In South Korea, belimumab is indicated for patients with systemic lupus erythematosus (SLE), including paediatric patients aged ≥ 5 years, and for adults with lupus nephritis, based on clinical trial evidence; however, real-world data in this population remain limited. To assess the real-world safety and effectiveness of intravenous (IV) belimumab administered in patients with SLE in South Korea. This observational study (GSK Study 216984) enrolled patients with active SLE and patients with lupus nephritis across 18 South Korean institutions (July 2021–February 2023). Patients received on-label IV belimumab plus standard therapy (antimalarials, glucocorticoids and immunosuppressants). Data were collected for a minimum of 48 weeks as part of routine clinical practice (July 2021–March 2024). Safety was assessed by monitoring the incidence of adverse events (AEs), adverse drug reactions (ADRs), serious AEs (SAEs)/ADRs and AEs of special interest (including psychiatric events) and summarised descriptively. Changes in SELENA-SLEDAI scores, laboratory biomarkers and glucocorticoid dosage from baseline to week 24 or 48 were tested using the Wilcoxon signed-rank test. Of 126 enrolled patients, 105 were eligible for the ≥ 48-week safety evaluation (completed ≥ 24 weeks of belimumab treatment). Patients were mostly female (91.4

Sjögren syndrome (SS), traditionally regarded as a sicca-predominant condition, is now recognized as a systemic autoimmune disease characterized by type I interferon activation, B-cell hyperactivity, and periepithelial lymphocytic infiltration. This conceptual shift has prompted changes in terminology, with “SS” increasingly replaced by “Sjögren disease (SjD)” and “secondary SS” by “associated SjD,” reflecting the concept of polyautoimmunity and ensuring equal clinical standing. In this review, we trace the historical evolution of SS classification criteria and examine their limitations in real-world clinical practice. Current classification criteria employ a weighted scoring system incorporating objective measures, including anti-Ro antibodies, salivary gland histopathology, and exocrine function tests. However, their diagnostic application in routine care is constrained by spectrum bias, clinical heterogeneity, the presence of mimickers, and shared clinical features with other autoimmune diseases. Over-reliance on serological markers, driven by their accessibility, may further contribute to misdiagnosis. We highlight that accurate diagnosis requires flexible clinical reasoning and contextual interpretation beyond rigid adherence to classification criteria. Individualized diagnostic strategies should integrate demographics, laboratory findings, salivary ultrasonography, and histopathology. Practical challenges in diagnosing and evaluating disease activity in associated SjD are also discussed.

BACKGROUND:Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by dysregulated Th17 cell responses and osteoclastogenesis. While metformin has shown potential in autoimmune modulation, its efficacy is often limited by high dosage requirements. In this study, we evaluated the therapeutic efficacy and underlying molecular mechanisms of SD282, a newly synthesized biguanide derivative, in treating RA. METHODS:The anti-arthritic effects of SD282 were assessed using a collagen-induced arthritis (CIA) mouse model. Murine and human immune cells were used to investigate the impact of SD282 on Th17/Treg differentiation, STAT3 signaling, mitochondrial respiration (OCR), and osteoclastogenesis. RESULTS:SD282 treatment significantly ameliorated the clinical severity of CIA, reducing joint inflammation, cartilage damage, and bone erosion. At the cellular level, SD282 effectively inhibited Th17 differentiation and IL-17 production while promoting Foxp3 + Treg cells, thereby restoring immune homeostasis. Mechanistically, SD282 blocked STAT3 phosphorylation and normalized mitochondrial metabolic activity by enhancing OXPHOS complex potential. Furthermore, SD282 suppressed osteoclast differentiation by downregulating RANKL, MMP9, and NFATC1 signaling pathways. CONCLUSION:Our findings demonstrate that SD282 acts as a potent multi-target agent that suppresses RA progression by synergistically regulating the STAT3-Th17-Mitochondria axis and bone metabolism. SD282 represents a promising pharmacological candidate for the treatment of autoimmune arthritis with a superior mechanistic profile compared to conventional biguanides.

