay and mortality rate were similar between rheumatic and non-rheumatic groups, while the presence of respiratory failure was more common in rheumatic cases (38% vs 10%, p<0.001). Symptoms of fever, fatigue and diarrhoea were seen in 76%, 43% and 23% of patients, respectively. There were four rheumatic patients who experienced a flare of rheumatic disease during hospital stay, with symptoms of muscle aches, back pain, joint pain or rash. While lymphocytopaenia was seen in 57% of rheumatic patients, only one patient (5%) presented with leucopenia in rheumatic cases. Rheumatic patients presented with similar radiological features of ground-glass opacity and consolidation. Patients with pre-existing interstitial lung disease showed massive fibrous stripes and crazy-paving signs at an early stage. Five rheumatic cases used hydroxychloroquine before the diagnosis of COVID-19 and none progressed to critically ill stage.CONCLUSIONS:Respiratory failure was more common in rheumatic patients infected with COVID-19. Differential diagnosis between COVID-19 and a flare of rheumatic disease should be considered.TRIAL REGISTRATION NUMBER:ChiCTR2000030795.

Objectives This study aims to compare the platelet distribution width (PDW) level in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH) with that in patients with systemic lupus erythematosus alone (SLE-non-PAH) and to evaluate the clinical value of the PDW level in the early diagnosis of SLE-PAH. Patients and methods We analyzed 80 SLE-PAH patients (1 males, 79 females; 34.9±12.3 years; range, 19 to 77 years) and 154 sex- and age-matched SLE-non-PAH patients (4 males, 150 females; mean age 36.7±12.4 years; range, 19 to 69 years) hospitalized between June 2011 and April 2018. All patients underwent transthoracic Doppler echocardiography within three months of inclusion in the study. Age, sex, disease course, currently prescribed medications, clinical manifestations, and past history were collected. Pulmonary artery systolic pressure, ejection fraction, white blood cell count, red blood cell count, hemoglobin, platelet count, PDW, mean platelet volume, erythrocyte sedimentation rate, complement 3 (C3), and C4 levels were also obtained. Results The PDW level was higher in the SLE-PAH group than that in the SLE-non-PAH group (p=0.023). SLE patients were allocated into high systemic lupus erythematosus disease activity index (SLEDAI) group (SLEDAI score, ≥10) (n=121) or low SLEDAI group (SLEDAI score, <10) (n=113). The PDW level was significantly higher in the high SLEDAI group than that in the low SLEDAI group (p=0.030). The receiver operating characteristic curve was used to evaluate the clinical value of the PDW level in diagnosing PAH in SLE patients. The PDW level was valuable for diagnosing PAH in SLE patients [area under the curve (AUC)=0.591, p=0.023]. The optimal critical value of the PDW level was 14.55 fL. Under these conditions, the sensitivity, specificity, and Youden index were 57%, 63% and 0.20, respectively. For newly diagnosed patients, the PDW level had good diagnostic accuracy, with an AUC of 0.626 (p=0.037). The optimal critical value of the PDW level was 14.65 fL. Under these conditions, the sensitivity, specificity, and Youden index were 66%, 67% and 0.33, respectively. Conclusion The PDW level is a good predictor of SLE-PAH, and this parameter is applicable to various clinical settings.

JAK-STAT通路是多种细胞因子信号传导的重要途径,参与细胞增殖、分化、凋亡和免疫调节等多种生理过程,以维护机体的稳态.研究发现,JAK-STAT通路在多种疾病中参与细胞因子信号的病理传导,与癌症、血液系统疾病、消化系统疾病和免疫性疾病等的发病机制相关.该通路已成为研究银屑病关节炎(PsA)发病机制和治疗的热点.文章综述了JAK-STAT信号通路在PsA中的研究进展.

