Arthritis Research & Therapy最新文献

{"title":"Gout-associated SNP at the IL1RN-IL1F10 region is associated with altered cytokine production in PBMCs of patients with gout and controls","authors":"Orsolya I. Gaal, Megan Leask, Valentin Nica, Georgiana Cabău, Medeea Badii, Ioana Hotea, Dennis M de Graaf, Zhenhua Zhang, Yang Li, Cristina Pamfil, Simona Rednic, Tony R. Merriman, Tania O. Crișan, Leo A.B. Joosten","doi":"10.1186/s13075-024-03436-0","DOIUrl":"https://doi.org/10.1186/s13075-024-03436-0","url":null,"abstract":"Gout is caused by the response of the innate immune system to monosodium urate (MSU) crystals. A recent gout GWAS identified a signal of genetic association at a locus encompassing IL1RN-IL1F10. Colocalisation analysis using Genotype Tissue Expression Database (GTEx) eQTL data showed that the signal overlaps with genetic control of IL1RN/IL1F10 gene expression. We assess the functional implications of IL1RN rs9973741, the lead gout-associated variant. We conducted functional validation of IL1RN rs9973741 in patients with gout and controls. The transcription level of IL1RN/IL1F10 was investigated in unstimulated or MSU-crystal co-stimulated PBMCs. Ex vivo functional assays were performed in PBMCs stimulated with C16 + MSU crystals or LPS for 24 h. Cytokine levels were assessed by ELISA. In unstimulated PBMCs, no association of IL1RN rs9973741 (gout risk allele G) to IL1RN expression was observed while IL-1F10 was hindered by low expression at both transcriptional and protein levels. However, G allele carriers showed lower IL1RN expression in PBMCs stimulated with C16/MSU crystal and lower concentrations of circulating IL-1Ra in both controls and gout patients. PBMCs depicted less spontaneous IL-1Ra release in GG homozygous controls and lower IL-1Ra production in response to C16 + MSU crystal costimulation in patients with gout. The G allele was associated with elevated IL-1β cytokine production in response to C16 + MSU crystal stimulation in controls. The gout risk allele G associates with lower circulating IL-1Ra, lower IL-1Ra production in PBMC assays and elevated IL-1β production in PBMCs challenged with C16 + MSU crystals but not in unchallenged cells. Our data indicate that the genetic signal that associates with gout at IL1RN-IL1F10 region functions to alter expression of IL-1Ra when stimulated by MSU crystals.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"170 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaphorin 5A promotes Th17 differentiation via PI3K-Akt-mTOR in systemic lupus erythematosus","authors":"Xin Chen, Lingjiang Zhu, Jieying Xu, Qi Cheng, Yuanji Dong, Yifan Xie, Li Hua, Yan Du","doi":"10.1186/s13075-024-03437-z","DOIUrl":"https://doi.org/10.1186/s13075-024-03437-z","url":null,"abstract":"Previously, we reported that serum Semaphorin 5 A (Sema5A) levels were increased in systemic lupus erythematosus (SLE) patients compared with healthy controls (HC), and elevated Sema5A correlated with disease activity and lupus nephritis in SLE patients. In this study, we aimed to further understand the role of Sema5A in promoting Th17 cells differentiation in SLE. Sema5A, interferon gamma (IFN-γ), interleukin 4 (IL-4), interleukin 17 A (IL-17 A) and interleukin 10 (IL-10) were measured by Enzyme Linked Immunosorbent Assay (ELISA). RNA and protein were isolated from peripheral blood mononuclear cells (PBMCs) in SLE patients and HC. Expression of PlexinA1 and PlexinB3 were measured by quantitative RT-PCR (qRT-PCR) and Western Blot. Th cell subsets were detected by flow cytometry. Treatment with recombinant human Sema5A (rhSema5A) and small interfering RNA (siRNA) were employed to examine the in vitro effect of Sema5A in CD4+T cell differentiation in SLE patients. IL-17 A elevated in SLE patients and positively correlated with Sema5A. PlexinA1 was upregulated and mainly expressed in CD4+ T cells of SLE; Sema5A treatment induced the differentiation of Th17 cells, while did not affect the Th1 and Th2 skewing. These effects were associated with an upregulation of the transcription factor RORγt by Th17 cells, but not T-bet or GATA3 in Th1 and Th2 cells, respectively. Knock down PlexinA1 regulates IL-17 A production by CD4+T cells. Functional assays showed that Sema5A-PlexinA1 axis promoted Th17 cells differentiation via PI3K/Akt/mTOR signaling. These findings demonstrated that Sema5A-PlexinA1 axis acts as a key mediator on Th17 differentiation, suggesting that Sema5A might be a novel therapeutic target in SLE.