Taejun Yoon, Jang Woo Ha, Jung Yoon Pyo, Eunhee Ko, Sung Soo Ahn, Jason Jungsik Song, Yong-Beom Park, Sang-Won Lee
{"title":"Serum syndecan1 has the potential to reflect activity at diagnosis and predict death during follow-up in patients with ANCA-associated vasculitis","authors":"Taejun Yoon, Jang Woo Ha, Jung Yoon Pyo, Eunhee Ko, Sung Soo Ahn, Jason Jungsik Song, Yong-Beom Park, Sang-Won Lee","doi":"10.1186/s13075-024-03393-8","DOIUrl":"https://doi.org/10.1186/s13075-024-03393-8","url":null,"abstract":"This study investigated whether serum syndecan1 at diagnosis reflects activity at diagnosis and predicts poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The study included 79 patients with AAV from the cohort of Korean patients diagnosed with AAV. AAV-specific indices, including the Birmingham vasculitis activity score (BVAS), five-factor score (FFS), 36-item short-form survey (SF-36) physical and mental component summary (PCS and MCS), and vasculitis damage index (VDI), were assessed. Laboratory data including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also collected. The highest tertile and upper half of the BVAS were tentatively defined as having high AAV activity. Serum syndecan1 levels were measured in sera stored at diagnosis. Serum syndecan1 at diagnosis was significantly correlated with AAV activity and functional status, as assessed by BVAS, FFS, SF-36 PCS, MCS, and acute-phase reactants, including ESR and CRP. Patients with serum syndecan1 ≥ 76.1 ng/mL at diagnosis, and those with serum syndecan1 ≥ 60.0 ng/mL at diagnosis showed significantly higher risks for the highest tertile and the upper half of BVAS at diagnosis than those without, respectively. Patients with serum syndecan1 ≥ 120.1 ng/mL at diagnosis had a significantly higher risk for all-cause mortality during follow-up than those without, and further, exhibited a significantly lower cumulative patients’ survival rate than those without. Serum syndecan1 at diagnosis may not only reflect AAV activity at diagnosis but may also be associated with all-cause mortality during follow-up.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":"166"},"PeriodicalIF":4.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276045","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}
Yukai Wang, Shaoqi Chen, Shaoyu Zheng, Zexuan Zhou, Weijin Zhang, Guangzhou Du, Angelina Mikish, Barbara Ruaro, Cosimo Bruni, Anna-Maria Hoffmann-Vold, Luna Gargani, Marco Matucci-Cerinic, Daniel E Furst
{"title":"A versatile role for lung ultrasound in systemic autoimmune rheumatic diseases related pulmonary involvement: a narrative review","authors":"Yukai Wang, Shaoqi Chen, Shaoyu Zheng, Zexuan Zhou, Weijin Zhang, Guangzhou Du, Angelina Mikish, Barbara Ruaro, Cosimo Bruni, Anna-Maria Hoffmann-Vold, Luna Gargani, Marco Matucci-Cerinic, Daniel E Furst","doi":"10.1186/s13075-024-03399-2","DOIUrl":"https://doi.org/10.1186/s13075-024-03399-2","url":null,"abstract":"Systemic autoimmune rheumatic diseases (SARDs) related pulmonary disease is highly prevalent, with variable clinical presentation and behavior, and thus is associated with poor outcomes and negatively impacts quality of life. Chest high resolution computed tomography (HRCT) is still considered a fundamental imaging tool in the screening, diagnosis, and follow-up of pulmonary disease in patients with SARDs. However, radiation exposure, economic burden, as well as lack of point-of-care CT equipment limits its application in some clinical situation. Ultrasound has found a place in numerous aspects of the rheumatic diseases, including the vasculature, skin, muscle, joints, kidneys and in screening for malignancies. Likewise it has found increasing use in the lungs. In the past two decades, lung ultrasound has started to be used for pulmonary parenchymal diseases such as pneumonia, pulmonary edema, lung fibrosis, pneumothorax, and pleural lesions, although the lung parenchymal was once considered off-limits to ultrasound. Lung ultrasound B-lines and irregularities of the pleural line are now regarded two important sonographic artefacts related to diffuse parenchymal lung disease and they could reflect the lesion extent and severity. However, its role in the management of SARDs related pulmonary involvement has not been fully investigated. This review article will focus on the potential applications of lung ultrasound in different pulmonary scenarios related with SARDs, such as interstitial lung disease, diffuse alveolar hemorrhage, diaphragmatic involvement, and pulmonary infection, in order to explore its value in clinical daily practice.