To identify risk factors and outcomes of macrophage activation syndrome (MAS) in febrile patients with systemic lupus erythematosus (SLE), and to compare clinical characteristics between MAS occurring at initial SLE diagnosis and during established disease. We retrospectively reviewed medical records of SLE patients admitted to Seoul St. Mary’s Hospital between 1990 and 2025 and identified those with MAS. Age- and sex-matched febrile SLE patients without MAS were selected as controls in a 1:3 ratio. Clinical and laboratory variables were compared, and logistic regression analysis was performed to determine factors associated with MAS. Among 1,512 febrile SLE patients, 54 (3.6

This study aimed to describe the clinical characteristics of patients with progressive pulmonary fibrosis (PPF) in systemic sclerosis (SSc)-associated interstitial lung disease (ILD) and to explore factors associated with PPF. Medical records of patients with SSc who visited Seoul St. Mary’s Hospital between April 2015 and March 2025 were retrospectively reviewed. PPF in SSc-ILD was defined as a relative decline in predicted forced vital capacity (FVC) ≥ 10

BackgroundSjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, leading to impaired glandular secretion. To elucidate the pathogenic mechanisms underlying SS, suitable preclinical animal models are essential. In this study, we developed a humanized murine model that captures key immunopathological features of SS patients, and assessed its therapeutic utility.MethodsPBMCs obtained from SS patients were stimulated with anti-CD3 and anti-CD28 antibodies for 15 hours, and 1 × 106 or 2 × 106 of these cells were intraperitoneally injected into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. At 5 weeks after cell injection, pathological analysis and immunophenotypic characterization of infiltrating immune cells within the salivary gland tissues were performed. To evaluate the efficacy of metformin, NSG mice transplanted with PBMCs were orally administered metformin daily for 5 weeks.ResultsMice injected with PBMCs from SS patients exhibited a significant increase in the frequency of human IL-17-producing T cells in the spleen, accompanied by enhanced infiltration of these pro-inflammatory cells into the salivary glands. Histopathological analysis of salivary glands revealed marked immune cell infiltration and a significant reduction in Aquaporin-5 expression in SS-derived PBMC-injected mice. Notably, these pathological changes were associated with the local recruitment of CXCR3+ Th17 cells. Metformin treatment significantly attenuated salivary gland inflammation, reduced the infiltration of pathogenic T cells, and mitigated molecular-level tissue damage in this humanized SS model.ConclusionsThe humanized murine model developed in this study effectively reproduced key cellular and molecular features of SS and provided a useful preclinical platform for investigating early-stage disease mechanisms and evaluating novel therapeutic strategies for SS.

Abstract Sjögren’s syndrome (SS) is a chronic autoimmune disease in which inflammatory cells infiltrate the exocrine glands, reducing glandular secretory function and ultimately resulting in keratoconjunctivitis sicca (dry eyes) and xerostomia (oral dryness). Cardiovascular risk factors are more prevalent in patients with SS than in healthy controls; patients with SS and metabolic syndrome also have higher leptin and inflammatory cytokine levels. In this study, we investigated the effects of HGR4113, a structural analogue of glabridin that promotes mitochondrial function and is in clinical trials for obesity treatment, on the development of SS in non-obese diabetic NOD/ShiLtJ mice. HGR4113 inhibited IL-17 production by regulating STAT3 activity and the metabolic profile of splenic CD4 + T cells; it also increased the frequency of IL-10-producing regulatory B cells and decreased immunoglobulin production. Oral administration of HGR4113 (100 mg/kg) improved salivary flow rate, reduced lymphocyte infiltration and lowered inflammatory cytokine levels in the salivary glands of NOD/ShiLtJ mice. HGR4113 also decreased the frequencies of splenic IL-17-producing T and B cells, germinal-centre B cells and plasma cells ex vivo in NOD/ShiLtJ mice. Additionally, 3D epithelial structure formation from salivary gland cells of HGR4113-treated NOD/ShiLtJ mice increased, as did the levels of E-cadherin, aquaporin-5, α-SMA and cytokeratin-14. Finally, treatment with HGR4113 promoted the development of 3D salivary epithelial structures in vitro. HGR4113 improves salivary gland hypofunction by inhibiting lymphocyte infiltration and inflammation in the salivary glands and restoring damaged salivary tissue in SS-like NOD/ShiLtJ mice.

