OBJECTIVE:To investigate CD177+PMN dysregulation on endothelial cells in Behçet disease (BD), a chronic systemic vasculitis characterized by polymorphonuclear neutrophil (PMN) activation and endothelial dysfunction. METHODS:We reanalyzed BD PMN RNA-sequencing data and quantified CD177+PMN in BD peripheral (n = 38) and vascular tissue. We then analyzed BD and healthy control CD177+PMN using RNA sequencing (n = 7) and measured neutrophil extracellular trap (NET) production, which were used to stimulate vascular endothelial cells (VECs) for RNA-sequencing analysis. Differentially expressed proteins in NETs were determined by mass spectrometry. Senescence, senescence-associated secretory phenotype (SASP), and PMN chemotaxis of VECs treated with BD CD177+PMN-derived NETs were assessed. RESULTS:Transcriptome analysis revealed BD PMN overexpressed CD177. CD177+PMN subset was expanded in active and severe systemic BD and accumulated in BD aortic walls. Enhanced NETosis and oxidative phosphorylation in BD CD177+PMN were noted in RNA sequencing, which were confirmed in both resting and activated BD CD177+PMN. BD CD177+PMN-derived NETs promoted senescence, SASP, and PMN chemotaxis in VECs using RNA-sequencing analysis, which were validated by up-regulated IL-6, CXCL8, ICAM-1, p21, SA-β-gal, and cell proliferation arrest. Mass spectrometry identified that BD CD177+PMN-derived NETs contained more histone 3.1 (H3.1). H3.1 induced senescence, SASP, and PMN chemotaxis in VECs via Toll-like receptor 4 signaling, which was attenuated by senolytics. CONCLUSION:Increased CD177+PMN in patients with BD promotes senescence and SASP in VECs through secreting H3.1-enriched NETs, which recruit PMN and collectively contribute to vasculitis in BD.

Behçet's disease (BD) is a life-threatening systemic vasculitis characterized by polymorphonuclear neutrophils (PMN) and macrophage activation. However, the interaction of PMN and macrophages remains elusive. To elucidate the potential dysregulation of BD PMN exosomes on macrophage activation, PMN exosomes from both BD patients and healthy controls are isolated, quantified and incubated with macrophages. We find that BD PMN exosomes are decreased and negatively correlated with C-reactive protein (CRP). PMN exosomes can suppress IL-6, TNF, CD80 and CD86 expressions on macrophages, which are attenuated in BD PMN exosomes. In addition, by miRNA sequencing of PMN exosomes, RNA sequencing of miRNA-transfected macrophages, and dual luciferase reporter assay validation of the miRNA target, we find that miR-122-5p is decreased in BD PMN exosomes, targeting IRF5, suppressing TLR4 signaling and IFN-β autocrine, eventually downregulating macrophage activation. Our study illustrates that BD PMN exosomes are decreased in both quantity and miR-122-5p, which impairs the potential immunoregulatory effects on macrophages through degrading IRF5 and suppressing IFN-β autocrine, shedding light on the interaction mechanism between PMN and macrophages.

Primary Sjögren's syndrome (pSS) is a prevalent autoimmune disease characterized by exocrine gland dysfunction, with hallmarks of B cell and T cell overactivation, whose underlying mechanism remains largely unknown. Herein, we show that pSS plasma contained more extracellular vesicles (EVs) than HC plasma, which promoted CD4+ T cell activation, Th1, and follicular T helper cell (Tfh) differentiation, aggravating pSS immunopathology. Notably, pSS plasma EVs were enriched with miR-501-3p, mediating CD4+ T cell activation and Tfh cell differentiation. Furthermore, miR-501-3p downregulated special AT-rich sequence-binding protein-1 (SATB1) to promote Tfh differentiation. These findings suggested pSS plasma EVs as an important contributor to pSS pathogenesis, which was of potential clinical interest in managing pSS.