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"7 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236433","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}
Damiano Currado, Francesca Saracino, Piero Ruscitti, Annalisa Marino, Ilenia Pantano, Marta Vomero, Onorina Berardicurti, Viktoriya Pavlych, Claudio Di Vico, Francesco Caso, Luisa Costa, Marco Tasso, Federica Camarda, Francesca Misceo, Francesco De Vincenzo, Addolorata Corrado, Luisa Arcarese, Amelia Rigon, Marta Vadacca, Erika Corberi, Lyubomyra Kun, Francesca Trunfio, Andrea Pilato, Ludovica Lamberti, Francesco Paolo Cantatore, Federico Perosa, Giuliana Guggino, Raffaele Scarpa, Paola Cipriani, Francesco Ciccia, Roberto Giacomelli, Luca Navarini
{"title":"Pain catastrophizing negatively impacts drug retention rate in patients with Psoriatic Arthritis and axial Spondyloarthritis: results from a 2-years perspective multicenter GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica) study","authors":"Damiano Currado, Francesca Saracino, Piero Ruscitti, Annalisa Marino, Ilenia Pantano, Marta Vomero, Onorina Berardicurti, Viktoriya Pavlych, Claudio Di Vico, Francesco Caso, Luisa Costa, Marco Tasso, Federica Camarda, Francesca Misceo, Francesco De Vincenzo, Addolorata Corrado, Luisa Arcarese, Amelia Rigon, Marta Vadacca, Erika Corberi, Lyubomyra Kun, Francesca Trunfio, Andrea Pilato, Ludovica Lamberti, Francesco Paolo Cantatore, Federico Perosa, Giuliana Guggino, Raffaele Scarpa, Paola Cipriani, Francesco Ciccia, Roberto Giacomelli, Luca Navarini","doi":"10.1186/s13075-024-03396-5","DOIUrl":"https://doi.org/10.1186/s13075-024-03396-5","url":null,"abstract":"Chronic pain and inflammation are common features of rheumatic conditions such as Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA), often needing prolonged medication treatment for effective management. Maintaining drug retention is essential for both achieving disease control and improving patients' quality of life. This study investigates the influence of pain catastrophizing, a psychological response to pain, on the drug retention rates of PsA and axSpA patients. A two-year prospective multicenter observational study involved 135 PsA and 71 axSpA patients. Pain Catastrophizing Scale (PCS) was employed to assess pain catastrophizing. Univariable and multivariable regression analyses were utilized to identify factors associated with drug retention. In the PsA group, patients early discontinuing therapy showed higher baseline disease activity as well as higher incidence of comorbid fibromyalgia. Notably, pain catastrophizing, specifically the domains of Helplessness, Magnification, and Rumination, were significantly elevated in PsA patients who interrupted the treatment. Multivariable analysis confirmed pain catastrophizing as an independent predictor of drug suspension within two years. In axSpA, drug discontinuation was associated with female gender, shorter disease duration, higher baseline disease activity as well as elevated levels of pain catastrophizing. Univariable analysis supported the role of pain catastrophizing, including its domains, as predictors of treatment interruption. However, limited events in axSpA patients precluded a multivariate analysis. This prospective study emphasizes the impact of pain catastrophizing on drug retention in patients with PsA and axSpA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"3 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236430","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":"Use of belimumab in treating patients with systemic lupus erythematosus: a single-center, real-world retrospective study","authors":"Zhaohui