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"6 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic effects of extracellular vesicles derived from mesenchymal stem cells primed with disease-conditioned-immune cells in systemic lupus erythematosus.","authors":"Eun Wha Choi, Il Seob Shin, I-Rang Lim, Jihye Lee, Bongkum Choi, Sungjoo Kim","doi":"10.1186/s13075-024-03435-1","DOIUrl":"10.1186/s13075-024-03435-1","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is an incurable chronic autoimmune disease of unknown etiology. Therefore, the development of new treatments is urgently needed. This study aimed to investigate the therapeutic effects of extracellular vesicles (EV) derived from immortalized mesenchymal stem cells (iMSCs) primed with conditioned media obtained from disease-conditioned immune cells (CM-EV) and iMSC-derived EV (ASC-EV) in a murine model of SLE.</p><p><strong>Methods: </strong>Female NZB/W F1 mice were divided into the control (C, n = 15), ASC-EV (E, n = 15), and CM-EV (CM, n = 15) groups. Mice in the C, E, and CM groups were intravenously administered saline, ASC-EV, and CM-EV, respectively, once weekly from 6 to 42 weeks of age.</p><p><strong>Results: </strong>Compared to the ASC-EV, the CM-EV showed a significant increase in TGF-β1 production and miR-155-5p and miR-142-3p expression. CM-EV treatment increased survival, decreased anti-dsDNA antibody levels, and ameliorated renal histopathology. Although ASC-EV treatment significantly reduced the incidence of severe proteinuria and improved renal histopathology, it did not significantly improve survival rate. ASC-EV or CM-EV treatment significantly decreased the proportion of pro-inflammatory macrophages (CD11c + CD206-; M1) and M1:M2 ratio. Additionally, CM-EV treatment significantly increased the expression of anti-inflammatory macrophages (CD11c-CD206 + ; M2). Moreover, CM-EV treatment significantly decreased the expression of lupus-specific miRNAs (miR-182-5p and miR-183-5p) in the spleen.</p><p><strong>Conclusions: </strong>EV derived from iMSCs primed with conditioned media obtained from disease-conditioned immune cells exert immunomodulatory effects and ameliorate SLE in a murine model.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":"201"},"PeriodicalIF":4.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automatic knee osteoarthritis severity grading based on X-ray images using a hierarchical classification method.","authors":"Jian Pan, Yuangang Wu, Zhenchao Tang, Kaibo Sun, Mingyang Li, Jiayu Sun, Jiangang Liu, Jie Tian, Bin Shen","doi":"10.1186/s13075-024-03416-4","DOIUrl":"10.1186/s13075-024-03416-4","url":null,"abstract":"<p><strong>Background: </strong>This study aims to develop a hierarchical classification method to automatically assess the severity of knee osteoarthritis (KOA).</p><p><strong>Methods: </strong>This retrospective study recruited 4074 patients. Clinical diagnostic indicators and clinical diagnostic processes were applied to develop a hierarchical classification method that involved four sub-task classifications. These four sub-task classifications were the classification of Kellgren-Lawrence (KL) grade 0-2 and KL grade 3-4, KL grade 3 and KL grade 4, KL grade 0 and KL grade 1-2, and KL grade 1 and KL grade 2, respectively. To extract the features of clinical diagnostic indicators, four U-Net models were first used to segment the total joint space (TJS), the lateral joint space (LJS), the medial joint space (MJS), and osteophytes, respectively. Based on the segmentation result of TJS, the region of knee subchondral bone was generated. Then, geometric features were extracted based on segmentation results of the LJS, MJS, TJS, and osteophytes, while radiomic features were extracted from the knee subchondral bone. Finally, the geometric features, radiomic features, and combination of geometric features and radiomic features were used to construct the geometric model, radiomic model, and combined model in KL grading, respectively. A strict decision strategy was used to evaluate the performance of the hierarchical classification method in all X-ray images of testing cohort.