The interleukin-17 (IL-17) family of cytokines has emerged as a critical player in autoimmune disease, including systemic lupus erythematosus (SLE). However, the role of IL-17B, a poorly understood cytokine, in the pathogenesis of SLE is still not clear. In this study, we investigated the role of IL-17B in the activation and differentiation of B cells, and the pathogenesis of SLE. Intriguingly, IL-17B deficiency aggravated disease in lupus-prone mice and promoted the activation of B cells and the differentiation of germinal center (GC) B cells and plasma cells, while recombinant mouse IL-17B (rmIL-17B) significantly alleviated disease in lupus-prone mice. Mechanistically, rmIL-17B inhibited the activation of the Toll-like receptor (TLR) and interferon (IFN) pathways in B cells by downregulating the FASN-mediated lipid metabolism. Loss of FASN significantly alleviated the disease in lupus-prone mice and inhibited the activation and differentiation of B cells. In addition, B cells had greater FASN expression and lower IL-17RB levels in patients with SLE than in healthy controls. Our study described the role of IL-17B in regulating B-cell activation and differentiation, and alleviating the onset of SLE. These findings will lay a theoretical foundation for further understanding of the pathogenesis of SLE.

Chronic graft-versus-host disease (GvHD) is the leading cause of late death in allogenic hematopoietic stem cell transplantation recipients, of which the kidney is a potential target. In this article, we report an extremely rare case of chronic GvHD, characterized by immune complex-mediated diffuse proliferative glomerulonephritis and various autoantibodies detected in the serum; it is the first case of lupus-like chronic GvHD reported to date. The patient responded well to intensive immunosuppressive therapy and reached complete remission. Mycophenolate mofetil was more effective than tacrolimus in this case, suggesting that treatment of kidney diseases associated with chronic GvHD should be based on pathogenesis and pathological patterns.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a significant modulator of inflammation in various clinical contexts, including infection, cellular stress, and tissue injury. The extensive participation of the cGAS-STING pathway can be attributed to its ability to detect and control the cellular reaction to DNAs originating from both microorganisms and hosts. These DNAs are well recognized as molecules linked with potential risks. At physiological levels, the STING signaling system exhibits protective effects. However, prolonged stimulation of this pathway contributes to autoimmune disorder pathogenesis. The present paper provides an overview of the activation mechanism of the cGAS-STING signaling pathways and their associated significant functions, as well as therapeutic interventions in the context of systemic lupus erythematosus (SLE). The primary objective is to enhance our comprehension of SLE and facilitate more effective diagnosis and treatment strategies for this condition.

The cyclic GMP-AMP synthase (cGAS), a prominent intracellular DNA sensor in mammalian cells, controls the innate immune response and the stimulator of interferon genes (STING)-mediated synthesis of pro-inflammatory cytokines, such as type-I interferon (IFN-I). For decades, IFN-I has been hypothesized to be essential in the development of systemic lupus erythematosus (SLE), a chronic multisystem autoimmunity characterized by immune complex (IC) deposition in small vessels. Recent findings revealed that the activation of the cGAS-STING pathway by self-DNA would propagate the autoimmune responses via upregulating IFN-I production in SLE. In this review, we aimed to provide a comprehensive outlook of the role of the cGAS-STING pathway in SLE pathobiology, as well as, a better understanding of current therapeutic opportunities targeting this axis.

BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients.
METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index.
RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97).
CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.

Spontaneously formed germinal centers (GCs) have been reported in most mouse models of human autoimmune disease and autoimmune patients, and have long been considered a source of somatically-mutated and thus high affinity autoantibodies, but their role in autoimmunity is becoming increasingly controversial, particularly in the context of systemic autoimmune diseases like lupus. On the one hand, there is good evidence that some pathogenic lupus antibodies have acquired somatic mutations that increase affinity for self-antigens. On the other hand, recent studies that have genetically prevented GC formation, suggest that GCs are dispensable for systemic autoimmunity, pointing instead to pathogenic extrafollicular (EF) B-cell responses. Furthermore, several lines of evidence suggest germinal centers may in fact be somewhat protective in the context of autoimmunity. Here we review how some of the conflicting evidence arose, and current views on the role of GCs in autoimmunity, outlining mechanisms by which GC may eliminate self-reactivity. We also discuss recent advances in understanding extrafollicular B cell subsets that participate in autoimmunity.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with B-cell hyperactivity. Telitacicept is a transmembrane activator, calcium modulator, and cyclophilin ligand interactor-Fc fusion protein, which can neutralize both B-cell lymphocyte stimulator and a proliferation-inducing ligand. Patients with active SLE who received telitacicept were prospectively followed at month 1, 3, 6, 9, and 12 after telitacicept initiation. Thirty-seven participants were involved and followed for 6.00 [3.00, 6.00] months. SRI-4 rate at month 6 was 44.7%. The median dosage of prednisone was decreased by 43.8% (from 10 to 5.62 mg/d) at month 6. The anti-dsDNA level was significantly decreased, while complement levels were significantly increased at month 6 from baseline. Continuously significant reductions in serum immunoglobin (Ig)G IgA, and IgM levels were also observed. Patients experienced significant decreases in the numbers of total and naive B cells, whereas memory B cells and T cell populations did not change. The number of NK cells was significantly increased during the follow-up. At month 6, 58.3% (14 out of 24) patients experienced improved fatigue accessed by FACIT-Fatigue score exceeding the minimum clinically important difference of 4. Most adverse events were mild, but one each case of severe hypogammaglobulinemia, psychosis with suicidal behavior, and B-cell lymphoma were occurred. In our first prospective real-world study, telitacicept treatment led to a significant clinical and laboratory improvement of disease activity, as well as fatigue amelioration in patients with SLE. Safety profile was favorable overall, but more studies are greatly needed.