Su, Chunyi Zhang, Congcong Gao, Chaoying Li, Ruxv Li, Zhaohui Zheng","doi":"10.1186/s13075-024-03389-4","DOIUrl":"https://doi.org/10.1186/s13075-024-03389-4","url":null,"abstract":"To investigate the efficacy and safety of belimumab in the treatment of systemic lupus erythematosus (SLE) in a real-world setting and provide a valuable reference for clinical treatment. In this retrospective study, 101 patients with SLE who came to our hospital from March 2020 to September 2022, 56 of whom with lupus nephritis (LN), were selected. All patients received belimumab in combination with standard of care(SoC)therapy regimen for more than 52 weeks and their clinical/laboratory data, assessment of disease activity, glucocorticoids dosage and occurrence of adverse events were recorded. Lupus Low Disease Activity State (LLDAS) and DORIS remission as a primary goal in the treatment of SLE. The groups were classified according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K): SLEDAI-2 K < 6 was categorized as the mild group (mild activity) and SLEDAI-2 K ≥ 6 was categorized as the active group (moderate-severe activity). The disease of the two groups mentioned above were assessed using the SELENA-SLEDAI Flare Index (SFI) and the SLE Responder Index-4 (SRI-4), respectively. Furthermore, we used complete remission (CR) and partial remission (PR) in the kidney as the standard for efficacy evaluation for LN patients. After 52 weeks of treatment with belimumab, patients’ complement levels increased significantly (p < 0.05); Other indicators such as 24-hour urine protein quantification and daily glucocorticoids dose decreased compared to pretreatment (p < 0.05). At 52 weeks, (i) after evaluation, the whole group of patients showed significant improvement in their condition; (ii) 55.4% of patients achieved LLDAS and 23.8% achieved DORIS remission; (iii) 73.2% of patients with LN achieved CR, 16.1% achieved PR. Adverse reactions were observed in 15 patients (14.9%), all of which normalized after symptomatic treatment. In general, during treatment with belimumab, immunological and biochemical indices improved in SLE patients, urinary protein levels were reduced in LN patients, and the rate of renal function remission was effectively increased; At the same time, the use of belimumab is associated with a low frequency of side effects, good overall tolerability and a favorable safety profile.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"10 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236429","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":"Truth unveiled by time and the marbled definition of D2T-RA: retrospective analysis on the persistence of the difficult-to-treat status among refractory RA patients","authors":"Gilberto Cincinelli, Gabriella Maioli, Cristina Posio, Ennio Giulio Favalli, Francesca Ingegnoli, Roberto Caporali","doi":"10.1186/s13075-024-03390-x","DOIUrl":"https://doi.org/10.1186/s13075-024-03390-x","url":null,"abstract":"The current EULAR definition of difficult-to-treat rheumatoid arthritis (D2T-RA) identifies patients with active disease refractory to multiple treatments at a single time point, without considering the persistence of this condition over time. The study aimed to assess difficult-to-treat rheumatoid arthritis (D2T-RA) over 12 months, considering persistence over time rather than a single time point, in a real-life cohort. In a single-center real-life cohort, demographic and clinic data were cross-sectionally collected for each patient at baseline and retrospectively over the previous 12 months bimonthly. For each timepoint, the prevalence of D2T-RA patients was calculated, and patients meeting the EULAR definition for at least 6 months were defined as persistent D2T-RA (pD2T-RA). Finally, the clinical characteristics associated with the time-based definition of pD2T-RA were analyzed. Among 610 adult RA patients, 104 were refractory to ≥ 2 treatments. Initially, 41.3% met D2T-RA criteria, but only 27.9% fulfilled persistent D2T-RA (pD2T-RA) criteria over 6 months. The pD2T-RA group was associated with male gender, higher HAQ and Charlson