ObjectiveSystemic lupus erythematosus (SLE) is a complex autoimmune condition with diverse manifestations. Childhood-onset SLE (cSLE) presents more severely than adult-onset disease with a higher incidence of severe neurologic or renal manifestations and lower estimated survival rates. There is limited literature on the range of severe gastrointestinal manifestations at presentation in cSLE, and this lack of information results in underappreciation of these potentially life-threatening complications and little guidance regarding management of these patients.MethodsWe reviewed cases of patients with cSLE and severe GI manifestations at presentation diagnosed at our institution and additionally provide a comprehensive review of existing cases in the literature to discuss presenting symptoms, other clinical features, longitudinal course, treatment, and long-term outcomes.ResultsWe identified six cases of cSLE with primary, severe GI symptoms at time of diagnosis at our institution and an additional 25 patients who presented similarly in the literature. Severe GI manifestations included protein-losing enteropathy, thoracoabdominal aortitis, severe pancreatitis, lupus enteritis or mesenteric vasculitis, and intestinal pseudo-obstruction. Delays in diagnosis affected several patients, and 26% of patients required surgical intervention. Many patients required intensive immunomodulatory treatment in addition to prolonged bowel rest and parenteral nutrition. Long-term outcomes of GI manifestations varied overall, however, most patients at our institution achieved clinical remission.ConclusionsUnderstanding these rare cases of severe GI manifestations in cSLE can aid clinicians in prompt diagnosis and collaborative management, improving clinical outcomes for this vulnerable population.

Cutaneous (CLE) and systemic lupus erythematosus (SLE) are autoimmune diseases with a multifactorial pathogenesis. Ultraviolet radiation (UVR) is the most important trigger of CLE; however, the degree of photosensitivity varies between the clinical subtypes. The expression of matrix metalloproteinases (MMPs)-important enzymes involved in skin turnover and homeostasis-is modulated by UVR. To investigate the causality of the clinically observed effects of UVR, sun-exposed lesional skin samples from patients with different subtypes of lupus erythematosus (LE) were examined by immunohistochemistry for the expression of MMP1 and MMP28 and compared with biopsies from polymorphous light eruption (PLE) and healthy skin (HS). The expression of micro-RNAs (miR-31 and miR-150)-regulators of MMP expression and cellular metabolism-in the samples was determined by in-situ hybridization and correlated with the expression of the glucose transporter 1 (GLUT1) receptor to examine potential metabolic regulation. To assess potential UVR regulation of MMP28, we performed in vitro experiments in healthy keratinocytes and fibroblasts. MMP28 expression was differentially affected by UVA1 and UVB irradiation in keratinocytes and fibroblasts. Compared with all other LE subtypes, as well as PLE and HS samples, MMP28 expression in Chilblain LE skin showed a distinct vertical distribution, reaching as far as the upper layers of the dermis. This vertical expression pattern coincided with decreased GLUT1 levels and with increased expression of miR-31 and miR-150 in the epidermis of patients with Chilblain LE. These data provide evidence for a potential metabolic dysregulation that may play a role in the etiology of LE. Furthermore, our results suggest MMP28 as a novel complementary marker in Chilblain LE diagnosis.

Systemic lupus erythematosus is an autoimmune disease with diverse systemic manifestations, while Castleman disease is a rare lymphoproliferative disorder that often presents with systemic symptoms and can mimic autoimmune disorders. β-thalassaemia trait is a genetic disorder characterised by mild anaemia. We report the case of a young female who presented with febrile episodes persisting for 6 months, accompanied by multiple joint pain and left-sided chest pain for 3 months. Physical examination revealed pallor, generalised lymphadenopathy, splenomegaly and left-sided pleural effusion. Lymph node biopsy initially suggested Castleman disease-hyaline vascular variant. However, further evaluation led to a final diagnosis of systemic lupus erythematosus with lupus nephritis and concomitant β-thalassaemia trait. This case highlights the diagnostic challenge when multiple diseases with overlapping symptoms coexist and the importance of a comprehensive evaluation in patients with atypical presentations to avoid diagnostic overshadowing.

PurposeTo explore left atrial (LA) function in patients with systemic lupus erythematosus (SLE) and mitral regurgitation assessed by cardiac magnetic resonance imaging feature tracking (MRI-FT).MethodIn this study, 64 SLE patients (35.0 ± 12.3 years, 49 females) and 50 age- and gender-matched healthy controls (32.1 ± 11.2 years, 32 females) were analyzed. Patients with SLE were further classified into two subgroups according to mitral regurgitation defined by echocardiography: mitral regurgitation subgroup (n = 32) and non-mitral regurgitation subgroup (n = 32). All subjects underwent cardiac magnetic resonance (CMR) examination and SLE patients underwent extra laboratory testing. LA volume and strain parameters were compared among the three groups, and a correlation analysis was further performed between CMR parameters and clinical variables.ResultsPatients in both mitral regurgitation and non-mitral regurgitation subgroups showed higher LAVmin (29.15 ± 7.5, 26.22 ± 8.23 vs 21.68 ± 7.67, p = .003, .026) and LAVimin (17.44,14.9 vs 12.62, p = .002,.046) than healthy control subjects. Abnormal LA reservoir, conduit and bump strain were also observed in SLE patients (all p < .05), with more severe reservoir (p = .006, .031) and bump strain (p = .01, .033) abnormality found in mitral regurgitation subgroup. In the SLE group, LA reservoir, bump and conduit strain were significantly positively correlated with LVEF (B = 0.467, p < .001 vs B = 0.019, p = .01 vs B = 0.168, p = .001 vs B = 0.036, p < .001 vs B = 0.020, p = .024). Conduit strain (εe, SRe) was positively correlated with LAEF (B = 0.229, p = .032 vs B = 0.027, p = .008).ConclusionMRI-FT based LA parameters may be considered a helpful tool to evaluate LA function in SLE patients, and LA strain may indicate severity of the cardiac dysfunction in SLE patients.

Systemic lupus erythematosus (SLE) has been associated with gut microbiota in some studies. There is no clear evidence that cytokines act as mediators.