Mitochondrial damage in fibroblast-like synoviocytes (FLSs) is a key factor involved in the development and progression of rheumatoid arthritis (RA). In this study, we investigated the role of mitochondrial dysfunction of FLSs in the pathogenesis of RA. We induced inflammation by stimulating FLSs with TNF and IL17. Then, we transplanted fresh mitochondria into stimulated FLSs and evaluated the mitochondrial and lysosomal functions, macroautophagic/autophagic activity, and the STING1-associated cell death pathway. Next, we transplanted mitochondria or gold nanoparticle-conjugated mitochondria (GNP-Mito) into collagen-induced arthritis (CIA) mice and evaluated their therapeutic effects in vivo. Mitochondrial and lysosomal activities were decreased and autophagosomes accumulated in the stimulated FLSs. Furthermore, the STING1 signaling pathway and STING1-associated cell death were increased in the inflammatory condition. Mitochondrial transplantation into stimulated FLSs enhanced the mitochondrial and lysosomal activities and activated the autophagic activity, as demonstrated by decreased numbers of autophagosomes and increased numbers of autolysosomes. Mitochondrial transplantation decreased and increased the Th17 and Treg populations, respectively. Mitochondrial function and autophagic activity were enhanced by mitochondrial transplantation. Taken together, our results demonstrate that mitochondrial dysfunction in FLSs plays a pivotal role in the pathophysiology of RA and mitochondrial transplantation has therapeutic potential for RA development and progression.Abbreviations: ATP:adenosine triphosphate; CGAS: cyclic GMP-AMP synthase; CIA:collagen-induced arthritis; FLS: fibroblast-like synoviocytes; GNP:gold nanoparticle; ROS: reactive oxygen species; SQSTM1/p62:sequestosome 1; STING1: stimulator of interferon response cGAMPinteractor 1; MAP1LC3B/LC3B: microtubule associated protein 1 lightchain 3 beta.

Current biomarkers, including serum C-reactive protein (CRP) and fecal calprotectin, have limitations in monitoring disease activity of ulcerative colitis (UC). Regenerating islet-derived protein 3α (REG3α), which is constitutively produced by Paneth cells, is a bactericidal C-type protein against Gram-positive bacteria. Preliminary studies suggest that REG3α may serve as a promising novel blood-based biomarker for assessing disease activity in patients with UC. A total of 128 patients with UC were prospectively enrolled. Blood samples were obtained on the same day as endoscopy. Serological markers including REG3α, CRP, albumin, and serum calprotectin were measured. The clinical and endoscopic activity were assessed using the total Mayo score (remission, mild, or moderate-to-severe) and the Mayo endoscopic subscore (MES), respectively. Serum levels of REG3α, CRP, albumin, and calprotectin were significantly correlated with clinical activity (Mayo score ≥ 6) (Spearman's ρ = 0.362, P < 0.001; ρ = 0.429, P < 0.001; ρ = -0.312, P < 0.001; and ρ = 0.253, P = 0.004, respectively). Serum levels of REG3α, CRP, and albumin were also significantly correlated with endoscopic activity (MES ≥ 2) (ρ = 0.362, P < 0.001; ρ = 0.420, P < 0.001; and ρ = -0.240, P = 0.006, respectively), whereas serum calprotectin was not (ρ = 0.147, P = 0.098). The combination of serum REG3α and CRP predicted clinical and endoscopic activity with AUC values of 0.847 and 0.783, respectively, showing improved discriminatory performance compared with the individual biomarkers in this cohort. Among 19 patients who underwent serial follow-up of REG3α levels, a significant decrease was observed during periods of clinical improvement (P = 0.005), although this finding should be interpreted as preliminary. REG3α is a promising blood-based biomarker associated with both clinical and endoscopic activity in UC. When interpreted together with CRP, it showed improved discriminatory performance in this cohort. This serum-based approach may be useful as an adjunctive option when stool-based testing is less feasible. However, the combined REG3α-CRP model should be considered exploratory, and the serial monitoring findings should be interpreted as preliminary. Further validation in larger, independent cohorts, including direct comparison with fecal calprotectin, is required before broader clinical application can be considered.