Comorbidity Index scores, more failed treatments, and use of non-NSAID analgesics. Logistic regression linked pD2T-RA to higher SDAI and CRP values, and the use of glucocorticoids or analgesics. Chronic use of glucocorticoids was strongly associated with pD2T-RA. The application of a temporal criterion allowed for the selection of a subgroup of pD2T-RA patients who differ from those who meet the definition of D2T-RA only episodically. Chronic use of glucocorticoids was the factor most strongly associated with pD2T-RA status. What is already known about this subject? Since the institution of the D2T-RA definition, many efforts have been made to characterize this subpopulation's prevalence as well as clinical and demographical features. However, no studies have so far faced the temporal maintenance of the D2T-RA status. What does this study add? A definition of persistent or episodic D2T-RA is proposed according to the temporal trajectory of D2T-RA status, resulting in approximately 27% of D2T-RA patients persistently fulfilling the pD2T-RA definition. At each single time point, one-third of D2T-RA patients are represented by episodic D2T-RA patients. How might this impact on clinical practice? Persistent D2T-RA definition may serve to further homogenize the D2T-RA population.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"329 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235254","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}
Daniel P. Joyce, Jeffrey S. Berger, Allison Guttmann, Ghadeer Hasan, Jill P. Buyon, H. Michael Belmont, Jane Salmon, Anca Askanase, Joan Bathon, Laura Geraldino-Pardilla, Yousaf Ali, Ellen M. Ginzler, Chaim Putterman, Caroline Gordon, Charles G. Helmick, Kamil E. Barbour, Heather T. Gold, Hilary Parton, Peter M. Izmirly
{"title":"Prevalence of cardiovascular events in a population-based registry of patients with systemic lupus erythematosus","authors":"Daniel P. Joyce, Jeffrey S. Berger, Allison Guttmann, Ghadeer Hasan, Jill P. Buyon, H. Michael Belmont, Jane Salmon, Anca Askanase, Joan Bathon, Laura Geraldino-Pardilla, Yousaf Ali, Ellen M. Ginzler, Chaim Putterman, Caroline Gordon, Charles G. Helmick, Kamil E. Barbour, Heather T. Gold, Hilary Parton, Peter M. Izmirly","doi":"10.1186/s13075-024-03395-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03395-6","url":null,"abstract":"The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of patients with systemic lupus erythematosus (SLE), was used to investigate the prevalence of cardiovascular disease events (CVE) and compare rates among sex, age and race/ethnicity to population-based controls. Patients with prevalent SLE in 2007 aged ≥ 20 years in the MLSP were included. CVE required documentation of a myocardial infarction or cerebrovascular accident. We calculated crude risk ratios and adjusted risk ratios (ARR) controlling for sex, age group, race and ethnicity, and years since diagnosis. Data from the 2009–2010 National Health and Nutrition Examination Survey (NHANES) and the 2013–2014 NYC Health and Nutrition Examination Survey (NYC HANES) were used to calculate expected CVE prevalence by multiplying NHANES and NYC HANES estimates by strata-specific counts of patients with SLE. Crude prevalence ratios (PRs) using national and NYC estimates and age standardized prevalence ratios (ASPRs) using national estimates were calculated. CVE occurred in 13.9% of 1,285 MLSP patients with SLE, and risk was increased among men (ARR:1.7, 95%CI:1.2–2.5) and older adults (age > 60 ARR:2.5, 95%CI:1.7–3.8). Compared with non-Hispanic Asian patients, CVE risk was elevated among Hispanic/Latino (ARR:3.1, 95%CI:1.4-7.0) and non-Hispanic Black (ARR:3.5, 95%CI1.6-7.9) patients as well as those identified as non-Hispanic and in another or multiple racial groups (ARR:4.2, 95%CI:1.1–15.8). Overall, CVE prevalence was higher among patients with SLE than nationally (ASPR:3.1, 95%CI:3.0-3.1) but did not differ by sex. Compared with national race and ethnicity-stratified estimates, CVE among patients with SLE was highest among Hispanics/Latinos (ASPR:4.3, 95%CI:4.2–4.4). CVE was also elevated among SLE