Pub Date : 2024-03-22DOI: 10.1186/s42358-024-00362-2
Rafael Alves Cordeiro, Nilton Salles Rosa Neto, Henrique Ayres Mayrink Giardini
Gaucher and Fabry diseases are lysosomal storage disorders in which deficient enzyme activity leads to pathological accumulation of sphingolipids. These diseases have a broad phenotypic presentation. Musculoskeletal symptoms and pain complaints are frequently reported by patients. Thus, rheumatologists can be contacted by these patients, contributing to the correct diagnosis, earlier indication of appropriate treatment and improvement of their prognosis. This review describes important concepts about Gaucher and Fabry diseases that rheumatologists should understand to improve patients' quality of life and change the natural history of these diseases.
{"title":"What should rheumatologists know about Gaucher disease and Fabry disease? Connecting the dots for an overview.","authors":"Rafael Alves Cordeiro, Nilton Salles Rosa Neto, Henrique Ayres Mayrink Giardini","doi":"10.1186/s42358-024-00362-2","DOIUrl":"10.1186/s42358-024-00362-2","url":null,"abstract":"<p><p>Gaucher and Fabry diseases are lysosomal storage disorders in which deficient enzyme activity leads to pathological accumulation of sphingolipids. These diseases have a broad phenotypic presentation. Musculoskeletal symptoms and pain complaints are frequently reported by patients. Thus, rheumatologists can be contacted by these patients, contributing to the correct diagnosis, earlier indication of appropriate treatment and improvement of their prognosis. This review describes important concepts about Gaucher and Fabry diseases that rheumatologists should understand to improve patients' quality of life and change the natural history of these diseases.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Psoriatic arthritis (PA) is a chronic inflammatory systemic arthritis that can result in loss of functional capacity and joint deformation. This systematic review assessed the effectiveness and safety of biological and target synthetic drugs for treating PA.
Methods: We searched for randomized clinical trials (RCTs) that evaluated the use of Adalimumab, Etanercept, Infliximab, Golimumab, Secukinumab, Certolizumab Pegol and Tofacitinib in the main general databases and clinical trial registers databases. The primary outcomes were ACR 50, PsARC, and serious adverse events. Two independent reviewers performed study selection and data extraction. Network meta-analyses were conducted using a random effects model and frequentist approach. The CINeMA software was used to assess the certainty of evidence.
Results: We included 33 RCTs (n = 11,034). The results from the network meta-analysis for the ACR 50 at 6-months follow-up showed that all drugs were superior to placebo, with Secukinumab (high certainty of evidence), Infliximab (very low certainty of evidence) and Adalimumab (high certainty of evidence) ranking the highest. Regarding the PsARC (at 6-months follow-up), all drugs, except for Golimumab (very low certainty of evidence), were superior to placebo, with Etanercept (low certainty of evidence), Infliximab (low certainty of evidence) and Certolizumab Pegol (low certainty of evidence) being the most effective drugs. There were no significant differences in the risk of serious adverse events between the drugs and placebo. Golimumab (very low certainty of evidence), Secukinumab (low certainty of evidence), and Adalimumab (very low certainty of evidence) ranked the highest for safety.
Conclusions: In conclusion, based on the balance between efficacy and safety, Secukinumab and Adalimumab may be the preferred options among the evaluated drugs for treating patients with PsA. However, caution is necessary when interpreting the safety findings, as they are supported by evidence of low to very low certainty. Consequently, the balance between benefits and potential risks may change as new safety evaluation studies become available.