</p><p><strong>Results: </strong>The U-Net models achieved relatively satisfying performances in the segmentation of the TJS, the LJS, the MJS, and the osteophytes with the dice similarity coefficient of 0.88, 0.86, 0.88, and 0.64 respectively. The combined models achieved the best performance in KL grading. The accuracy of combined models was 98.50%, 81.65%, 82.07%, and 74.10% in the classification of KL grade 0-2 and KL grade 3-4, KL grade 3 and KL grade 4, KL grade 0 and KL grade 1-2, and KL grade 1 and KL grade 2, respectively. For all X-ray images of the testing cohort, the accuracy of the hierarchical classification method was 65.98%.</p><p><strong>Conclusion: </strong>The hierarchical classification method developed in the current study is a feasible approach to assess the severity of KOA.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":"203"},"PeriodicalIF":4.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between circulating cell-free mitochondrial DNA content and severity of knee degeneration in patients with knee osteoarthritis: a cross-sectional study.","authors":"Yan-Lin Wu, Shao-Gui Wan, Yi Long, Hua Ye, Jia-Ming Yang, Yun Luo, Yan-Biao Zhong, Li Xiao, Hai-Yan Chen, Mao-Yuan Wang","doi":"10.1186/s13075-024-03438-y","DOIUrl":"10.1186/s13075-024-03438-y","url":null,"abstract":"<p><strong>Background: </strong>Knee osteoarthritis (KOA) is characterized by mitochondrial damage and increased inflammation. Circulating cell-free mitochondrial DNA (ccf-mtDNA), which originates from damaged mitochondria, is an endogenous damage-associated molecular pattern (DAMPs) molecule that may trigger inflammation and is recognized as a potential biomarker for various diseases. In this study, we investigated the potential association between plasma ccf-mtDNA content and its use as a diagnostic biomarker in patients with KOA.</p><p><strong>Methods: </strong>We collected plasma samples from patients with KOA and healthy controls (HC). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect ccf-mtDNA content in the plasma samples. We used the Kellgren-Lawrence (K-L) classification criteria to classify patients with KOA into four grades: I-IV. Disease severity in patients with KOA was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Next, Spearman analysis was performed to observe the correlation between ccf-mtDNA content and the K-L classification and WOMAC score. Logistic regression analysis was used to evaluate the relationship between ccf-mtDNA and KOA risk.</p><p><strong>Results: </strong>In total, we enrolled 60 patients with KOA and HC who were matched for age, sex, and body mass index (BMI). We found that plasma ccf-mtDNA contents were significantly higher in patients with KOA (median, 2.44; quartile range, 1.10-3.79) than in HC (median, 1.08; quartile range, 0.52-2.12) (P < 0.0001). Plasma ccf-mtDNA content sequentially increased following the KOA class I-IV group (P = 0.040) and positively correlated with the K-L classification (r = 0.369, P = 0.004) and WOMAC scores (r = 0.343, P = 0.007). The ccf-mtDNA content did not significantly differ between patients with bilateral and those with single KOA (P = 0.083). Patients with high levels of ccf-mtDNA had a significantly increased risk of KOA compared with those with low levels of ccf-mtDNA (odds ratio [OR], 4.15, 95% confidence interval [CI], 1.71-10.07; P = 0.002). Quartile analysis revealed a significant dose-dependent association (P trend < 0.001).