Background Osteoarthritis (OA), a chronic degenerative disorder, induces pain, joint inflammation, and destruction of the articular cartilage matrix. Curcumin and omega-3 have been used as dietary supplements for OA due to their anti-inflammatory and antioxidant properties. However, there is no evidence demonstrating a synergistic effect in OA. The current study aimed to investigate the therapeutic effects and underlying mechanism of a combination of curcumin and omega-3 in the treatment of OA. Methods Wistar rats were injected with monosodium iodoacetate to induce OA. Oral treatments of a vehicle, curcumin, curcumin and omega 3, or celecoxib were administered. Pain was analyzed according to the paw withdrawal latency, paw withdrawal threshold, and weight bearing ability. The joint was isolated from OA rats, and cartilage damage was evaluated using histomorphological techniques, the Mankin scoring system, and micro computed tomography analysis. Protein expression in the joint was examined using immunohistochemistry. The expression levels of catabolic markers were measured in curcumin and omega-3-treated OA chondrocytes. Results The OA animal model revealed diminished pain and cartilage conservation in response to the combined treatment. mRNA levels of matrix metalloproteinase 1 (MMP1), MMP3, and MMP13 were reduced in interleukin-1 beta-simulated human OA chondrocytes. Additionally, mitochondrial markers, cytochrome c oxidase 4, and TOMM20, were increased by the combination treatment. Conclusions These findings suggest promising therapeutic outcomes for the combined treatment of curcumin and omega-3 in OA patients.

Sjögren’s syndrome (SS) is a chronic autoimmune disease in which inflammatory cells infiltrate the exocrine glands, reducing glandular secretory function and ultimately resulting in keratoconjunctivitis sicca (dry eyes) and xerostomia (oral dryness). Cardiovascular risk factors are more prevalent in patients with SS than in healthy controls; patients with SS and metabolic syndrome also have higher leptin and inflammatory cytokine levels. In this study, we investigated the effects of HGR4113, a structural analog of glabridin that promotes mitochondrial function and is in clinical trials for obesity treatment, on the development of Sjögren’s syndrome in non-obese diabetic NOD/ShiLtJ (NOD) mice. HGR4113 inhibited IL-17 production by regulating STAT3 activity and the metabolic profile of splenic CD4 + T cells; it also increased the frequency of IL-10-producing regulatory B cells and decreased immunoglobulin production. Oral administration of HGR4113 (100 mg/kg) improved salivary flow rate, reduced lymphocyte infiltration, and lowered inflammatory cytokine levels in the salivary glands of NOD mice. HGR4113 also decreased the frequencies of splenic IL-17-producing T and B cells, germinal center B cells, and plasma cells ex vivo in NOD mice. Additionally, organoid formation from salivary gland stem cells of HGR4113-treated NOD mice increased, as did the levels of E-cadherin-14, aquaporin-5, α-SMA, and cytokeratin-14. Finally, treatment with HGR4113 promoted salivary gland organoid formation in vitro . HGR4113 improves salivary gland hypofunction by inhibiting lymphocyte infiltration and inflammation in the salivary glands and restoring damaged salivary tissue in SS-like NOD mice.

For patients with ankylosing spondylitis (AS) who experience inefficacy or adverse events with biologics, no recommendations exist regarding the preference for class cycling or switching as a second- or higher-line biologics. Previous studies on the drug retention of TNF and IL-17 inhibitors in AS patients with prior biologics exposure have limitations, including relatively short follow-up periods, exclusion of patients with extra-articular manifestations, and a primary focus on second-line treatment. This study aimed to compare the retention rates of TNF and IL-17 inhibitors in AS patients with prior biologics experience, over a relatively longer follow-up period in real clinical practice. A total of 148 AS cases receiving either a TNF or IL-17 inhibitor as a second- or higher-line biologic were retrospectively analyzed after propensity score matching. Patient characteristics at the time of cycling or switching and drug retention were compared between the two groups. Subgroup analyses were conducted based on the reasons for drug discontinuation. Cox regression analyses were used to identify the factors associated with drug discontinuation. The median follow-up period was 31.4 months, and drug survival tended to be lower for IL-17 inhibitors than for TNF inhibitors in the Kaplan–Meier analysis (P = 0.134). The lower retention of IL-17 inhibitors was more pronounced when discontinuations unrelated to treatment failure were censored (P = 0.034) or when used for reasons other than psoriasis aggravation (P = 0.028). However, in multivariable Cox regression, the number of previous biologics (HR: 1.62, 95