ABSTRACTObjectiveThis study aimed to investigate the mortality, survival rates, and prognostic indicators of cancer occurrence after Sjögren's syndrome (SS‐CA).MethodsThe medical records of patients with SS‐CA at the Peking Union Medical College Hospital (PUMCH) between January 2010 and August 2022 were retrieved. Clinical data and survival outcomes were compared to controls. The standard mortality ratio (SMR) versus the general population was calculated, and the survival and predictive markers of prognosis were analyzed using Kaplan–Meier curves and Cox regression.ResultsIn total, 114 SS‐CA patients were included, with a median follow‐up time of 105.1 (57.3–168.0) months. Non‐Hodgkin lymphoma (32, 28.1%) was the most common cancer in patients with SS‐CA. The SMR of SS‐CA patients was 2.61 (95% confidence interval [CI] 1.73–3.77). Patients with SS‐CA exhibited significantly inferior outcomes compared to controls (p = 0.010), with 5‐ and 10‐year overall survival rates of 91.2% and 83.2%, respectively. SS patients with a diagnostic interval between SS and cancer (SS‐CA diagnostic interval) ≤ 3 years or with hematological malignancies had poorer survival compared to those with a diagnostic interval > 3 years (p < 0.001) or with solid tumors (p = 0.019). Multivariate Cox regression analysis identified the prognosis‐associated factors of SS‐CA as age at SS diagnosis > 50 years (HR 3.129, 95% CI 1.224–7.998; p = 0.017), SS‐CA diagnostic interval ≤ 3 years (HR 7.754, 95% CI 1.953–30.781; p = 0.004), and hematological malignancies (HR 2.648, 95% CI 1.201–5.838; p = 0.016).ConclusionMalignant comorbidities constituted a poor prognosis in patients with SS, wherein the SS‐CA diagnostic interval and the types of cancer were associated with survival.

Objectives: Primary Sjögren's syndrome (pSS) is associated with a risk allele T of rs117026326 located at a potential splicing enhancer within the intronic region of general transcription factor II-I (GTF2I). This study aimed to explore the rs117026326-regulated alternative splicing of GTF2I and its role in B cell overactivation in pSS. Methods: GTF2I isoform expressions and rs117026326 genotypes of pSS peripheral blood mononuclear cells (PBMCs) were examined using quantitative PCR and Sanger sequencing, respectively. GTF2IΔ was overexpressed in B cells, T cells, and macrophages using plasmid transfection. Proliferation of B cells and T cells was determined using Cell Counting Kit-8 (CCK8) assay. CD4+ T cell differentiation was inspected using flow cytometry. Proinflammatory cytokine production of macrophages was investigated using quantitative PCR. c-FOS expression in GTF2IΔ-transfected B cells was tested by quantitative PCR, and proliferation of GTF2IΔ-transfected B cells treated with c-FOS siRNA or c-FOS inhibitor was interrogated using CCK8 assay. Results: pSS patients with risk allele of rs117026326 expressed higher levels of GTF2IΔ and GTF2Iζ isoforms. GTF2IΔ expression was correlated with serum immunoglobulin G (IgG). GTF2IΔ promoted B cell proliferation and upregulated c-FOS expression. Knocking down or inhibition of c-FOS reversed B cell proliferation driven by GTF2IΔ. Conclusion: pSS risk allele of rs117026326 modulates alternative splicing of GTF2I and upregulates GTF2IΔ isoform, which promotes B cell proliferation through enhancing binding and transcription of c-FOS.

Extrahepatic manifestations in patients with primary biliary cholangitis (PBC) are frequently observed recently. We aimed in this study to explore the clinicopathological characteristics and prognosis of glomerulonephritis in patients with PBC. Consecutive PBC patients admitted to Peking Union Medical College Hospital from January 2002 to May 2019 were retrospectively enrolled. PBC patients with other autoimmune diseases which may have nephritis were excluded. Structured interview, systemic rheumatologic examination, and laboratory tests were conducted for each patient. Literature about patients with PBC and glomerulonephritis was reviewed and summarized. Among the 330 PBC patients enrolled, glomerulonephritis were identified in 10 patients (3.0

To explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-β signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.

Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren ‘s syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod’s unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.