</p><p><strong>Conclusion: </strong>Our study's findings showed that plasma ccf-mtDNA was highly expressed in patients with KOA compared with HC. Furthermore, ccf-mtDNA content is significantly associated with the severity and risk of KOA. Therefore, its detection may provide insight into the prevention and treatment of KOA.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":"202"},"PeriodicalIF":4.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis refractory to biologic therapy: 2-year clinical and radiographic results from the open-label extension of the SELECT-AXIS 2 study","authors":"Xenofon Baraliakos, Désirée van der Heijde, Joachim Sieper, Robert Davies Inman, Hideto Kameda, Walter Peter Maksymowych, Ivan Lagunes-Galindo, Xianwei Bu, Peter Wung, Koji Kato, Anna Shmagel, Atul Deodhar","doi":"10.1186/s13075-024-03412-8","DOIUrl":"https://doi.org/10.1186/s13075-024-03412-8","url":null,"abstract":"The efficacy and safety of upadacitinib in patients with ankylosing spondylitis (AS) and inadequate response/intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR) were evaluated through 1 year in the SELECT-AXIS 2 study. Here, we assess 2-year efficacy, safety, and imaging outcomes in SELECT-AXIS 2. Patients who received continuous upadacitinib, and those who switched from placebo to upadacitinib at week 14, could enter the open-label extension (OLE). Efficacy endpoints included Assessment of SpondyloArthritis international Society (ASAS) and Axial Spondyloarthritis Disease Activity Score (ASDAS) responses, and changes from baseline in measures of disease activity, back pain, function, and quality of life. Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). As observed (AO) and AO with non-responder imputation (AO-NRI) analyses were used for binary endpoints; AO with mixed-effects model for repeated measures (AO-MMRM) for continuous endpoints; and AO-analysis of covariance for mSASSS. Treatment-emergent adverse events (TEAEs) in patients receiving ≥ 1 upadacitinib dose through week 104 are presented as events (E)/100 patient-years (PY). Subgroup analyses were performed by prior tumor necrosis factor/interleukin-17 inhibitor exposure and bDMARD lack of efficacy/intolerance. Of 420 patients who entered the bDMARD-IR AS study, 409 entered the OLE, and 331 (continuous upadacitinib, n = 163; placebo to upadacitinib, n = 168) completed week 104. Improvements in efficacy measures were sustained through the OLE, with similar response rates between the continuous upadacitinib and placebo to upadacitinib groups at week 104. At week 104, 64.9% and 61.7% of patients, respectively, had achieved ASAS 40% response (AO-NRI). Mean changes from baseline were similar between the two groups at week 104 across measures (ASDAS: -2.1 and -2.0; total back pain: -4.9 and -4.6, respectively; AO-MMRM). Over 93.0% of patients showed no radiographic progression (mSASSS mean change from baseline < 2) at week 104. The overall TEAE rate was 165.2 E/100 PY, with low rates of major adverse cardiovascular and venous thromboembolic events (0.3 E/100 PY each). Upadacitinib efficacy, including very low rates of radiographic progression, was demonstrated through 104 weeks in treatment-refractory patients with active AS. Treatment was well tolerated, with no newly identified safety signals. NCT04169373.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"95 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small heterodimer partner-interacting leucine zipper protein suppresses pain and cartilage destruction in an osteoarthritis model by modulating the AMPK/STAT3 signaling pathway","authors":"Jeonghyeon Moon, Keun-Hyung Cho, JooYeon Jhun, JeongWon Choi, Hyun-Sik Na, Jeong Su Lee, Seung Yoon Lee, Jun-Ki Min, Anan Shetty, Sung-Hwan Park, Seok Jung Kim, Mi-La Cho","doi":"10.1186/s13075-024-03417-3","DOIUrl":"https://doi.org/10.1186/s13075-024-03417-3","url":null,"abstract":"Osteoarthritis (OA) is a degenerative joint disease caused by the breakdown of joint cartilage and adjacent bone. Joint injury, being overweight, differences in leg length, high levels of joint stress, abnormal joint or limb development, and inherited