Sjogren’s disease (SjD) is a systemic autoimmune disease primarily affecting the exocrine glands. Systemic manifestations, including hepatic involvement, are increasingly recognized. This study aimed to delineate the clinical features and associated factors of autoimmune hepatic involvement in SjD. A retrospective analysis was conducted on patients diagnosed with SjD at Seoul St. Mary’s Hospital over the past 10 years. Autoimmune hepatic involvement was defined by fulfilling diagnostic criteria for autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC). Clinical, serological, and demographic data were obtained from medical records. Among 1119 patients with SjD, 51 (4.6%) had autoimmune hepatic involvement. AIH (64.7%) was the most common type, followed by PBC (27.5%) and overlapping disease (7.8%). Compared to those without hepatic involvement, affected patients were older at diagnosis (p = 0.003) and showed higher frequencies of thrombocytopenia, splenomegaly, anti-centromere antibody (ACA), and elevated antinuclear antibody titers as measured by indirect immunofluorescence (IFI-HEp-2) (all p < 0.001). Multivariable analysis identified splenomegaly, elevated IFI-HEp-2 titer, and ACA positivity as independent factors associated with hepatic involvement. Most patients responded well to immunosuppressive therapy, with only a small proportion (15.7%) progressing to liver fibrosis. Autoimmune hepatic involvement is relatively uncommon but clinically meaningful in patients with SjD.

BackgroundChildhood onset systemic lupus erythematosus (cSLE) exhibits more severe and more aggressive clinical features compared to adult onset SLE. We investigated factors associated with long-term outcomes among the initial parameters at the time of diagnosis in cSLE.Patients and methodsThis study included patients initially diagnosed with cSLE who were less than 18 years old between January 2009 and December 2021. We excluded patients with prior diagnoses, those transferred from another hospitals, individuals with clinical findings related to infection or post-transplantation, and underlying diseases. A retrospective review of electronic medical records was conducted to gather initial laboratory data, and assess clinical manifestations, including SLE disease activity index-2K (SLDAI-2k). We analyzed parameters associated with survival, as well as events such as flare, complications, and new organ involvement.ResultsA total of 109 patients were enrolled in this study. The mean age was 14.4 ± 2.3 years old, and the female to male ratio was 7.4:1. Twenty-eight patients (25.7%) were diagnosed during the pre-pubertal period. The overall survival rate was 92.9 % (median: 5.0 years). The causes of death were intractable macrophage activation syndrome (n = 2), disease related state (n = 2), and infection (n = 2). The factors related to survival were elevated C-reactive protein (CRP, p = .017, HR: 2.396, 95% CI: 1.165 ∼4.926) in multi-variate analysis, although there were association with CRP, SLEDAI-2K, and false positivity for syphilis (p < .05) in univariate analysis. The event free survival was 10.4% and was related to SLEDAI-2K, anti-Smith antibody, and false positivity for syphilis (p < .05) in univariate analysis. In multivariate analysis, factors associated with event were SLEDAI-2K (p = .035, HR: 2.82, 95% CI: 1.078∼7.375) and, anti-Smith antibody (p = .019, HR: 3.262, 95% CI: 1.218∼8.741).ConclusionInitial SLEDAI-2K and bio-markers for immune response were related to survival and events during follow-up. Clinicians should focus on initial disease activity and laboratory parameters when predicting long-term outcomes in cSLE.