registry patients compared with all NYC residents. Comparisons with age-stratified national estimates revealed PRs of 6.4 (95%CI:6.2–6.5) among patients aged 20–49 years and 2.2 (95%CI:2.1–2.2) among those ≥ 50 years. Male (11.3, 95%CI:10.5–12.1), Hispanic/Latino (10.9, 95%CI:10.5–11.4) and non-Hispanic Black (6.2, 95%CI:6.0-6.4) SLE patients aged 20–49 had the highest CVE prevalence ratios. These population-based estimates of CVE in a diverse registry of patients with SLE revealed increased rates among younger male, Hispanic/Latino and non-Hispanic Black patients. These findings reinforce the need to appropriately screen for CVD among all SLE patients but particularly among these high-risk patients.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"12 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231457","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}
Hongxia Yang, Chao Sun, Lifang Ye, Yuetong Xu, Sang Lin, Qinglin Peng, Guochun Wang, Xin Lu
{"title":"Association of anti-HMGCR antibodies of the IgM isotype with refractory immune-mediated necrotizing myopathy","authors":"Hongxia Yang, Chao Sun, Lifang Ye, Yuetong Xu, Sang Lin, Qinglin Peng, Guochun Wang, Xin Lu","doi":"10.1186/s13075-024-03387-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03387-6","url":null,"abstract":"Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician’s Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (β = 3.830; p < 0.0001), muscle VAS (β = 2.893; p < 0.0001), MMT8 (β=-19.368; p < 0.0001), and creatine kinase (CK) levels (β = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (β = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis. • Anti-HMGCR IgM-positive patients had a younger age of onset and more neck weakness than anti-HMGCR IgM-negative patients. • The levels of anti-HMGCR IgG and IgM are associated with disease activity in anti-HMGCR-positive patients. • Anti-HMGCR IgM is associated with refractory outcome and poor prognosis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"383 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166285","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":"Activation of circulating TFH17 cells associated with activated naive and double negative 2 B cell expansion, and disease activity in systemic lupus erythematosus patients","authors":"Tipanan Khunsri, Pongsakorn Thawornpan, Pachara Tianpothong, Thanitta Suangtamai, Pintip Ngamjanyaporn, Chaniya Leepiyasakulchai, Kittikorn Wangriatisak, Prapaporn Pisitkun, Patchanee Chootong","doi":"10.1186/s13075-024-03394-7","DOIUrl":"https://doi.org/10.1186/s13075-024-03394-7","url":null,"abstract":"Systemic lupus erythematosus (SLE) is the quintessential autoimmune disease, as it is characterized by hyperactivity of CD4+ T cells and subsequently drives lupus pathology. Follicular helper T (TFH) cells play an important role in B cell maturation and antibody production. However, which specific subset of cTFH cells drives B cell function and contributes to the development of anti-dsDNA antibodies and SLE pathogenesis remains unclear. Peripheral blood mononuclear cells from SLE patients with inactive (n = 11) and active (n = 21) were used to determine and detect frequencies and phenotypes of circulating TFH cells (cTFH), memory cTFH, and B cell subsets. The correlations among cTFH cell subsets and phenotypes, B cell subsets, anti-dsDNA autoantibodies, and clinical parameters were analyzed. In subjects with active SLE, cTFH1 and cTFH17 cells were significantly expanded and activated. These expanded cTFH cells expressed memory phenotypes; cTFH1 cells were predominantly central memory (CM) type, while cTFH17 cells were largely effector memory (EM) type. Phenotyping B cell subsets in these patients showed increased frequencies of aNAV and DN2 B cells. Clinically, ICOS+ cTFH1, ICOS+ cTFH17 cells, and SLEDAI-2k scores were found to be correlated. Analysis of cTFH-B cell relationship revealed positive correlations among ICOS+ cTFH1 cells, aNAV B cells, and anti-dsDNA antibodies. Activation of ICOS+ cTFH17 cells was significantly related to the expansion of aNAV and DN2 B cells. The presence of CM cells in cTFH1 and cTFH17 subsets was correlated with aNAV and DN2 B cell frequencies. SLE cTFH cells were found to be polarized toward cTFH1 and cTFH17 cells; activation of these cTFH subsets was significantly associated with disease activity score, aNAV, DN2 B cell expansion, and anti-dsDNA antibody level. Thus, the interactions among cTFH1, cTFH17, and B cells likely contribute to the development of autoantibodies and the pathogenesis in SLE.