Iguratimod (IGU) reduces hypergammaglobulinemia and disease activity in pSS (primary Sjögren’s syndrome) patients. However, the therapeutical mechanism of IGU for pSS remains largely unknown. This study aimed to investigate the regulation of Tfh cell differentiation by IGU in pSS patients. We prospectively enrolled 13 pSS patients treated with IGU for 3 months and examined circulating T cell and B cell subsets by flow cytometry. We measured Tfh cell differentiation treated by IGU in pSS patients and healthy controls. Transcriptome analysis combined with molecular docking were employed to identify potential therapeutical targets of IGU, which were verified by Western blot and Tfh cell differentiation. Tfh, plasmablast, and plasma cells were suppressed by IGU treatment at 1 and 3 months. Tfh cell differentiation and function were significant inhibited by IGU in pSS patients and healthy controls in vitro. Pyruvate dehydrogenase kinase 1 (PDK1) was identified as a target of IGU during Tfh cell differentiation, and the downstream Akt phosphorylation was attenuated by IGU. Moreover, the activity of mTORC1 and phosphorylation of STAT3 were suppressed by IGU, with downregulation of BCL6 and upregulation of PRDM1. Finally, Akt activator restored IGU-suppressed Tfh cell differentiation. IGU suppresses Tfh cell differentiation in pSS patients through interacting with PDK1 and suppressing Akt-mTOR-STAT3 signaling.

AIM:To verify the role of CX3C chemokine ligand 1 - CX3C chemokine receptor 1 (CX3CL1-CX3CR1) pathway in the pathogenesis of primary biliary cholangitis (PBC). To explore whether CCL26, a novel functional ligand to CX3CR1, participates in the immunological mechanism of PBC.METHODS:Fifty-nine PBC patients and 54 healthy controls were recruited. Enzyme-linked immunosorbent assay and flow cytometry were used to measure CX3CL1 and CCL26 concentrations in plasma and CX3CR1 expression on peripheral lymphocytes, respectively. Chemotactic effects of CX3CL1 and CCL26 toward lymphocytes were detected by Transwell cell migration assays. CX3CL1 and CCL26 expressions in liver were assessed by immunohistochemical staining. Effects of CX3CL1 and CCL26 on stimulating cytokine production from lymphocytes were evaluated using intracellular flow cytometry.RESULTS:Significantly elevated CX3CL1 and CCL26 plasma concentration and CX3CR1 expression on CD4+ and CD8+ T cells were noted in PBC patients. CX3CL1 exhibited chemotactic activity toward CD8+ T, natural killer (NK) and NKT cells in a dose-dependent manner while such chemotactic effects were not detected for CCL26. In PBC patients, CX3CL1 and CCL26 were both increasingly expressed in biliary tracts and a concentration gradient of CCL26 in hepatocytes around portal areas was observed. Immobilized CX3CL1 could enhance interferon-γ production from T and NK cells while such effect was not exhibited by soluble CX3CL1 or CCL26.CONCLUSIONS:CCL26 expression is significantly elevated in plasma and biliary duct of PBC patients, yet does not appear to attract CX3CR1-expressing immune cells. CX3CL1-CX3CR1 pathway promotes the infiltration of T, NK and NKT cells into bile ducts and forms a positive feedback loop with T-helper 1 type cytokines in PBC.

Background: Behçet's disease (BD) is a systemic vasculitis characterized by hyperactivation of polymorphonuclear neutrophil (PMN) that overproduce proinflammatory cytokines and neutrophil extracellular traps (NETs).Methods: Focusing on immunometabolism, we comprehensively analyzed serum metabolomics and peripheral immune cell transcriptomics in BD patients and sex- and age-matched healthy controls (HC). We further intervened on critical enzymes of mevalonate pathway to elucidate that metabolite farnesyl pyrophosphate (FPP) is the key metabolite involved in BD-PMN hyperactivation. We measured the levels of FPP in PMN and serum, correlated them with BD disease activity, and assessed FPP-induced PMN and vascular endothelial cell activation. We also explored the calcium-dependent pathway and key BD serum cytokine to reveal the underlying mechanism of FPP-induced PMN activation.Findings: We discovered that the mevalonate pathway is dysregulated in PMN from BD patients, and the levels of FPP is significantly upregulated. Remarkably, FPP levels in both PMN and serum are positively correlated with disease activity in treatment-naïve BD patients. Furthermore, extracellular FPP functions as a metabolic endogenous danger signal, inducing PMN to produce proinflammatory cytokines and NETs, thereby exacerbating vascular endothelial inflammation and damage. Mechanistically, these events are dependent on TRPM2-calcium signaling pathway. Notably, elevated serum TNF-α, but not IL-6, IL-18, IL-1β or IFN-γ, potently upregulated TRPM2 expression on PMN, intensifying its responsiveness to FPP and exacerbating the proinflammatory microenvironment in BD. Significantly, TNF-α inhibitor therapy effectively downregulated TRPM2 expression on PMN in BD patients.Interpretation: Our study unravels the proinflammatory implications of FPP in fueling BD-PMN hyperactivation, broadening research on hyperactivated PMN-induced autoinflammatory diseases from an immunometabolism perspective. It also highlights a novel therapeutic mechanism of TNF-α inhibitors in BD and other autoinflammatory disorders.Funding: This work was mainly supported by National Natural Science Foundation of China [grant number 82371822, 82171800].Declaration of Interest: The authors declare no conflict of interests.Ethical Approval: he PUMCH Ethical Committee approved this study (1-23PJ1123), and all subjects provided written informed consent.