Background: Salivary gland ultrasonography (SGUS) is widely used in primary Sjögren's syndrome (pSS). Many studies have investigated its diagnostic usefulness concerning replacing invasive minor salivary gland biopsy (MSGB), however, the broader clinical value remains unclear. Objectives: In this study, we aimed to assess the clinical significance of SGUS in evaluating secretory function, disease activity, and lymphoma risk factors in pSS. Methods: 150 pSS patients who visited Seoul St. Mary's Hospital between January 2019 and July 2023 were included. All subjects were evaluated with SGUS, MGSB, and secretory function tests. Salivary gland function-related parameters, systemic disease activity-related parameters, and laboratory data related to lymphoma risk factors were retrospectively obtained. The association between SGUS grades and parameters related to secretory function or systemic disease activity was determined. Subgroup analyses based on SGUS grade or the presence of lymphadenopathy (LAP) in SGUS were also performed. Results: SGUS grades were significantly correlated with all other parameters related to salivary gland secretory function. Specifically, they were significantly associated with overall ESSDAI scores, scores of ESSDAI glandular domain, scores of ESSPRI dryness domain, and VAS, respectively. Notably, patients with highest SGUS grade (overall score = 6) showed higher prevalence of laboratory risk factors or extraglandular manifestations potentially related to lymphoma development, compared to the others. Patients having LAP detected by SGUS exhibited lower salivary flow rates, and higher scores in ESSDAI, ESSPRI, and VAS. Conclusion: Our results suggest that SGUS grades and the presence of LAP in SGUS findings are associated with clinical parameters representing secretory function and disease activity in pSS. High SGUS grades are associated with risk factors for lymphoma development. REFERENCES: [1] Esther Mossel et al., Histopathology, salivary flow and ultrasonography of the parotid gland: three complementary measurements in primary Sjögren's syndrome, Rheumatology 2022;61:2472–2482 [2] K. Delli et al., Can salivary gland ultrasonography replace salivary gland biopsy in the diagnosis of Sjögren's syndrome?, Clin Exp Rheumatol 2022; 40: 2443-2449 Acknowledgements: NIL. Disclosure of Interests: None declared.

[This corrects the article DOI: 10.1371/journal.pone.0259130.].

Recent studies have highlighted that the microbiome is the essential factor that can modulate the clinical activity of immunotherapy. However, the role of the microbiome varies significantly across different immunotherapies, suggesting that it is critical to understand the precise function of the microbiome in each type of immunotherapy. While many previous studies primarily focus on summarizing the role of the microbiome in immune checkpoint inhibitors, we seek to explore a novel aspect of the microbiome in other immunotherapies such as mesenchymal stem cell therapy, chimeric antigen receptor T cell therapy, and antibodies-based therapy (e.g., adalimumab, infliximab, bevacizumab, denosumab, etc.) which are rarely summarized in previous reviews. Moreover, we highlight innovative strategies for utilizing microbiome and microbial metabolites to enhance the clinical response of immunotherapy. Collectively, we believe that our manuscript will provide novel insights and innovative approaches to the researchers, which could drive the development of the next generation of personalized therapeutic interventions using microbiomes.