We first assessed the differences in gut microbiota between SLE patients and healthy controls using 16S rDNA sequencing. Subsequently, we used the summary statistics of gut microbiota, cytokines, and SLE from large genome-wide association studies. To explore the causal relationships between gut microbiota and SLE and identify potential mediating cytokines, we performed bidirectional Mendelian randomization analyses. Finally, the levels of potentially mediating cytokines were determined by ELISA.

Fecal 16S rDNA sequencing showed that there was gut microbiota disorder in SLE patients. Based on two-sample analysis, seven gut microbiota taxa were causally associated with SLE. SLE influenced the relative abundance of two gut microbiota taxa in our large-scale MR study. Mediation analyses revealed that the causal relationship between genus Lachnospiraceae UCG001 and SLE was exclusively mediated by fibroblast growth factor 19 (FGF19) levels and the causal relationship between order Lactobacillales and SLE was exclusively mediated by tumor necrosis factor receptor superfamily member 9 (TNFRSF9) levels. Elevated levels of FGF19 affected the association between the reduced relative abundance of the genus Coprobacter and SLE, mediating by a proportion of 10.64% (P = 0.030). Furthermore, ELISA showed that circulating TNFRSF9 and FGF19 levels were higher in SLE patients than healthy controls.

Our study demonstrated that there is a causal link between some gut microbiota taxa and SLE. In addition, we revealed possible mediating effects in this relationship. Key Points • We first demonstrate a causal association between gut microbiota, cytokines, and SLE comprehensively. • Our experiments also confirmed that TNFRSF9 and FGF19 may play a role in SLE. These results provide new ideas for microbiome-based investigation of new mechanisms and therapies for SLE.

The bidirectional relationship between autoimmune diseases and malignancy has been widely discussed. And the relationship between autoimmune diseases and the risk of malignancy varies. Here, we categorized and re-analyzed the evidence of the association between six autoimmune diseases and malignancy risk, in order to provide ideas for the prevention of malignancy in the long-term individualized management of patients with autoimmune diseases.

We systematically searched the relevant literatures in PubMed, Web of Science and Cochrane Library to identify and re-analyze studies methodically on the association between six autoimmune diseases and their malignancy risk. Our results showed that.

We included 34 meta-analyses including systematic lupus erythematosus, rheumatoid arthritis, psoriasis, ankylosing spondylitis, primary Sjogren's syndrome, multiple sclerosis, totalling 742 studies. Our results showed that the remaining five AIDs, with the exception of MS, were positively associated with the risk of overall malignancy. Among them, patients with SLE had the highest risk of developing lymphomas, oropharyngeal cancer and non-Hodgkin's lymphoma, and the lowest risk of developing uterine cancer, melanoma and endometrial cancer. The RA patients had the highest risk of developing lymphomas, Hodgkin's lymphoma and non-Hodgkin's and the lowest risk of colon cancer. pSS patients had the highest risk of lymphoma. MS patients had the highest risk of lung cancer and the lowest risk of testicular cancer. AS patients had the highest risk of lymphoblastic leukemia. PsO patients had the highest risk of keratinocyte cancer.

Patients with systematic lupus erythematosus, rheumatoid arthritis, psoriasis, ankylosing spondylitis and primary Sjogren's syndrome lead to an increased risk of overall malignancy, whereas patients with MS lead to a decreased risk of overall malignancy. However, the risk relationship between the same AIDs and different malignancies varied.

This study evaluated the prevalence and incidence of systemic lupus erythematosus (SLE) in Germany and explored real-world data on sequence of therapy (SOT; sequence of drugs as prescribed in clinical practice).

This retrospective, observational, longitudinal cohort study using German claims data from the WIG2 GmbH Scientific Institute for Health Economics and Health System Research database (January 2011-December 2019), extrapolated to the statutory health insurance (SHI)-insured population, evaluated prevalence and incidence in an epidemiological analysis group and SLE treatment patterns in an incident cohort (subgroup ≥ 18 years of age with incident disease and ≥ 24-month follow-up post index date). Analyses were descriptive.

Based on the epidemiological analysis (N = 3017), annual SLE prevalence per 100,000 gradually increased from 40.47 in 2012 to 59.87 in 2019 in the SHI population. In contrast, annual SLE incidence was relatively stable, ranging from 8.83 in 2012 to 8.86 in 2019. In the incident cohort (n = 941), based on SOT analysis (n = 681), treatment gaps of > 60 days were common: 67.1%, 51.2% and 54.9% in SOT1, SOT2 and SOT3, respectively. Corticosteroids were the most frequent monotherapy in SOT1 (31.0% vs 0% in SOT2/SOT3); 30.0-70.0% of patients received a corticosteroid combination therapy across SOTs. Over 50% of patients in each SOT received an antimalarial therapy (combination or monotherapies). The use of biologic disease-modifying drugs was low, ranging from 0.4% in SOT1 to 9.7% in SOT3.

Our data demonstrate an increased prevalence of SLE with stable incidence in Germany, suggesting improved survival of affected patients. Nevertheless, suboptimal treatment patterns, including limited use of biologics, reflect a high unmet need for optimised and personalised therapies in patients with SLE.

The response of the kidney after induction treatment is one of the determinants of prognosis in lupus nephritis, but effective predictive tools are lacking. Here, we sought to apply deep learning approaches on kidney biopsies for treatment response prediction in lupus nephritis. Patients who received cyclophosphamide or mycophenolate mofetil as induction treatment were included, and the primary outcome was 12-month treatment response, complete response defined as 24-h urinary protein under 0.5 g with normal estimated glomerular filtration rate or within 10% of normal range. The model development cohort included 245 patients (880 digital slides), and the external test cohort had 71 patients (258 digital slides). Deep learning models were trained independently on hematoxylin and eosin-, periodic acid-Schiff-, periodic Schiff-methenamine silver- and Masson's trichrome-stained slides at multiple magnifications and integrated to predict the primary outcome of complete response to therapy at 12 months. Single-stain models showed area under the curves of 0.813, 0.841, 0.823, and 0.862, respectively. Further, integration of the four models into a multi-stain model achieved area under the curves of 0.901 and 0.840 on internal validation and external testing, respectively, which outperformed conventional clinicopathologic parameters including estimated glomerular filtration rate, chronicity index and reduction in proteinuria at three months. Decisive features uncovered by visualization for model prediction included tertiary lymphoid structures, glomerulosclerosis, interstitial fibrosis and tubular atrophy. Our study demonstrated the feasibility of utilizing deep learning on kidney pathology to predict treatment response for lupus patients. Further validation is required before the model could be implemented for risk stratification and to aid in making therapeutic decisions in clinical practice.