{"title":"Effectiveness and safety of biological and target synthetic drugs treatment for psoriatic arthritis: a systematic review with network meta-analysis.","authors":"Thais Montezuma, Livia Fernandes Probst, Matheus Oliveira Almeida","doi":"10.1186/s42358-024-00361-3","DOIUrl":"10.1186/s42358-024-00361-3","url":null,"abstract":"<p><strong>Background: </strong>Psoriatic arthritis (PA) is a chronic inflammatory systemic arthritis that can result in loss of functional capacity and joint deformation. This systematic review assessed the effectiveness and safety of biological and target synthetic drugs for treating PA.</p><p><strong>Methods: </strong>We searched for randomized clinical trials (RCTs) that evaluated the use of Adalimumab, Etanercept, Infliximab, Golimumab, Secukinumab, Certolizumab Pegol and Tofacitinib in the main general databases and clinical trial registers databases. The primary outcomes were ACR 50, PsARC, and serious adverse events. Two independent reviewers performed study selection and data extraction. Network meta-analyses were conducted using a random effects model and frequentist approach. The CINeMA software was used to assess the certainty of evidence.</p><p><strong>Results: </strong>We included 33 RCTs (n = 11,034). The results from the network meta-analysis for the ACR 50 at 6-months follow-up showed that all drugs were superior to placebo, with Secukinumab (high certainty of evidence), Infliximab (very low certainty of evidence) and Adalimumab (high certainty of evidence) ranking the highest. Regarding the PsARC (at 6-months follow-up), all drugs, except for Golimumab (very low certainty of evidence), were superior to placebo, with Etanercept (low certainty of evidence), Infliximab (low certainty of evidence) and Certolizumab Pegol (low certainty of evidence) being the most effective drugs. There were no significant differences in the risk of serious adverse events between the drugs and placebo. Golimumab (very low certainty of evidence), Secukinumab (low certainty of evidence), and Adalimumab (very low certainty of evidence) ranked the highest for safety.</p><p><strong>Conclusions: </strong>In conclusion, based on the balance between efficacy and safety, Secukinumab and Adalimumab may be the preferred options among the evaluated drugs for treating patients with PsA. However, caution is necessary when interpreting the safety findings, as they are supported by evidence of low to very low certainty. Consequently, the balance between benefits and potential risks may change as new safety evaluation studies become available.</p><p><strong>Protocol registration: </strong>PROSPERO: CRD42022315577.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-15DOI: 10.1186/s42358-024-00357-z
Nakwon Kwak, Jinyoung Moon, Joong-Yub Kim, Jun Won Park, Jae-Joon Yim
Objectives: The impact of rheumatoid arthritis (RA) on nontuberculous mycobacterial pulmonary disease (NTM-PD) has not been well established. In this study, we investigated the clinical course of NTM-PD in patients with RA and the impact of RA on the prognosis of NTM-PD.
Methods: We analyzed patients who developed NTM-PD after being diagnosed with RA from January 2004 to August 2023 at a tertiary referral hospital in South Korea. The patient's baseline characteristics, clinical course, and prognosis were evaluated. An optimal matching analysis was performed to measure the impact of RA on the risk of mortality.
Results: During the study period, 18 patients with RA [median age, 68 years; interquartile range (IQR) 59-73; female, 88.9%] developed NTM-PD. The median interval between RA diagnosis and subsequent NTM-PD development was 14.8 years (IQR, 8.6-19.5). At a median of 30 months (IQR, 27-105) after NTM-PD diagnosis, 10 of 18 (55.6%) patients received anti-mycobacterial treatment for NTM-PD and 5 (50.0%) patients achieved microbiological cure. When matched to patients with NTM-PD but without RA, patients with both RA and NTM-PD had a higher risk of mortality (adjusted hazard ratio, 8.14; 95% confidence interval, 2.43-27.2).
Conclusion: NTM-PD occurring after RA is associated with a higher risk of mortality than NTM-PD in the absence of RA.