factors have been implicated in the etiology of OA. In addition to physical damage to the joint, a role for inflammatory processes has been identified as well. Small heterodimer partner-interacting leucine zipper protein (SMILE) regulates transcription and many cellular functions. Among the proteins activated by SMILE is the peroxisome proliferator-activated receptor (PPAR) γ, which mediates the activities of CD4 + T helper cells, including Th1, Th2, and Th17, as well as Treg cells. PPAR-γ binds to STAT3 to inhibit its transcription, thereby suppressing the expression of the NF-κB pathway, and in turn, the expression of the inflammatory cytokines interferon (IFN), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, which are sub-signals of STAT3 and NF-κB. OA was induced in control C57BL/6 mice and in C57BL/6-derived SMILE-overexpressing transgenic (SMILE Tg) mice. The protein expression levels in the joint and spleen tissues were analyzed by immunohistochemistry and immunofluorescence images. In addition, flow cytometry was performed for detecting changes of the changes of immune cells. Less cartilage damage and significantly reduced levels of OA biomarkers (MMP13, TIMP3 and MCP-1) were observed in SMILE Tg mice. Immunohistochemistry performed to identify the signaling pathway involved in the link between SMILE expression and OA revealed decreased levels of IL-1β, IL-6, TNF-α, and phosphorylated AMPK in synovial tissues as well as a significant decrease in phosphorylated STAT3 in both cartilage and synovium. Changes in systemic immune cells were investigated via flow cytometry to analyze splenocytes isolated from control and SMILE Tg mice. SMILE Tg mice had elevated proportions of CD4 + IL-4 + cells (Th2) and CD4 + CD25 + Foxp3 + cells (Treg) and a notable decrease in CD4 + IL-17 + cells (Th17). Our results show that overexpressed SMILE attenuates the symptoms of OA, by increasing AMPK signaling and decreasing STAT3, thus reducing the levels of inflammatory immune cells.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"36 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross-sectional study from lupus registry of nationwide institutions (LUNA)","authors":"Takahisa Onishi, Ken-ei Sada, Keigo Hayashi, Yoshia Miyawaki, Ryusuke Yoshimi, Yasuhiro Shimojima, Shigeru Ohno, Hiroshi Kajiyama, Kunihiro Ichinose, Shuzo Sato, Michio Fujiwara, Nobuyuki Yajima, Takashi Kida, Yusuke Matsuo, Keisuke Nishimura, Takashi Yamane","doi":"10.1186/s13075-024-03434-2","DOIUrl":"https://doi.org/10.1186/s13075-024-03434-2","url":null,"abstract":"Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis. This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage. Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 ≤ PSL < 7.5 mg, 5.2 for 7.5 ≤ PSL < 10 mg, 9.0 for 10 ≤ PSL < 20 mg, and 43.1 for PSL ≥ 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis. This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"10 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of GPM6B as a novel therapeutic target in Osteoarthritis","authors":"Chongyang Feng, Lin Liu, Jinxue Zhang, Linxiao Wang, Ke Lv, Hongbo Li, Yong Ding","doi":"10.1186/s13075-024-03430-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03430-6","url":null,"abstract":"Osteoarthritis (OA) is the most common motor system disease in older people, characterized by a high incidence and significant social and economic burden. Women have a higher risk of OA, more severe clinical symptoms, and a higher rate of disabilities than men. However, the pathogenesis of OA remains unclear. Therefore, we screened for differentially expressed genes (DEGs) in OA patients of different sex and searched for new targets that may be involved in regulating the development of OA. The study compared the expression of DEGs in synovial fluid exosomes between male and female patients with OA through RNA sequencing combined with bioinformatics analysis using public data. To evaluate the screened DEGs, synovial tissue and fluid samples were obtained from patients with OA who underwent joint