Hydroxychloroquine (HCQ) is an antimalarial drug that has historically been used to treat and prevent malaria. However, its mechanism of action has not yet been fully elucidated. HCQ affects various cellular and molecular pathways through different mechanisms. HCQ has also been shown to be a disease‑improving agent for the treatment of rheumatic diseases, including systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis and primary Sjögren's syndrome. Although generally considered safe, adverse reactions have been reported with the use of HCQ and clinicians should carefully monitor patients with rheumatism when prescribing these drugs. The purpose of the present review is to strengthen the clinical use of HCQ for autoimmune diseases while highlighting the adverse effects that may occur during treatment.

Circulating cell-free DNA (cfDNA) is a large molecule that plays a central role in the pathogenesis of SLE. It is the target antigen of autoantibodies and the main component of immune complexes. Due to the large differences in the content of cfDNA detected in different studies, cfDNA cannot be used as a strong diagnostic basis for SLE at present. As an active component of cfDNA, the correlation between double-stranded DNA (dsDNA) and SLE has not been fully studied. The detection of dsDNA may provide a more accurate diagnosis and treatment basis for SLE, and the in-depth study of SLE patients is helpful to further understand the pathogenesis of SLE. Blood samples were collected from 173 SLE patients and 2970 healthy controls. The concentration of serum dsDNA was determined by fluorescence quantitative method. Propensity score matching (PSM) method was used to match 444 healthy controls and 148 SLE patients according to age and gender. Serum dsDNA levels were compared between SLE patients and matched healthy controls. At the same time, blood exosomes were extracted to explore the correlation between serum dsDNA and exosome dsDNA. As demonstrated herein, serum dsDNA levels in SLE patients were shown to be considerably higher than in healthy controls. Meanwhile, In SLE patients, serum dsDNA level was correlated with season and other clinical indicators, but not with temperature and ultraviolet. Additionally, a statistically significant connection between serum and exosome dsDNA was discovered. We also found that the gene encoding the dsDNA receptor was upregulated. The presented data suggest that detection of dsDNA is promising as a rapid and simple tool for assessing disease progression in SLE, which can help physicians and patients in disease management. The mechanism of elevated dsDNA in SLE patients requires more research.

Systemic autoimmune rheumatic diseases (SARDs) cause musculoskeletal disorders and are associated with various issues that affect the quality of life. Since the musculoskeletal system is affected, the pelvic floor muscles can also be impacted, leading to possible pelvic floor dysfunctions (PFDs). Thus, the purpose of this study was to investigate the presence of PFDs, such as urinary incontinence (UI), anal incontinence (AI), genital-pelvic pain/penetration disorder (GPPPD), and pelvic organ prolapse (POP) symptoms in women with SARDs compared to a control group composed of women without SARDs; and investigate the association between SARDs and PFDs.

An online cross-sectional survey was carried out. Using a web-based questionnaire, data on demographic and anthropometric features, PFD (UI, nocturia, AI, GPPPD, and POP), and obstetric history were gathered. For quantitative variables, the Mann-Whitney U test was used, and for categorical variables, the chi-squared test was used for comparison between groups. The association between SARDs and PFD was investigated using logistic regression analysis.

The questionnaire was completed by 326 women (224 with SARDs and 102 healthy controls). Women with SARDs reported significantly more symptoms of PFD, UI, nocturia, AI (flatus and fecal incontinence), POP, and GPPPD than healthy controls. SARDs were associated with PFD, flatus incontinence, fecal incontinence, dyspareunia, and vaginismus.

PFD was much more common in women with SARDs than in healthy women. Women with SARDs were 1.8 to 5.2 times more likely than the control group to report PFD symptoms than women without SARDs.

Dynamic changes in various forms of RNA modification are critical to the functional homeostasis of the immune system and the pathophysiology of autoimmune diseases. RNA modification-related proteins play an essential role in these processes. At present, the research methods of RNA modification in autoimmune diseases are mainly to detect the expression changes of RNA modification-related proteins in tissues or cells, but there is a lack of explorations of target RNAs and in-depth mechanisms. Considering the important role of CD4+ T cell dysfunction in the pathogenesis and progression of autoimmune diseases, the regulatory effect of abnormal RNA modification on CD4+ T cells deserves attention, which will provide a perspective for further exploring the mechanism of RNA modification in autoimmune diseases. In this Review, we discuss the abnormal RNA modification changes in patients with autoimmune diseases and highlight the effects of these abnormal changes on CD4+ T cells.

Lupus nephritis is typically treated with intravenous cyclophosphamide, which is associated with serious adverse effects. Oral mizoribine may be an alternative for induction therapy of lupus nephritis. However, large-scale, long-term, randomized clinical studies of mizoribine are lacking.

To assess the efficacy and safety of oral mizoribine vs intravenous cyclophosphamide as induction therapy for Chinese patients with lupus nephritis.

This prospective, multicenter, parallel-group, open-label, phase 3 randomized clinical trial recruited patients with class III, III+V, IV, IV+V, or V lupus nephritis aged 18 to 70 years from 40 centers in China. Inclusion criteria included 24-hour urinary protein level of 1.0 g or higher and systemic lupus erythematosus disease activity index of 8 or higher. The first patient was enrolled on November 29, 2014, and the study finished March 14, 2019. The follow-up period was 52 weeks. Data were analyzed from September 4, 2019, to January 21, 2020.

Oral mizoribine (50 mg, 3 times a day) or cyclophosphamide (6 intravenous doses at 0.5-1.0 g/m2 body surface area, with a maximum dose of 1.0 g/d) for 52 weeks plus oral glucocorticoid.

Total remission rate (complete remission rate plus partial remission rate) after 52 weeks (prespecified).