Behçet's disease (BD) is a systemic vasculitis characterized by neutrophil activation with unclear pathogenesis. This study aimed to explore the transcriptional profiles of BD neutrophils and identify specific gene signatures. We performed RNA sequencing on neutrophils from treatment-naive active BD patients and healthy controls, then analyzed differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) and transcription regulatory network. Quantitative real-time PCR and Western Blot were used to validate chemotaxis-related DEGs expression. We detected 567 DEGs, including 520 upregulated genes and 47 downregulated genes. 9 KEGG pathways were enriched, dominated by the NF-κB pathway and chemotaxis. The transcription regulatory network suggests ETS1 regulated the enhanced chemotaxis of BD neutrophils. Validation experiments demonstrated the overexpression of ETS1, CCR6 and CCL5 in BD neutrophils compared with HC, and ETS1 was significantly increased in vascular BD compared with other BD subgroups. Our study revealed increased activation and chemotaxis of BD neutrophils characterized by the overexpression of CCL5, CCR6 and ETS1.

Behçet’s disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. However, a comprehensive understanding of immune disturbances in BD and how they contribute to BD pathogenesis is lacking. Here, we performed single-cell and bulk RNA sequencing to profile peripheral blood mononuclear cells (PBMCs) and isolated monocytes from BD patients and healthy donors. We observed prominent expansion and transcriptional changes in monocytes in PBMCs from BD patients. Deciphering the monocyte heterogeneity revealed the accumulation of C1q-high (C1qhi) monocytes in BD. Pseudotime inference indicated that BD monocytes markedly shifted their differentiation toward inflammation-accompanied and C1qhimonocyte–ended trajectory. Further experiments showed that C1qhimonocytes enhanced phagocytosis and proinflammatory cytokine secretion, and multiplatform analyses revealed the significant clinical relevance of this subtype. Mechanistically, C1qhimonocytes were induced by activated interferon-γ (IFN-γ) signaling in BD patients and were decreased by tofacitinib treatment. Our study illustrates the BD immune landscape and the unrecognized contribution of C1qhimonocytes to BD hyperinflammation, showing their potential as therapeutic targets and clinical assessment indexes.

Abstract Objective To investigate the clinical features of multicentric reticulohistiocytosis (MRH). Methods The clinical manifestations, laboratory examination results and histologic characteristics of eleven patients with MRH were collected and compared with those of 33 patients with rheumatoid arthritis. Results In total, 72.7% of the MRH patients were women. The median age was 46 years (range 33–84 years). Diagnosed by specific pathologic features, all MRH patients exhibited cutaneous involvement. The dorsa of the hands, arms, face and auricle were the most commonly affected areas. Nodules were also located on the legs, scalp, trunk, neck, and even the hypoglossis and buccal mucosa. Ten MRH patients (90.9%) had symmetric polyarthritis. Compared with rheumatoid arthritis (RA) patients, MRH patients were more likely to have distal interphalangeal joint (DIP) involvement (63.6% vs 24.2%, P = 0.017) and less likely to have elbow (36.4% vs 72.7%, P = 0.003), ankle (45.5% vs 93.9%, P < 0.001) and metacarpophalangeal joint (MCP) (36.4% vs 78.8%, P = 0.009) involvement. Positivity for rheumatoid factor (RF) (36.4% vs 84.6%, P = 0.001) and anti-CCP antibody (9.1% vs 81.8%, P = 0.000), as well as the median RF titer [43.8 (31.7–61.0) vs 175.4 (21.3–940.3), P = 0.021], in MRH patients was lower than in RA patients. Elevation of the erythrocyte sedimentation rate (ESR) was also less common in MRH patients than in RA patients (36.4% vs 72.7%, P = 0.030). After treatment with median- to large-dose corticosteroids and disease-modifying antirheumatic drugs, 8 patients achieved complete remission and 2 patients partial remission (skin lesions ameliorated, joint lesions not ameliorated). Conclusion Always pathologically diagnosed, MRH is a systemic disease involving RA-like erosive polyarthritis and a specific distribution of skin nodules characterized by "coral beads". More DIP involvement and less elbow, ankle and MCP involvement are seen in MRH than in RA. In addition, less positivity and lower-titer RF, uncommon presence of anti-CCP antibodies and ESR elevation may be helpful to distinguish MRH from RA.