Systemic lupus erythematosus (SLE) is an inflammatory disorder related to immunity dysfunction. The Th1 cell family including Th1 cells, transcription factor T-bet, and related cytokines IFNγ, TNFα, IL-2, IL-18, TGF-β, and IL-12 have been widely discussed in autoimmunity, such as SLE. In this review, we will comprehensively discuss the expression profile of the Th1 cell family in both SLE patients and animal models and clarify how the family members are involved in lupus development. Interestingly, T-bet-related age-associated B cells (ABCs) and low-dose IL-2 treatment in lupus were emergently discussed as well. Collection of the evidence will better understand the roles of the Th1 cell family in lupus pathogenesis, especially targeting IL-2 in lupus.

OBJECTIVE: Relationship between neuropeptide Y (NPY) serum levels, NPY genetic mutation with systemic lupus erythematosus (SLE) pathogenesis is yet to be clarified, and role of NPY in development of SLE needs elucidation.
METHODS: This study included 460 SLE patients, 472 non-SLE cases, 500 healthy volunteers. Serum NPY, matrix metalloproteinase-1 (MMP-1) and MMP-8 levels were tested by ELISA. Genotyping 7 NPY single nucleotides polymorphisms (SNPs) (rs5573, rs5574, rs16129, rs16138, rs16140, rs16147, rs16478) was obtained by Kompetitive Allele-Specific PCR (KASP) method. Pristane-induced lupus mice were treated with NPY-Y1 receptor antagonist, and histological analysis, serological changes of the mice were evaluated.
RESULTS: NPY serum concentrations were significantly increased in SLE patients when compared to that in healthy volunteers, non-SLE cases. Rs5573 G allele, rs16129 T allele, rs16147 G allele frequencies were significantly different between SLE cases and healthy controls. Rs5574 TT + TC genotypes were related to levels of IgG, C3, C4 and erythrocyte sedimentation rate, and rs16138 GG + GC genotypes correlated with SLE cases with anti-double-stranded deoxyribonucleic acid antibody (anti-dsDNA) (+). Serum MMP-1, MMP-8 concentrations were higher in SLE patients, and NPY levels were significantly related to MMP-1, MMP-8 levels. After treatment of lupus mice with NPY-Y1 receptor antagonist, damage of liver, spleen and kidney was alleviated, production of autoantibodies (anti-nuclear antibody (ANA), total IgG, anti-dsDNA) and MMP-1, MMP-8 was down-regulated, and differentiation of CD3+, CD8+ T cells, B cells, monocytes, macrophages, T helper 1 (Th1), Th2, Th17 cells was reversed.
CONCLUSIONS: NPY may be a biomarker for lupus, which may promote occurrence and development of lupus.

Chimeric antigen receptor T cell (CAR-T) therapy, an innovative immune cell therapy, has revolutionized the treatment landscape of haematological malignancies. The past 2 years has witnessed the successful application of CD19-targeting CAR constructs in refractory cases of autoimmune rheumatic diseases, including systemic lupus erythematosus, systemic sclerosis and anti-synthetase syndrome. In comparison with existing B cell depletion therapies, targeting CD19 has demonstrated a more rapid and profound therapeutic effect, enabling drug-free remission with manageable adverse events. These promising results necessitate validation through long-term, large-sample randomized controlled studies. Corroborating the role of CAR-T therapy in refractory rheumatological disorders and affirming safety, efficacy and durability of responses are the aims of future clinical studies. Optimizing the engineering strategies and better patient selection are also critical to further refining the successful clinical implementation of CAR-T therapy.