目的:类风湿性关节炎(RA)对非结核分枝杆菌肺病(NTM-PD)的影响尚未明确。在这项研究中,我们调查了 RA 患者 NTM-PD 的临床过程以及 RA 对 NTM-PD 预后的影响:我们分析了 2004 年 1 月至 2023 年 8 月期间在韩国一家三级转诊医院确诊为 RA 后发展为 NTM-PD 的患者。对患者的基线特征、临床过程和预后进行了评估。研究人员进行了最佳匹配分析,以衡量 RA 对死亡风险的影响:研究期间,18 名 RA 患者[中位年龄 68 岁;四分位数间距(IQR)59-73;女性,88.9%]罹患 NTM-PD。从确诊为 RA 到随后出现 NTM-PD 的中位间隔为 14.8 年(IQR,8.6-19.5)。在NTM-PD确诊后的30个月中位数(IQR,27-105),18名患者中有10名(55.6%)接受了NTM-PD抗霉菌治疗,5名(50.0%)患者实现了微生物治愈。如果与患有NTM-PD但无RA的患者进行比对,同时患有RA和NTM-PD的患者的死亡风险更高(调整后危险比为8.14;95%置信区间为2.43-27.2):结论:与无RA的NTM-PD相比,RA后发生的NTM-PD与更高的死亡风险相关。
{"title":"Clinical course of nontuberculous mycobacterial pulmonary disease in patients with rheumatoid arthritis.","authors":"Nakwon Kwak, Jinyoung Moon, Joong-Yub Kim, Jun Won Park, Jae-Joon Yim","doi":"10.1186/s42358-024-00357-z","DOIUrl":"10.1186/s42358-024-00357-z","url":null,"abstract":"<p><strong>Objectives: </strong>The impact of rheumatoid arthritis (RA) on nontuberculous mycobacterial pulmonary disease (NTM-PD) has not been well established. In this study, we investigated the clinical course of NTM-PD in patients with RA and the impact of RA on the prognosis of NTM-PD.</p><p><strong>Methods: </strong>We analyzed patients who developed NTM-PD after being diagnosed with RA from January 2004 to August 2023 at a tertiary referral hospital in South Korea. The patient's baseline characteristics, clinical course, and prognosis were evaluated. An optimal matching analysis was performed to measure the impact of RA on the risk of mortality.</p><p><strong>Results: </strong>During the study period, 18 patients with RA [median age, 68 years; interquartile range (IQR) 59-73; female, 88.9%] developed NTM-PD. The median interval between RA diagnosis and subsequent NTM-PD development was 14.8 years (IQR, 8.6-19.5). At a median of 30 months (IQR, 27-105) after NTM-PD diagnosis, 10 of 18 (55.6%) patients received anti-mycobacterial treatment for NTM-PD and 5 (50.0%) patients achieved microbiological cure. When matched to patients with NTM-PD but without RA, patients with both RA and NTM-PD had a higher risk of mortality (adjusted hazard ratio, 8.14; 95% confidence interval, 2.43-27.2).</p><p><strong>Conclusion: </strong>NTM-PD occurring after RA is associated with a higher risk of mortality than NTM-PD in the absence of RA.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-06DOI: 10.1186/s42358-024-00355-1
Yu-Jing Zhang, Li-Feng Chen, Xu Li, Jian-Hua Chen, Zhang-Kui Tan
Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which might trigger cartilage, bone damage, and disability. Recent studies have suggested that Tetramethylpyrazine (TMP), an alkaloid monomer isolated from the rhizome of the traditional herbal medicine Ligusticum wallichii Franch, exerts a broad spectrum of pharmacological properties, containing anti-inflammatory. This study aimed to analyze the role and underlying mechanism of TMP in RA.
Methods: Under Hypoxia condition, RA-Fibroblast-like synoviocyte (FLS) were treated with TMP at different doses. Cell viability, proliferation, cell cycle progression, and migration were detected using Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry assay, wound healing assay, and transwell assay. Cyclin D1, Proliferating cell nuclear antigen (PCNA), Matrix metalloproteinase-2 (MMP2), MMP9, and hypoxia-inducible factor-1α (HIF-1α) protein levels were measured using western blot assay. Interleukin-6 (IL-6) and IL-8 were evaluated using ELISA. Circular RNA (circRNA) hsa_circ_0005178 (circCDC42BPB), CDC42BPB, and HIF-1α expression were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Binding between HIF-1α and CDC42BPB promoter was predicted by JASPAR and verified using dual-luciferase reporter and Chromatin immunoprecipitation (ChIP) assays.
Results: TMP might hinder FLS proliferation, cycle progression, migration, and inflammatory response under hypoxic conditions. CircCDC42BPB expression was increased in RA patients and RA-FLSs treated with hypoxia, while its level was obviously reduced in RA-FLSs treated with hypoxia and TMP. TMP might abolish hypoxia-induced circCDC42BPB expression. Upregulation of circCDC42BPB might partially overturn the repression of TMP on hypoxia-caused RA-FLS damage. TMP might regulate circCDC42BPB level via HIF-1α in RA-FLSs under hypoxic conditions.
Conclusion: TMP might block RA-FLS injury partly via regulating the HIF-1α- circCDC42BPB pathway, providing a promising therapeutic target for RA.