A total of 250 patients were randomized, and 243 patients (mean [SD] age, 34.6 [10.7] years, 213 women [87.7%]) were treated (123 patients [50.6%] in the mizoribine group and 120 patients [49.4%] in the cyclophosphamide group). The total remission rate at 52 weeks was 66.1% (76 of 115 patients) in the mizoribine group and 76.8% (86 of 112 patients) in the cyclophosphamide group, and the relative risk ratio (mizoribine vs cyclophosphamide) was 0.861 (95% CI, 0.729-1.016). The lower limit of this 2-sided 95% CI was greater than the noninferiority margin of 0.726, indicating that mizoribine was noninferior to cyclophosphamide. Changes in other immune parameters and kidney function were generally similar between the groups. The incidence of any treatment-related treatment-emergent adverse events was 80.5% (99 of 123 patients) in the mizoribine group and 78.7% (96 of 122 patients) in the cyclophosphamide group, and the most frequent adverse event in both groups was upper respiratory tract infection (41 patients [33.3%] and 37 patients [30.3%], respectively).

This randomized clinical trial shows that compared with intravenous cyclophosphamide, oral mizoribine was noninferior and well tolerated when used with glucocorticoid for induction therapy of active lupus nephritis. Mizoribine can be used as an alternative to intravenous cyclophosphamide as induction therapy for lupus nephritis.

ClinicalTrials.gov Identifier: NCT02256150.

This review aims to synthesize recent developments in the epidemiology of idiopathic inflammatory myopathies (IIMs), focusing on incidence, prevalence, disease classification, and clinical outcomes.

IIM is a rare group of autoimmune diseases characterized by muscle weakness and systemic involvement, with incidence rates ranging from 0.2 to 2 cases per 100 000 person-years. The role of myositis-specific autoantibodies (MSAs) in stratifying disease risk and prognosis is increasingly recognized, such as in anti-MDA5 positive DM, which is associated with a high risk of rapidly progressive interstitial lung disease. Furthermore, patients with IIM exhibit elevated risks of comorbidities, including cardiovascular disease and malignancy.

IIM diseases are complex disorders with significant health impacts, necessitating enhanced awareness and research. Improved classification and understanding of MSAs are crucial for earlier diagnosis and tailored therapeutic strategies. Continued epidemiological research is essential to elucidate underlying mechanisms and inform future interventions, ultimately aiming to enhance the quality of life and clinical outcomes for affected patients.

The role of long non-coding RNAs (lncRNAs) and their nearby messenger RNAs (mRNAs) in systemic lupus erythematosus (SLE) pathogenesis is not well understood.

High-throughput sequencing was utilized to analyze PBMCs obtained from SLE patients. Subsequently, we conducted differential analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and verification through quantitative real-time PCR (qRT-PCR). Additionally, qRT-PCR was used to analyze the levels of lncRNAs or mRNAs in transfected Raji cells.

We identified 419 differentially expressed (DE) lncRNAs and their 337 nearby DE mRNAs in SLE patients. More than 67% of the DE lncRNAs were lincRNAs and intronic_lncRNAs. The most significantly regulated nearby mRNAs in SLE patients were LTF and CIRBP, potentially involved in recurrent infection and photosensitivity. GO analysis revealed upregulation of the immune effector process term, with genes such as C1qA, C1qC, C1qB, NLRP3, and CXCL6 participating in this term and the upregulated pertussis signaling pathway. Analysis of the nearby coding genes of 88 lincRNAs indicated that XLOC_185773 had the highest number of nearby encoding genes and was negatively correlated with peripheral blood lymphocyte counts, potentially regulating HARS. Furthermore, LNC_005556, an antisense DE lncRNA, was negatively correlated with lupus nephritis occurrence and may regulate the upregulated IGLL5 in patients.

The current study provides insights into the dysregulation of lncRNAs and nearby mRNAs in SLE, highlighting potential key players in the pathogenesis of the disease.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.

Despite some study demonstrated the effectiveness of telitacicept in patients with systemic lupus erythematosus (SLE), a noticeable gap exists in real-world data. This study aimed to examine the effectiveness and safety of telitacicept in patients with SLE in the real-world.

This retrospective study enrolled patients with SLE at the Tangdu Hospital from January 2022 to January 2023. These patients were administered telitacicept at 80 mg or 160 mg dosage. The observed outcomes were changes in the SLE Responder Index 4 (SRI-4), disease activity, renal function, and immunological indicators.

Sixty-one patients were enrolled, with 60 patients completed the 24-week follow-up, and 30 completed the 52-week. The SRI-4 response rates at 4, 12, 24, and 52 weeks were 52.5%, 67.2%, 75.4%, and 80.0%, respectively. No statistically differences were observed in the SRI-4 response rates between the 80 mg and 160 mg doses at any of the time points (all p > 0.05). By 52 weeks, the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index scores were significant decreased from baseline (p < 0.001), and complement 3 and 4 levels (p = 0.001), albumin levels (p = 0.004), and the overall change in glucocorticoid dosage (p < 0.001) were all significantly increased, with all showing significant changes over time (p < 0.001). During the study, 3 (4.9%) patients experienced infection, and 1 (1.6%) developed an allergy at the injection site.

Telitacicept exhibited a highly effective and favorable safety in patients with SLE, with improved renal and hematological manifestations and facilitated a reduction in glucocorticoid medication usage.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with rare but severe cardiac manifestations, including myocarditis and pericarditis. The coexistence of SLE with sickle cell trait (SCT), an inherited hemoglobinopathy prevalent among individuals of African descent, is exceptionally rare and presents significant diagnostic challenges due to overlapping clinical features. Objective: To describe the case of an Afro-Ecuadorian male with SLE and sickle cell trait who developed an uncommon presentation of myopericarditis and pericardial effusion. Case report: A 48-year-old African American male with no prior medical history presented with persistent fever, polyarticular arthralgias, and pleuritic chest pain. Investigations revealed sickle cell trait (SCT) and myopericarditis with pericardial effusion, marking the initial manifestation of SLE. Diagnostic delays occurred due to overlapping symptoms and a family history of sickle cell disease. Laboratory findings showed elevated hemoglobin S (<50%), positive ANA (1:1280, coarse speckled pattern), and anti-Smith/RNP antibodies, meeting EULAR/ACR 2019 criteria for SLE. Cardiac MRI confirmed myopericarditis. Treatment with pulse methylprednisolone, oral prednisone, and mycophenolate mofetil resulted in clinical improvement, with stable disease control on immunomodulatory therapy during follow-up. Conclusions: This case highlights the diagnostic complexity of SLE in patients with SCT, particularly when presenting with myopericarditis as the initial manifestation. It emphasizes the importance of a comprehensive diagnostic approach and timely initiation of immunosuppressive therapy to optimize clinical outcomes. This report broadens the understanding of overlapping syndromes involving SLE and SCT.