Objectives Enhancer of zeste homolog 2 (EZH2) is an epigenetic regulator that plays an essential role in immune system development and autoimmune diseases. This study aimed to characterize the role of EZH2 in the pathogenesis of primary Sjögren’s syndrome (pSS). Methods We analyzed EZH2 expression in two transcriptomic datasets of peripheral blood mononuclear cells (PBMCs) from pSS patients and healthy controls. We measured EZH2 expression in CD4+ T cells, CD8+ T cells, and CD19+ B cells from pSS patients and healthy controls and correlated EZH2 expression with clinical parameters. We also examined the activation, proliferation, and T-cell differentiation of CD4+ T cells using the EZH2 inhibitor GSK126, EZH2 siRNA, and EZH2-expressing vector. We further examined the STAT3 signaling pathway after EZH2 inhibition and detected Tfh differentiation in EZH2-overexpressed CD4+ T cells with STAT3 knocked down. Results EZH2 was upregulated in GSE164885 and GSE48378. EZH2 expression was higher in pSS CD4+ and CD8+ T cells, and EZH2 expression in circulating pSS CD4+ T cells was positively correlated with IgG, IgA, ESR, RF, and the circulating Tfh population. EZH2 inhibition and silencing EZH2 suppressed activation, proliferation, and Tfh differentiation. Furthermore, overexpressing EZH2 promoted activation, proliferation, and Tfh differentiation in CD4+ T cells. EZH2 inhibition attenuated STAT3 phosphorylation in CD4+ T cells. STAT3 knockdown abrogated EZH2-promoted Tfh differentiation. Conclusions EZH2 expression was abnormally elevated in pSS CD4+ T cells, which facilitated Tfh differentiation of CD4+ T cells by enhancing STAT3 phosphorylation. EZH2 promotes Tfh differentiation and might be implicated in pSS pathogenesis.

Background Macrophages are key innate immune cells implicated in the pathogenesis of Behçet’s disease (BD), and macrophage polarization plays a pivotal role in inflammatory response. This study aimed to investigate the role of BD serum on the phenotypes and functions of macrophage polarization. Methods BD or HC serum-treated human monocyte-derived macrophages (HMDMs) were examined M1/M2 phenotypes using flow cytometry and ELISA. The phagocytic capacity of HMDMs and CD4 + T cell differentiation facilitated by HMDMs were measured by flow cytometry. Transcriptome analysis of BD and HC serum-stimulated HMDMs was conducted to identify differentially expressed genes. NF-κB signaling was examined using western blot to explore the mechanism of macrophage polarization induced by BD serum. Results BD serum-treated macrophages expressed a higher level of CD86, IL-12, and TNF-α and a lower level of CD163, which were compatible with the M1-like phenotype. Furthermore, BD serum-treated macrophages showed enhanced phagocytic capacity and promoted more Th1 cell differentiation. Sixty-one differentially expressed genes were identified between BD and HC serum-treated macrophages and were enriched in NF-κB signaling. BD serum-treated macrophages showed upregulated p-p65 and downregulated IκBα, and NF-κB inhibitor attenuated BD serum-stimulated M1-like phenotype. Conclusions BD serum promoted macrophage polarization toward a proinflammatory M1-like phenotype through NF-κB signaling and potentially facilitated inflammation in BD. M1 polarized macrophages may be a potential therapeutic target for BD.