Th17 cells are activated by STAT3 factors in the nucleus, and these factors are correlated with the pathologic progression of rheumatoid arthritis (RA). Recent studies have demonstrated the presence of STAT3 in mitochondria, but its function is unclear. We investigated the novel role of mitochondrial STAT3 (mitoSTAT3) in Th17 cells and fibroblast-like synoviocytes (FLSs) and analyzed the correlation of mitoSTAT3 with RA. We used a collagen-induced arthritis (CIA) mouse model to determine the effect of mitochondrial STAT3. We observed changes in the RA mouse model via the use of a mitochondrial STAT3-inducing vector and inhibitor. We observed the accumulation of abnormal autophagosomes, increased inflammatory cell death signaling, and decreased mitoSTAT3 activity in FLSs from both patients with RA and patients with IL-17-treated FLSs. We first discovered that IL-17 increased the accumulation of abnormal autophagosomes and the expression of inflammatory cell death factors in synovial fibroblasts and decreased mitoSTAT3 activation. In a mouse model of CIA, arthritis and joint inflammation were decreased by injection vectors that induced mitoSTAT3 overexpression. The abnormal accumulation of autophagosomes and the expression of inflammatory cell death factors were also decreased in these mice. In mouse and human immune cells, ZnSO4, an inducer of mitochondrial STAT3, decreases the production of reactive oxygen species, the IL-17 concentration, and differentiation into Th17 cells. However, mitoSTAT3 blockade accelerated the development of arthritis, inflammatory cell death, and abnormal autophagosome/autophagolysosome formation. Therefore, this study suggests a novel inhibitory mechanism of RA using mitoSTAT3 via the regulation of autophagy, Th17 differentiation, and inflammatory cell death. Rheumatoid arthritis is a long-term disease where the immune system attacks the joints, causing pain and swelling. Researchers have found that a protein called mitoSTAT3, located in the mitochondria, might help reduce inflammation in RA. Researchers used mice with arthritis and human cells to study mitoSTAT3’s role. They increased mitoSTAT3 levels in mice and observed less joint damage and inflammation and found that mitoSTAT3 helps control a process called autophagy. This is important because poor autophagy can worsen RA. The results showed that boosting mitoSTAT3 reduced inflammation and joint damage in mice. The researchers concluded that mitoSTAT3 could be a new target for RA treatment by improving cell cleanup processes and reducing harmful immune responses. In the future, therapies that increase mitoSTAT3 might help people with RA by reducing inflammation and joint damage. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Background/Aims Renal relapse has known to be a poor prognostic factor in patients with lupus nephritis (LN), but there were few studies that identified the risk factors of renal relapse in real world. We conducted this study based on 35-years of experience at a single center to find out predictors of renal relapse in Korean patients with LN after achieving complete response (CR). Methods We retrospectively analyzed the clinical, laboratory, pathologic and therapeutic parameters in 296 patients of LN who reached CR. The cumulative risk and the independent risk factors for renal relapse were examined by Kaplan-Meier methods and Cox proportional hazards regression analyses, respectively. Results The median follow-up period from CR was 123 months. Renal relapse had occurred in 157 patients. Renal relapse occurred in 38.2%, 57.6% and 67.9% of patients within 5-, 10-, and 20-year, respectively. The age at diagnosis of SLE and LN were significantly younger, and the proportions of severe proteinuria and serum hypoalbuminemia were higher in patients with renal relapse. Interestingly, the proportion of receiving cytotoxic maintenance treatment was higher in patients with renal relapse. In Cox proportional hazards regression analyses, only young-age onset of LN (by 10 years, HR = 0.779, p = 0.007) was identified to independent predictor of renal relapse. Conclusions Young-age onset of LN was only independent predictor and the patients with severe proteinuria and serum hypoalbuminemia also tended to relapse more, despite of sufficient maintenance treatment. Studies on more effective maintenance treatment regimens and duration are needed to reduce renal relapse.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, abnormal inflammation, and fibrosis of the skin and internal organs, notably the skin and lungs, significantly impairing quality of life. There is currently no cure for SSc, and its etiology remains largely unknown, presenting a primary barrier to effective treatment. We investigated the role of interleukin-21 (IL-21) in the pathogenesis of SSc. Methods: We assessed the expression levels of fibrosis-related genes in human dermal fibroblasts exposed to IL-21 and TGF beta. We also induced SSc in wild-type C57BL/6 mice and IL-21 knockout (KO) mice with a C57BL/6 background using bleomycin (Bleomycin). Histological analyses were conducted on skin and lung tissues from these mice. The distribution and expression levels of fibrosis-related proteins in the tissues were examined via immunohistochemistry and quantitative real-time PCR. Furthermore, we measured the frequency of Th1, Th2, and Th17 cells among splenocytes through flow cytometry. Results: IL-21 activation led to STAT3 phosphorylation more than TGF beta in dermal fibroblasts. In IL-21 KO mice with BLM-induced SSc, skin thickness and lung fibrosis were reduced. The absence of IL-21 in these mice resulted in suppressed expression of fibrosis-related genes, including Col1a1, Col1a2, Col3a1, CTGF, alpha-SMA, STAT3, and TGF beta, in the skin and lungs. It also led to a decreased frequency of Th1, Th2, and Th17 cells, as well as a lower Th17/Treg ratio among splenocytes, factors known to contribute to the development of SSc. Conclusions: IL-21 contributes to the development of SSc by promoting the expression of fibrosis-related genes and modulating the levels of CD4+ T cells.