Cutaneous lupus erythematosus (CLE) is a complex autoimmune disease often characterized by a multitude of skin findings. CLE is generally classified into three main categories: acute CLE, subacute CLE and chronic CLE. The current therapeutic guidelines for CLE include counselling patients on general measures and medication regimens. Treatment options include optimized photoprotection, avoidance of environmental triggers, corticosteroids, topical and systemic immunomodulators, and antimalarials. To date, no biologic medications (i.e. monoclonal antibodies, mAbs) are approved for CLE. The first mAb for the treatment of both systemic lupus erythematosus (SLE) and active lupus nephritis was belimumab, and was approved for these diseases in 2011 and 2020, respectively. Belimumab is a specific inhibitor of B-lymphocyte stimulator. Anifrolumab, a type I interferon receptor antagonist, was approved in 2021 for SLE. Other mAbs with different targets, including a novel biologic that inhibits blood dendritic cell antigen 2, are currently under investigation for CLE. This review will describe the general treatment landscape for CLE. Selected studies related to these various mAbs will be discussed, as well as their safety profiles and efficacies demonstrated in clinical trials. Biologic medications can potentially augment the number of treatment options for patients living with CLE.

SLE is a multifaceted autoimmune disorder with a complex pathogenesis involving genetic, environmental and hormonal factors, which converge on immune dysregulation. The T cell receptor (TCR) repertoire's role in SLE has garnered significant interest due to its potential in both diagnostics and therapeutics. Our study aimed to delineate the variances in the TCRβ repertoire between patients with SLE and healthy individuals, correlating these differences with the severity and subtypes of SLE.

We conducted an analysis of blood samples from 50 treatment-naive patients with SLE and 50 healthy donors, employing RNA extraction, high-throughput sequencing and subsequent bioinformatics analysis.

Our findings revealed significant alterations in TRBV and TRBJ gene usage frequencies, indicative of a skewed TCR repertoire in patients with SLE. Notably, nine hub TRBV genes were identified as potential biomarkers for SLE with high diagnostic accuracy. Furthermore, we observed a reduction in TCR diversity, characterised by a lower diversity 50 value and increased clonal expansion, which correlated with disease severity.

The TCRβ repertoire is significantly altered in SLE, with potential implications for diagnostics and therapeutics. The identified hub genes may serve as novel biomarkers for SLE, and the findings contribute to the understanding of the immunopathogenesis of the disease.

Systemic lupus erythematosus (SLE) is a complex and incurable autoimmune disease, so several drug remission for SLE symptoms have been developed and used at present. However, treatment varies by patient and disease activity, and existing medications for SLE were far from satisfactory. Novel drug targets to be found for SLE therapy are still needed.

Mendelian randomization (MR), an observational study way, was performed to explore potential drug targets for SLE using protein quantitative trait loci (pQTL) from recently published genome-wide association studies (GWAS) of cerebrospinal fluid (CSF) and plasma proteins, which obtained genetic instruments for 154 CSF proteins of 971 participants, and 734 plasma proteins of 23591 participants. Bidirectional Mendelian randomization analysis, colocalization analysis, and phenotype scanning were performed to find key proteins for SLE. In addition, external data verification was implemented to further consolidate the Mendelian randomization findings. Candidate proteins as targets to find drugs and discuss the druggability. Finally, Network pharmacology and molecular docking methods were used to verify the effects of Voclosporin and Cyclosporine on SLE targets. Protein-protein interaction (PPI) and core target analysis of candidate drugs and SLE overlapping targets were performed to identify potential hub targets and interactions. The affinity between drug targets and SLE targets was confirmed by molecular docking.

In the preliminary analysis, we identified four key proteins as possible drug targets in CSF and plasma proteins, included ICAM-1(P = 4.62E-05, OR = 0.90(0.86, 0.95)), sICAM-1(P = 4.62E-05, OR = 0.49(0.35, 0.69)), FCG2B (P = 7.63E-11, OR = 0.57(0.48, 0.67)), PPP3CA; PPP3R1 (P = 5.47E-07, OR = 0.66(0.57, 0.78)). Among them, ICAM1 was detected in both CSF and plasma proteins. By excluding reverse causality, confounding factors, and linkage disequilibrium (LD), we identified PPP3CA; PPP3R1 as novel drug targets for SLE, including Voclosporin and Cyclosporine. Finally, the Drugbank database shows that novel drugs contain 33 targets for treating SLE. PPI suggested that SIRT1, ACE, PTGS2, and BACE1 were pivotal targets for SLE treatment. In addition, the molecular docking showed that the bioactive molecules of Voclosporin and Cyclosporine had a good affinity with the target of SLE.

Our integrative analysis suggested that levels of circulating PPP3CA; PPP3R1 had causal effects on SLE risk and served as potential treatment targets. Moreover, this study provides new evidence for Voclosporin as an SLE treatment through Mendelian randomization and Network pharmacology, and warrants further clinical investigation.

An increasing body of evidence has revealed the association between immune-mediated inflammatory diseases (IMIDs) and sarcopenia. However, a genetically direct causality between IMIDs and sarcopenia remains elusive.

To investigate the relationship between IMIDs and sarcopenia-related traits and identify potential therapeutic targets, a Mendelian randomization (MR) was performed. We collected publicly available genome-wide association studies (GWAS) data for seven common IMIDs, including systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PSO), ankylosing spondylitis (AS), and rheumatoid arthritis (RA). Additionally, summary-level GWAS data for sarcopenia-related traits, including appendicular lean mass (ALM), left-hand grip strength, and right-hand grip strength were collected. To search for therapeutic targets, we used two types of genetic instruments to proxy the exposure of druggable genes, including genetic variants within or nearby drug targets and expression quantitative trait loci (eQTLs) of drug targets. Two-sample MR and summary-data-based MR (SMR) were used to calculate effect estimates, and sensitivity analyses were implemented for robustness. Drug tractability, gene enrichment analysis, and protein-protein interaction (PPI) analysis were used to validate the biological and clinical significance of the selected drug targets.