BackgroundAn outbreak of coronavirus disease 2019 (COVID-19) started in December, 2019. The epicentre, Wuhan in Hubei Province, was in lockdown. From Jan 23, 2020, most hospitals in Wuhan only focused on patients with COVID-19, and patients with chronic diseases could not visit their physicians in clinic and had no access to prescriptions. Smart System of Disease Management (SSDM) is a series of mobile applications for chronic disease management that includes both patient and physician interfaces. After training in clinic, patients regularly do a disease activity assessment, and input data from lab tests as well as their medication. The data is then synchronised to the mobile of the responsible physician. The physician can then do an online consultation and renew prescriptions on the basis of real-time data from his or her patients. We aimed to establish the feasibility and effects of SSDM in maintaining effective interactions between patients and physicians in Hubei province during the COVID-19 epidemic period.MethodsBased on the SSDM database, we did a multicentre retrospective cohort study of patients with rheumatic disease in Hubei province in China. SSDM had been widely used across China since 2015. To study the influence of interruption of routine care by the COVID-19 epidemic for patients with rheumatic disease, we included patients registered with SSDM from Hubei Province. Data on patient disease activities, online consultations, and prescription refilling, as well as surveys on satisfaction about the online service were extracted from Jan 23, 2020 to Feb 27, 2020, acting as the study group, and data from the same period during 2018 and 2019 were also extracted as a control. Inclusion criteria included a confirmed diagnosis of rheumatic disease and disease duration of at least 3 months. Patients were excluded from the study if they declined participation or discontinued before completion of the survey. For patients with rheumatoid arthritis, achieving a disease activity score with 28 joints (DAS28) of less than 3·2 was considered to be a treat-to-target (T2T) status. For patients with systemic lupus erythematosus, a disease activity index-2000 (SLESAI-2K) score of less than 4 was the main target of the lupus low disease-activity state (LLDAS). We compared the T2T and LLDAS prevalence during the epidemic period of 2020 with that of 2018 and 2019. All statistical analyses were done with Python version 3.7.4. We used descriptive and frequency statistics (percentage) to describe baseline demographic information and clinical information. Comparison of ratio variables between two groups was done with a χ2 test.FindingsBy Feb 27, 2020, a total of 173 560 adult patients (46 861 [27%] men and 126 699 [73%] women) with rheumatic disease from 860 hospitals across China registered and routinely used SSDM since 2015. Patients were encouraged to upload their data and do a disease activity self-assessment every 1–3 months. 10 441 (6%) of 173 560 patients (3237 [31%] with rheumatoid arthritis and 1566 [15%] with systemic lupus erythematosus) were managed by 176 rheumatologists from 42 hospitals in Hubei province. From Jan 23, 2020 to Feb 27, 2020, 69 rheumatologists from 28 hospitals provided 1451 patients with 1692 consultations and supplied 566 (39%) of them with continued medication, which included 55 commonly used therapeutic drugs for rheumatic diseases. 247 (8%) of 3237 patients with rheumatoid arthritis during the 2020 epidemic and 350 (9%) in same period during 2018 and 2019 did the DAS28 self-assessments, and T2T was 47% in 2020 compared with 50% in 2018 and 2019, (p=0·53). 293 (19%) of 1566 patients with systemic lupus erythematosus in 2020 and 210 (16%) in 2018 and 2019 did the SLESAI-2K self-assessments, and LLDAS was 60% in 2020 compared with 47% in 2018 and 2019 (p=0·03). Surveys showed that 100% of patients were satisfied with the interactions, which prevented the risk of cross-infection and discontinuation of medication.InterpretationPatients with rheumatism can maintain accessibility to good care in the era of the COVID-19 epidemic by using SSDM for consultations and medication refills. The clinical outcomes, at least for both rheumatoid arthritis and systemic lupus erythematosus, are not compromised.FundingNone.

Interstitial lung disease (ILD) accounts for the major cause of morbidity and mortality in rheumatoid arthritis (RA). However, little is known of the pathogenesis, diagnosis and treatment of RA-associated ILD. In this review, we describe our present understanding and ongoing research in RA-ILD. Its aetiology does appear to associate with anti-cyclic citrullinated peptide antibodies, MUC5B mutation and smoking. Another focus of this article is on recent diagnostic methods in RA-ILD. Compared with other methods, high-resolution computed tomography (HRCT) imaging is a main method for the evaluation of ILD in RA patients. Pulmonary function is better suited for assessing progression. An important topic relates to therapeutic intervention. Disease-modifying anti-rheumatic drugs (DMARDs) in RA lack strong evidence in the onset or worsening of ILD. The available literature support that methotrexate, leflunomide, abatacept and rituximab play beneficial roles in the prevention and treatment of RA-ILD.

OBJECTIVES:A case control study was conducted to evaluate the possible influence of P2RX7 single nuclear polymorphism and P2X7 receptor activity in the susceptibility of SLE with pericarditis in Chinese Han population. METHODS:We studied a cohort of SLE patients with (SLE+PCS) or without (SLE-PCS) history of pericarditis and demographic, therapeutic and clinical data were retrospectively collected. P2RX7 489 C>T (His155Tyr) genotype of each subject was analysed and classified as CC or C>T (CT and TT) variant. After isolation of peripheral blood mononuclear cells and macrophages from whole blood by centrifugation on Ficoll gradient, in vitro macrophage releases of IL-1β and IL-18 primed by LPS were evaluated by cytometric bead array. NLRP3 expression were evaluated by western blot after normalisation of house-keeping gene α-Tubulin. Finally, P2X7 receptor activity was analysed after stimulation with agonist ATP, by measuring permeability changes using ethidium bromide (EB) uptake fluorescent probe. The Hardy-Weinberg Equilibrium (HWE) analysis was used to detect the association of P2RX7 489C>T SNP with SLE complicated with pericarditis. Spearman linear regression analysis was performed to evaluate the association of macrophages uptake of EB and NLRP3 expression. RESULTS:In total 68 SLE+PCS patients and 72 SLE-PCS patients from the cohort were enrolled. No significant differences in demographic, disease activity and serological features were found between the two subgroups. The HWE analysis detected a significant positive association between SLE+PCS and the 489 C>T SNP (OR=0.65, 95%CI (0.46-0.92), p=0.03). No association was found in SLE-PCS patients carrying either genotype CC or C>T. It was shown that in vitro inflammasome-dependent IL-1β/IL-18 release from macrophages was higher in SLE+PCS patients compared to SLE-PCS, especially in those bearing the C>T variant genotype, and consequently the WB analysis ofNLRP3 expression in SLE+PCS patients bearing C>T genotype was significantly higher compared to the other genotype carriers (F=13.1, p<0.01). We also detected that macrophages of SLE+PCS patients carrying SNP 489C>T showed a higher EB uptake in response to ATP than subjects carrying wild type (CC). The Spearman linear regression analysis showed a significant association of macrophages EB uptake and NLRP3 expression as well as its dependent IL-1β and IL-18 in SLE+PCS subjects carrying SNP 489 C>T. CONCLUSIONS:Our results suggest that 489 C>T polymorphism of the P2RX7 gene is associated with activation of inflammasome NLRP3 and an increased release of IL-1β and IL-18. The EB uptake increase in macrophages of LE+PCS subjects carrying 489C>T displays the functional upregulation of P2RX7, which may be involved in the pathogenesis of SLE complicated with pericarditis in the presence of P2RX7 SNP 489C>T.