Autoimmunity refers to the phenomenon that the body's immune system produces antibodies or sensitized lymphocytes to its own tissues to cause an immune response. Immune disorders caused by autoimmunity can mediate autoimmune diseases. Autoimmune diseases have complicated pathogenesis due to the many types of cells involved, and the mechanism is still unclear. The emergence of single-cell research technology can solve the problem that ordinary transcriptome technology cannot be accurate to cell type. It provides unbiased results through independent analysis of cells in tissues and provides more mRNA information for identifying cell subpopulations, which provides a novel approach to study disruption of immune tolerance and disturbance of pro-inflammatory pathways on a cellular basis. It may fundamentally change the understanding of molecular pathways in the pathogenesis of autoimmune diseases and develop targeted drugs. Single-cell transcriptome sequencing (scRNA-seq) has been widely applied in autoimmune diseases, which provides a powerful tool for demonstrating the cellular heterogeneity of tissues involved in various immune inflammations, identifying pathogenic cell populations, and revealing the mechanism of disease occurrence and development. This review describes the principles of scRNA-seq, introduces common sequencing platforms and practical procedures, and focuses on the progress of scRNA-seq in 41 autoimmune diseases, which include 9 systemic autoimmune diseases and autoinflammatory diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.) and 32 organ-specific autoimmune diseases (5 Skin diseases, 3 Nervous system diseases, 4 Eye diseases, 2 Respiratory system diseases, 2 Circulatory system diseases, 6 Liver, Gallbladder and Pancreas diseases, 2 Gastrointestinal system diseases, 3 Muscle, Bones and joint diseases, 3 Urinary system diseases, 2 Reproductive system diseases). This review also prospects the molecular mechanism targets of autoimmune diseases from the multi-molecular level and multi-dimensional analysis combined with single-cell multi-omics sequencing technology (such as scRNA-seq, Single cell ATAC-seq and single cell immune group library sequencing), which provides a reference for further exploring the pathogenesis and marker screening of autoimmune diseases and autoimmune inflammatory diseases in the future.

Objective To evaluate the safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases. Methods Relevant literature was retrieved from the PubMed database, Embase database, Cochrane Library database, etc. The search period is from the establishment of the database to January 2022. The outcomes include clinical symptoms, improvement in biochemistry, improvement in intestinal microbiota, improvement in the immune system, and adverse events. Literature screening and data extraction were independently carried out by two researchers according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for statistics and analysis. Results Overall, a total of 14 randomized controlled trials (RCTs) involving six types of autoimmune diseases were included. The results showed the following. 1) Type 1 diabetes mellitus (T1DM): compared with the autologous fecal microbiota transplantation (FMT) group (control group), the fasting plasma C peptide in the allogenic FMT group at 12 months was lower. 2) Systemic sclerosis: at week 4, compared with one of two placebo controls, three patients in the experimental group reported a major improvement in fecal incontinence. 3) Ulcerative colitis, pediatric ulcerative colitis, and Crohn’s disease: FMT may increase clinical remission, clinical response, and endoscopic remission for patients with ulcerative colitis and increase clinical remission for patients with Crohn’s disease. 4) Psoriatic arthritis: there was no difference in the ratio of ACR20 between the two groups. Conclusion Based on current evidence, the application of FMT in the treatment of autoimmune diseases is effective and relatively safe, and it is expected to be used as a method to induce remission of active autoimmune diseases. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235055 , identifier CRD42021235055.

OBJECTIVE:Frequent relapse is a prominent challenge in managing immunoglobulin G4-related disease (IgG4-RD). According to the types of organs involved in relapse, relapse patterns were divided into recurrent organ involvement (ROI) and new organ involvement (NOI). We aimed to investigate the discrepancy in clinical relapse patterns and establish an effective prognostic nomogram for NOI. METHODS:We retrospectively enrolled 125 IgG4-RD patients who experienced relapse during the follow-up period. Patients were classified into two groups: those with NOI (including NOI and NOI + ROI) and without NOI (ROI). Logistic regression analyses were used to assess the risk factors for NOI. The results were externally validated by a separate prospective cohort of 39 patients with relapse. RESULTS:There were 81 (64.8%) and 44 (35.2%) patients without NOI and with NOI, respectively. Patients without NOI showed higher baseline disease activity. The most common ROIs were the lacrimal gland and submandibular gland, while the lung and urinary system were the most involved in NOI. Re-elevation of serum IgG4 level to 74.31% of baseline was associated with NOI. Multiple relapses, organ involvement type at baseline, glucocorticoids combined with immunosuppressive drugs (IM) or IM alone during the maintenance period, and relapse IgG4/baseline IgG4 ratio were included in the nomogram. Both internal and external validations showed good agreement and discrimination. CONCLUSIONS:About one third of IgG4-RD patients with relapse suffer from NOI. We developed a risk stratification model that can effectively predict the future risk of NOI. Glucocorticoid and IM combined therapy during maintenance is also recommended.