The two-sample MR analysis indicated the existence of casual associations between IMIDs and sarcopenia-related traits in the overall and sex-stratified populations. In particular, PSO had causal effects on decreased ALM, which showed significance in all six MR analysis tests with directional consistency in the overall population. Grounded in this robust association, HLA-DRB5, HLA-DRB1, and AGER were identified as potential therapeutic targets for ALM decline by drug target MR and further confirmed by SMR analysis. These genes were associated with therapeutic agents currently undergoing evaluations in clinical trials. Gene enrichment and PPI analysis indicated a strong association of these genes with immune functions.

This MR study contributes novel genetic evidence supporting the causal link between IMIDs and sarcopenia, with a particular emphasis on the association between PSO and decreased ALM. Additionally, AGER, HLA-DRB1, and HLA-DRB5 emerge as potential therapeutic targets for ALM decline.

Systemic lupus erythematosus (SLE) is characterized by impaired B-cell function and a distinct B-cell phenotype. Toll-like receptor (TLR) 10 is highly expressed in human B cells and can regulate B-cell activation. Here, we examined the variations in TLR10 expression across B-cell subpopulations and its impact on the disease activity in SLE patients.

Thirty-one patients with stable SLE, 30 patients with active SLE, and 28 healthy controls (HCs) were recruited. Flow cytometry was performed to assess the prevalence of B-cell subpopulations and their TLR10 expression. The diagnostic value of unswitched memory B cells (UMB) and double-negative B cells (DNB) in relation to disease activity was determined. The correlations between TLR10 expressions in B-cell subpopulations and disease activity were further evaluated, respectively.

Compared with the HCs, the stable patients exhibited significantly reduced Naive B proportion and elevated switched memory B and DNB proportion, while active patients presented markedly decreased UMB and increased DNB proportion. Furthermore, the receiver operating characteristics analysis revealed that UMB was more reliable than DNB in diagnosing SLE disease activity. Among the B-cell subsets, only the TLR10 expression in UMB was notably diminished in SLE patients, particularly in active patients. Importantly, TLR10 expression in UMB was negatively correlated with the disease activity.

UMB could serve as a promising biomarker for SLE disease activity, and the TLR10 expression in UMB was negatively correlated with the activity of SLE patients, suggesting that TLR10 might be involved in the disease progression of SLE by regulating the UMB function. Key Points • Active SLE patients exhibited reduced unswitched memory B cells and increased double-negative B cell proportions in blood. • Unswitched memory B cells are better predictors of disease activity in SLE than double-negative B cells. • TLR10 expression in unswitched memory B cells is markedly diminished in SLE patients. • TLR10 expression in unswitched memory B cells is negatively associated with SLE disease activity.

To evaluate the treatment patterns, medication adherence, concomitant corticosteroid use, factors influencing sequence of therapies (SOTs), healthcare resource utilisation (HCRU) and associated costs in adults with SLE in the USA.

Claims data from the Merative MarketScan Commercial and Medicare Supplemental Database between 2011 and 2019 were used to identify patients with incident SLE. The date of first claim with SLE was defined as the index date, with a 24-month pre-index and ≥24-month post-index period. Descriptive statistics were used to evaluate patient demographics and baseline clinical characteristics, treatment patterns, adherence, HCRU and cost. Multivariable-adjusted logistic regression models were used to identify factors associated with transition between SOTs.

Overall, 2476 patients received SLE treatment. The mean (SD) age was 46.9 (14.1) years and the mean (SD) follow-up duration was 47.8 (15.7) months. High corticosteroid use was prevalent in all SOTs (≥1 corticosteroid; average dose, 16.8-19.3 mg/day; 50%-60% patients). Antimalarials were most commonly prescribed in SOT 1 (85.7%), and immunosuppressants in SOT 2 and 3 (85.4% and 77.5%, respectively). Transition frequency from SOT 1-2 (38.4%) and SOT 2-3 (16.9%) was influenced by immunosuppressant prescription, concomitant corticosteroid use, sex, severe disease activity, non-persistence and age. Adherence was highest for biologics, followed by antimalarials and immunosuppressants. SLE-related HCRU and associated costs increased with SOT progression (mean (SD) at baseline vs SOT 3, US$19 489 (US$45 336) vs US$23 201 (US$39 628)).

SLE treatment regimens with greater adherence and reduced corticosteroid use, HCRU and associated costs are needed.

The aim of this study was to investigate lower extremity performance, balance, fatigue and pain in individuals with Systemic Lupus Erythematosus and compare them with healthy controls.

41 participants (Systemic Lupus Erythematosus n = 21 and mean age = 38.33 ± 13.37; healthy group n = 20 and mean age = 38.95 ± 12.62 years) were included in the study. Lower extremity performance was evaluated with timed up and go test and 30 s sit-to-stand test, static and dynamic balance with Sensamove Miniboard, fatigue levels with Visual Analog Scale and Fatigue Severity Scale and pain intensity with Visual Analog Scale.

Significant differences were found in favor of the healthy group in the sit-to-stand test (p = 0.001), timed up and go test (p = 0.001), static balance-center (p = 0.020), front (p = 0.001), back (p = 0.002), left (p = 0.001), right (p = 0.001); proprioception-left (p = 0.004), reaction time-front (p = 0.002) and left (p = 0.016); travel time-front (p = 0.001), back (p = 0.001), left (p = 0.001) and right (p = 0.001), Fatigue Severity Scale (p = 0.001); Visual Analog Scale-fatigue (p = 0.001) and Visual Analog Scale-pain (p = 0.001). In Systemic Lupus Erythematosus, timed up and go test had low correlation with travel time-back (r = -0.449; p = 0.041). Visual Analog Scale-fatigue had low correlation with proprioception-left (r = 0.484; p = 0.026) and proprioception-right (r = 0.461; p = 0.035). Visual Analog Scale-pain had moderate correlation with proprioception-back (r = 0.521; p = 0.015) and low correlation with proprioception-right (r = 0.441; p = 0.045).