{"title":"Tetramethylpyrazine alleviates hypoxia-induced proliferation, migration, and inflammatory response of fibroblast-like synoviocytes via inhibiting the HIF-1α- circCDC42BPB pathway.","authors":"Yu-Jing Zhang, Li-Feng Chen, Xu Li, Jian-Hua Chen, Zhang-Kui Tan","doi":"10.1186/s42358-024-00355-1","DOIUrl":"10.1186/s42358-024-00355-1","url":null,"abstract":"<p><strong>Objectives: </strong>Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which might trigger cartilage, bone damage, and disability. Recent studies have suggested that Tetramethylpyrazine (TMP), an alkaloid monomer isolated from the rhizome of the traditional herbal medicine Ligusticum wallichii Franch, exerts a broad spectrum of pharmacological properties, containing anti-inflammatory. This study aimed to analyze the role and underlying mechanism of TMP in RA.</p><p><strong>Methods: </strong>Under Hypoxia condition, RA-Fibroblast-like synoviocyte (FLS) were treated with TMP at different doses. Cell viability, proliferation, cell cycle progression, and migration were detected using Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry assay, wound healing assay, and transwell assay. Cyclin D1, Proliferating cell nuclear antigen (PCNA), Matrix metalloproteinase-2 (MMP2), MMP9, and hypoxia-inducible factor-1α (HIF-1α) protein levels were measured using western blot assay. Interleukin-6 (IL-6) and IL-8 were evaluated using ELISA. Circular RNA (circRNA) hsa_circ_0005178 (circCDC42BPB), CDC42BPB, and HIF-1α expression were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Binding between HIF-1α and CDC42BPB promoter was predicted by JASPAR and verified using dual-luciferase reporter and Chromatin immunoprecipitation (ChIP) assays.</p><p><strong>Results: </strong>TMP might hinder FLS proliferation, cycle progression, migration, and inflammatory response under hypoxic conditions. CircCDC42BPB expression was increased in RA patients and RA-FLSs treated with hypoxia, while its level was obviously reduced in RA-FLSs treated with hypoxia and TMP. TMP might abolish hypoxia-induced circCDC42BPB expression. Upregulation of circCDC42BPB might partially overturn the repression of TMP on hypoxia-caused RA-FLS damage. TMP might regulate circCDC42BPB level via HIF-1α in RA-FLSs under hypoxic conditions.</p><p><strong>Conclusion: </strong>TMP might block RA-FLS injury partly via regulating the HIF-1α- circCDC42BPB pathway, providing a promising therapeutic target for RA.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
If a large amount of urate crystals is deposited in a joint cavity for an extended period of time, bone erosion will occur and gradually cause skeletal muscle necrosis and joint deformity. The aim of this study was to describe the clinical characteristics and factors associated with bone erosion in gout patients with tophi. A total of 210 gout patients with tophi were enrolled and divided into a bone erosion group (n = 135) and a non-bone erosion group (n = 75). Digital radiography (DR) was performed to detect bone erosion in the elbow, wrist, knee, ankle joints, interphalangeal and metatarsophalangeal joints. The clinical characteristics were recorded and compared between the two groups. Multivariate logistic regression analysis was conducted to explore the factors associated with bone erosion. Compared with the non-bone erosion group, the bone erosion group had an older age, longer disease duration of gout and tophi, higher level of serum creatinine (sCr), higher proportion of drinking history and ulceration, and a lower glomerular filtration rate (GFR). Univariate logistic regression analysis results showed that sex, age, body mass index (BMI), gout duration, tophi duration, GFR, white blood cell (WBC) count, sCr level, smoking history, drinking history, and presence of ulceration were associated with bone destruction. Multivariable logistic regression analysis results indicated that tophi duration, drinking history, ulceration and sCr were positively and independently related to bone erosion. Tophi patients with bone erosion presented different clinical characteristics. Tophi duration, drinking history, ulceration and sCr were associated with bone erosion in gout patients with tophi.