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166283","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":"A phase 3, randomized, double-blind, active-controlled clinical trial to compare BAT1806/BIIB800, a tocilizumab biosimilar, with tocilizumab reference product in participants with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate: treatment period 2 analysis (week 24 to week 48)","authors":"Xiaomei Leng, Piotr Leszczyński, Slawomir Jeka, Shengyun Liu, Huaxiang Liu, Malgorzata Miakisz, Jieruo Gu, Lali Kilasonia, Mykola Stanislavchuk, Xiaolei Yang, Yinbo Zhou, Qingfeng Dong, Marian Mitroiu, Janet Addison, Mourad F. Rezk, Xiaofeng Zeng","doi":"10.1186/s13075-024-03375-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03375-w","url":null,"abstract":"Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24–48). In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated. Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported. In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups. NCT03830203 and EudraCT 2018-002202-31.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"40 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144343","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":"Factors related to elevated serum immunoglobulin G4 (IgG4) levels in a Japanese general population","authors":"Shunsuke Tsuge, Hiroshi Fujii, Mami Tamai, Hiromasa Tsujiguchi, Misaki Yoshida, Nobuhiro Suzuki, Yoshinori Takahashi, Akari Takeji, Shigeto Horita, Yuhei Fujisawa, Takahiro Matsunaga, Takeshi Zoshima, Ryo Nishioka, Hiromi Nuka, Satoshi Hara, Yukiko Tani, Yasunori Suzuki, Kiyoaki Ito, Kazunori Yamada, Satoshi Nakazaki, Akinori Hara, Atsushi Kawakami, Hiroyuki Nakamura, Ichiro Mizushima, Yasunori Iwata, Mitsuhiro Kawano","doi":"10.1186/s13075-024-03391-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03391-w","url":null,"abstract":"Elevated serum immunoglobulin G4 (IgG4) concentrations are one of the characteristic findings in IgG4-related disease (IgG4-RD). This study investigated the frequency of elevated serum IgG4 levels and associated factors in a general Japanese population. Serum IgG4 concentrations were measured in 1,201 residents of Ishikawa prefecture who underwent general medical examinations. Factors associated with elevated serum IgG4 concentrations were assessed by logistic regression analysis. Participants with elevated serum IgG4 were subjected to secondary examinations. The mean serum IgG4 concentration was 44 mg/dL, with 42 (3.5%) participants having elevated serum IgG4 levels. Age- and sex-adjusted logistic regression analyses showed that male sex, older age, and lower intake of lipids and polyunsaturated fatty acids and higher intake of carbohydrates in daily diet were associated with elevated serum IgG4 concentration. Subgroup analyses in men showed that older age, lower estimated glomerular filtration rates based on serum cystatin C (eGFR-cysC) levels, and higher hemoglobin A1c (HbA1c) levels were associated with elevated serum IgG4 concentration. Analyses in women showed that lower intake of lipids and fatty acids and higher intake of carbohydrates were significantly associated with elevated serum IgG4 concentration. One of the 15 participants who underwent secondary examinations was diagnosed with possible IgG4-related retroperitoneal fibrosis. Elevated serum IgG4 levels in a Japanese general population were significantly associated with older age, male gender, and dietary intake of nutrients, with some of these factors identical to the epidemiological features of IgG4-RD.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142432","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}