Compared to healthy, individuals with Systemic Lupus Erythematosus had worse lower extremity performance, static/dynamic balance, fatigue, and pain. Dynamic balance-back was related to lower extremity performance. Fatigue was related to left-right proprioception, and pain was related to back-right proprioception.

Systemic lupus erythematosus (SLE), an extensive autoimmune disorder, compromises viral resistance and alters immune responses post respiratory virus vaccines. This study aims to assess immune response levels and safety in SLE patients following respiratory virus vaccines.

Extensive searches, until 1 March 2024, were conducted using PubMed, EMBASE, and Cochrane Library. Outcomes, encompassing seroconversion rate (SCR), antibody and IgG titers, neutralizing antibodies, anti-spike antibodies, anti-receptor binding domain (RBD) IgG, and adverse events, were appraised.

Sixteen articles, comprising 25 observational studies, were included. SLE patients exhibited lower SCR (OR = 0.42, 95%CI: 0.26 to 0.69), antibody titers (SMD=-2.84, 95%CI: -3.36 to -1.61), and neutralizing antibodies (OR = 0.27, 95%CI: 0.13 to 0.56) compared to the healthy population post respiratory virus vaccines. Notably, differences were statistically insignificant for anti-RBD IgG (OR = 1.75, 95%CI: 0.10 to 29.42), IgG titers (SMD=-2.54, 95%CI: -5.57 to -0.49), anti-spike antibodies (OR = 0.35, 95%CI: 0.08 to 1.53), injection site discomfort (OR = 1.03, 95%CI: 0.52 to 2.06), fatigue (OR = 1.23, 95%CI: 0.74 to 2.03), fever (OR = 1.02, 95%CI: 0.64 to 1.63), localized reactions (OR = 0.69, 95%CI: 0.37 to 1.30), systemic reactions (OR = 1.00, 95%CI: 0.59 to 1.69), allergic reactions (OR = 5.11, 95%CI: 0.24 to 107.10), self-reported vaccination-related adverse events (OR = 1.61, 95%CI: 0.56 to 4.63), and disease flares after vaccination (OR = 1.00, 95%CI: 0.14 to 7.28).

Despite the reduced immune response and host protection in SLE patients post-Corona Virus Disease 2019 (COVID-19) and influenza vaccines compared to the healthy population, safety profiles are comparable. Therefore, it is recommended that SLE patients receive COVID-19 and influenza viral vaccines to fortify their resistance.

The effect of rehmannioside A (ReA) on systemic lupus erythematosus (SLE) is not clear and needs further study. In this study, SLE-related targets were obtained from the DisGeNet and GeneCards databases, while ReA-related targets were obtained from the SwissTarget and SuperPred databases. A protein-protein interaction network of intersected targets was constructed using the STRING platform. After selecting the intersected targets, GO and KEGG enrichment analyses were performed via the R package "clusterProfiler". The relationships between ReA and various core targets were assessed via molecular docking, and molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking. The top five targets in the ranking of degree value were HSP90AA1, HIF1A, PIK3CA, MTOR, and TLR4. Significant biological processes mainly included response to oxidative stress and response to reactive oxygen species. The potential pathways of ReA in the treatment of SLE mainly focused on the PI3K-Akt signaling pathway, neutrophil extracellular trap formation, and Apoptosis. Molecular docking showed that ReA had the highest binding affinity for mTOR, suggesting that mTOR is a key target of ReA against SLE. Molecular dynamics simulations revealed good binding abilities between ReA and mTOR. In conclusion, ReA exerts its effects on SLE through multiple targets and pathways, with mTOR being a key target of ReA against SLE.

Rheumatic diseases encompass a range of entities affecting the musculoskeletal system and connective tissue due to immune dysregulation. These entities include rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis that present significant medical and social challenges by impacting individuals' quality of life and working capacity. In developing countries, where healthcare access is limited, the burden of these diseases is particularly severe. Analyzing the regional epidemiological characteristics of rheumatic diseases may enhance our understanding of risk factors and aid in developing targeted preventive measures. This study utilized data from the Republican Centre for Health Development in Kazakhstan from 2018 to 2021. The incidence of various rheumatic diseases was examined in the adult population of Shymkent, Kazakhstan, including rheumatoid arthritis, gout, osteoarthritis, systemic lupus erythematosus, dermatomyositis, scleroderma, and ankylosing spondylitis. Shymkent's total number of rheumatic disease cases rose from 52,617 in 2018 to 52,781 in 2021. Primary morbidity increased from 18,381 to 21,677 cases. Incidence rates for systemic lupus erythematosus, systemic scleroderma, and ankylosing spondylitis increased, while cases of rheumatoid arthritis and osteoarthritis showed fluctuation. Gender distribution analysis revealed that women were more frequently affected by rheumatoid arthritis and systemic lupus erythematosus whereas men were more prone to ankylosing spondylitis. The results underscore the need to tailor diagnostic and treatment approaches to account for age-and gender-specific differences in rheumatic diseases. The increased incidence of some diseases calls for new prevention and treatment strategies. This study highlights the significant burden of rheumatic diseases in Shymkent, Kazakhstan and emphasizes the importance of local epidemiological research in adapting medical practices to regional specifics.

Systemic lupus erythematosus (SLE) is an autoimmune disease, the pathophysiology and genetic basis of which are incompletely understood. Using a forward genetic screen in multiplex families with SLE, we identified an association between SLE and compound heterozygous deleterious variants in the non-receptor tyrosine kinases (NRTKs) ACK1 and BRK. Experimental blockade of ACK1 or BRK increased circulating autoantibodies in vivo in mice and exacerbated glomerular IgG deposits in an SLE mouse model. Mechanistically, NRTKs regulate activation, migration, and proliferation of immune cells. We found that the patients' ACK1 and BRK variants impair efferocytosis, the MERTK-mediated anti-inflammatory response to apoptotic cells, in human induced pluripotent stem cell (hiPSC)-derived macrophages, which may contribute to SLE pathogenesis. Overall, our data suggest that ACK1 and BRK deficiencies are associated with human SLE and impair efferocytosis in macrophages.

Systemic lupus erythematosus (SLE) affects women, with the onset of disease typically around the childbearing years.