replacement surgery. SiRNA-mediated knockdown in vitro experiments were performed to investigate the role of glycoprotein membrane 6B (GPM6B). Meanwhile, GPM6B gene knockout mice were used to assess the in vivo pathological roles of GPM6B in OA. The results revealed that GPM6B is a potential target associated with OA. Immunofluorescence staining demonstrated that GPM6B was expressed in fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes in patients with OA. In vitro experiments confirmed that GPM6B knockdown can reduce the expression of inflammatory factors in primary FLS from patients with OA. Under inflammatory conditions, GPM6B knockdown can reduce the expression of matrix metalloproteinases as well as proliferation of FLS. In addition, using a destabilization of the medial meniscus-induced OA model, we revealed that GPM6B is associated with OA progression in mice. Thus, we provided evidence that GPM6B act as a new target associated with OA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"41 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil and mononuclear leukocyte pathways and upstream regulators revealed by serum proteomics of adult and juvenile dermatomyositis","authors":"A. Clare Sparling, James M. Ward, Kakali Sarkar, Adam Schiffenbauer, Payam Noroozi Farhadi, Michael A. Smith, Saifur Rahman, Kamelia Zerrouki, Frederick W. Miller, Jian-Liang Li, Kerry A. Casey, Lisa G. Rider","doi":"10.1186/s13075-024-03421-7","DOIUrl":"https://doi.org/10.1186/s13075-024-03421-7","url":null,"abstract":"Serum protein abundance was assessed in adult and juvenile dermatomyositis (DM and JDM) patients to determine differentially regulated proteins, altered pathways, and candidate disease activity biomarkers. Serum protein expression from 17 active adult DM and JDM patients each was compared to matched, healthy control subjects by a multiplex immunoassay. Pathway analysis and protein clustering of the differentially regulated proteins were examined to assess underlying mechanisms. Candidate disease activity biomarkers were identified by correlating protein expression with disease activity measures. Seventy-eight of 172 proteins were differentially expressed in the sera of DM and JDM patients compared to healthy controls. Forty-eight proteins were differentially expressed in DM, 32 proteins in JDM, and 14 proteins in both DM and JDM. Twelve additional differentially expressed proteins were identified after combining the DM and JDM cohorts. C-X-C motif chemokine ligand 10 (CXCL10) was the most strongly upregulated protein in both DM and JDM sera. Other highly upregulated proteins in DM included S100 calcium binding protein A12 (S100A12), CXCL9, and nicotinamide phosphoribosyltransferase (NAMPT), while highly upregulated proteins in JDM included matrix metallopeptidase 3 (MMP3), growth differentiation factor 15 (GDF15), and von Willebrand factor (vWF). Pathway analysis indicated that phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), and toll-like receptor 7 (TLR7) signaling were activated in DM and JDM. Additional pathways specific to DM or JDM were identified. A protein cluster associated with neutrophils and mononuclear leukocytes and a cluster of interferon-associated proteins were observed in both DM and JDM. Twenty-two proteins in DM and 24 proteins in JDM sera correlated with global, muscle, and/or skin disease activity. Seven proteins correlated with disease activity measures in both DM and JDM sera. IL-1 receptor like 1 (IL1RL1) emerged as a candidate global disease activity biomarker in DM and JDM. Coordinate analysis of protein expression in DM and JDM patient sera by a multiplex immunoassay validated previous gene expression studies and identified novel dysregulated proteins, altered signaling pathways, and candidate disease activity biomarkers. These findings may further inform the assessment of DM and JDM patients and aid in the identification of potential therapeutic targets.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"215 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}