This study examines the frequency and risk factors for adverse pregnancy outcomes (APOs) in an Australian cohort, and any disease flares during pregnancy and post partum.

Female patients with SLE enrolled in the Australian Lupus Registry and Biobank (ALRB) between January 2007 and June 2019 were studied. Self-reported pregnancy history, including adverse foetal or maternal outcomes, was collected at the time of enrolment and updated as appropriate. Baseline demographics, clinical parameters, medication exposure and disease activity were collected. Factors associated with APO were examined using univariate and multivariate logistic regression analyses.

Pregnancy history was available in 278 patients; 30% were nulliparous. Most pregnancies occurred before the diagnosis of SLE. Patients who had pregnancies after SLE diagnosis had an earlier age of diagnosis, and had fewer pregnancies. The APO rate was 44.3% in the overall cohort, with most presenting as prematurity with or without foetal growth restriction. Women with APO were also diagnosed with SLE at a younger age and had a higher prevalence of anti-cardiolipin antibodies and hypocomplementemia. Early age of SLE diagnosis was a significant independent risk factor for APO. No increase in disease flare was observed in those who experienced APO during the observation period of ALRB.

This study shows a considerable incidence of APO in patients with SLE, emphasising the need for pre-pregnancy counselling and collaboration between maternal-foetal medicine specialists and rheumatologists, especially for women diagnosed with SLE at a younger age.

The generation of representative disease phenotypes is important for ensuring the reliability of the findings of observational studies. The aim of this manuscript is to outline a reproducible framework for reliable and traceable phenotype generation based on real world data for use in the Data Analysis and Real-World Interrogation Network (DARWIN EU). We illustrate the use of this framework by generating phenotypes for two diseases: pancreatic cancer and systemic lupus erythematosus (SLE).

The phenotyping process involves a 14-steps process based on a standard operating procedure co-created by the DARWIN EU Coordination Centre in collaboration with the European Medicines Agency. A number of bespoke R packages were utilised to generate and review codelists for two phenotypes based on real world data mapped to the OMOP Common Data Model.

Codelists were generated for both pancreatic cancer and SLE, and cohorts were generated in six OMOP-mapped databases. Diagnostic checks were performed, which showed these cohorts had broadly similar incidence and prevalence figures to previously published literature, despite significant inter-database variability. Co-occurrent symptoms, conditions, and medication use were in keeping with pre-specified clinical descriptions based on previous knowledge.

Our detailed phenotyping process makes use of bespoke tools and allows for comprehensive codelist generation and review, as well as large-scale exploration of the characteristics of the resulting cohorts. Wider use of structured and reproducible phenotyping methods will be important in ensuring the reliability of observational studies for regulatory purposes.

Lupus nephritis (LN) is the most serious complication of systemic lupus erythematosus (SLE), and plasma exosomes may serve as a bridge. MicroRNAs (miRNAs) are abundant in exosomes, so this study aimed to explore the role of exosome-derived miRNA in the development of LN.

The publicly available data containing plasma exosomal miRNAs in SLE patients and healthy controls were researched, and differential expression and functional enrichment analysis of exosomal miRNA was conducted. Then, plasma exosomes from SLE patients were extracted, and the accuracy of differential expression and functional enrichment analysis was preliminarily verified. PKH26 dye was used to label exosomes to detect whether exosomes can enter HK2 cells. Evaluation of plasma exosomes impact on cell viability was done by utilizing CCK-8 assay. Flow cytometry was used to measure cell apoptosis.

Plasma exosomes were successfully extracted and identified. Through differential expression analysis of the pulbilic data and subsequent qPCR validation, we observed that miR-20b-5p is overexpressed in plasma exosomes of SLE patients, whereas miR-181a-2-3p is downregulated. Then functional enrichment analysis revealed that these differential miRNAs primarily regulate processes such as apoptosis, autophagy, and inflammation. Then, flow cytometry analysis conducted after co-incubation of plasma exosomes and peripheral blood mononuclear cells confirmed that exosomes can indeed regulate apoptosis. And plasma exosomes can successfully enter HK2 cells without affecting cell activity. In addition, plasma exosomes promote HK2 cell apoptosis and autophagy. Overexpression of miR-181a-2-3p could inhibit HK2 cells apoptosis and upregulate the expression of bcl2, and beclin1. At the same time, a trend towards increased apoptosis rates was observed in HK2 overexpressed miR-20b-5p, although the difference did not reach statistical significance. And miR-20b-5p can enhance the expression of caspase3 and becin1 while suppressing the expression of bcl2 and LC3β.

Our research indicates that the abundant presence of miR-20b-5p and the depletion of miR-181a-2-3p in plasma exosomes of SLE patients may mediate the promotion of apoptosis and autophagy in HK2 cells, thereby causing kidney damage and the development of LN.

In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients.

A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age ≥15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria.

Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01).

A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity.

Type I interferons (IFN-Is) are important players in the immunopathogenesis of systemic lupus erythematosus (SLE). Pathogenic events in patients with SLE are potent triggers of IFN-I induction, yet IFN-I may induce or initiate the immunopathogenesis leading to these events. Because blocking IFN-I is effective in some clinical manifestations of SLE patients, concerns about the efficacy of anti-IFN-I therapy in patients with lupus nephritis remain. Tissues from kidney biopsies of patients with lupus nephritis revealed infiltration of various immune cells and activation of inflammatory signals; however, their correlation with renal damage is not clear, which raises serious concerns about how critical the role of IFN-I is among the potential contributors to the pathogenesis of lupus nephritis. This review addresses several issues related to the roles of IFN-I in SLE, especially in lupus nephritis, including (1) the contribution of IFN-I to the development and immunopathogenesis of SLE; (2) evidence supporting the association of IFN-I with lupus nephritis; (3) therapies targeting IFN-I and IFN-I downstream signaling molecules in SLE and lupus nephritis; (4) findings challenging the therapeutic benefits of anti-IFN-I in lupus nephritis; and (5) a perspective associated with anti-IFN-I biologics for lupus nephritis treatment. In addition to providing clear pictures of the roles of IFN-I in SLE, especially in lupus nephritis, this review addresses the lately published observations and clinical trials on this topic.