{"title":"Clinical characteristics and risk factors associated with bone erosion in patients with tophi","authors":"Zhuyi Ji, Yukai Huang, Ling Liang, Paifeng Lin, Xin Guo, Qidang Huang, Zhengping Huang, Shuyang Chen, Zhixiang Huang, Biao Wang, Lixin Huang, Shanmiao Sun, Weiming Deng, Tianwang Li","doi":"10.1186/s42358-023-00336-w","DOIUrl":"https://doi.org/10.1186/s42358-023-00336-w","url":null,"abstract":"If a large amount of urate crystals is deposited in a joint cavity for an extended period of time, bone erosion will occur and gradually cause skeletal muscle necrosis and joint deformity. The aim of this study was to describe the clinical characteristics and factors associated with bone erosion in gout patients with tophi. A total of 210 gout patients with tophi were enrolled and divided into a bone erosion group (n = 135) and a non-bone erosion group (n = 75). Digital radiography (DR) was performed to detect bone erosion in the elbow, wrist, knee, ankle joints, interphalangeal and metatarsophalangeal joints. The clinical characteristics were recorded and compared between the two groups. Multivariate logistic regression analysis was conducted to explore the factors associated with bone erosion. Compared with the non-bone erosion group, the bone erosion group had an older age, longer disease duration of gout and tophi, higher level of serum creatinine (sCr), higher proportion of drinking history and ulceration, and a lower glomerular filtration rate (GFR). Univariate logistic regression analysis results showed that sex, age, body mass index (BMI), gout duration, tophi duration, GFR, white blood cell (WBC) count, sCr level, smoking history, drinking history, and presence of ulceration were associated with bone destruction. Multivariable logistic regression analysis results indicated that tophi duration, drinking history, ulceration and sCr were positively and independently related to bone erosion. Tophi patients with bone erosion presented different clinical characteristics. Tophi duration, drinking history, ulceration and sCr were associated with bone erosion in gout patients with tophi.","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140026102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-04DOI: 10.1186/s42358-024-00360-4
Huimin Yang, Chao Sun, Xin Wang, Tao Wang, Changhao Xie, Zhijun Li
The labial salivary glands (LSGs) are important for the diagnosis, evaluation of therapeutic efficacy, and genetic analyses of primary Sjögren’s syndrome (pSS). In autoimmune diseases, the recognition of self nucleic acids and viral RNA and DNA through endogenous Toll-like receptor(TLR) triggers the production of type I IFN and pro-inflammatory cytokines, leading to the occurrence and progression of the disease. Here, we detected the expression of TLR7 in LSGs and analyse its correlation with clinical features and serum cytokines in pSS patients. LSGs and serum samples were obtained from 56 pSS patients and 19 non-SS patients (non-pSS patients). The expression of TLR7 in the LSGs was evaluated with immunohistochemistry. The serum levels of interferon-α (IFN-α) and interleukin-6 (IL-6) were quantified by ELISA. Laboratory parameters were measured by clinical standard laboratory techniques. TLR7-positive cells in pSS were localized in the ductal epithelial cells and lymphocytes of LSGs. The expression of TLR7 was upregulated in pSS patients compared with controls. Patients with anti-Ro52 antibody positivity showed higher TLR7 levels than those who were negative but not those with anti-Ro60 and anti-SSB. TLR7 levels were positively associated with the levels of IgG, IgA, ANA, IL-6, IFN-α and serum globulin but were not associated with IgM, C3, C4, or rheumatoid factor (RF) in serum. TLR7 may be involved in the inflammatory response and the production of antibodies in pSS and plays an important role in local and systemic pSS manifestations. This research showed that TLR7 is involved in pSS pathogenesis.
{"title":"Elevated expression of Toll-like receptor 7 and its correlation with clinical features in patients with primary Sjögren’s syndrome","authors":"Huimin Yang, Chao Sun, Xin Wang, Tao Wang, Changhao Xie, Zhijun Li","doi":"10.1186/s42358-024-00360-4","DOIUrl":"https://doi.org/10.1186/s42358-024-00360-4","url":null,"abstract":"The labial salivary glands (LSGs) are important for the diagnosis, evaluation of therapeutic efficacy, and genetic analyses of primary Sjögren’s syndrome (pSS). In autoimmune diseases, the recognition of self nucleic acids and viral RNA and DNA through endogenous Toll-like receptor(TLR) triggers the production of type I IFN and pro-inflammatory cytokines, leading to the occurrence and progression of the disease. Here, we detected the expression of TLR7 in LSGs and analyse its correlation with clinical features and serum cytokines in pSS patients. LSGs and serum samples were obtained from 56 pSS patients and 19 non-SS patients (non-pSS patients). The expression of TLR7 in the LSGs was evaluated with immunohistochemistry. The serum levels of interferon-α (IFN-α) and interleukin-6 (IL-6) were quantified by ELISA. Laboratory parameters were measured by clinical standard laboratory techniques. TLR7-positive cells in pSS were localized in the ductal epithelial cells and lymphocytes of LSGs. The expression of TLR7 was upregulated in pSS patients compared with controls. Patients with anti-Ro52 antibody positivity showed higher TLR7 levels than those who were negative but not those with anti-Ro60 and anti-SSB. TLR7 levels were positively associated with the levels of IgG, IgA, ANA, IL-6, IFN-α and serum globulin but were not associated with IgM, C3, C4, or rheumatoid factor (RF) in serum. TLR7 may be involved in the inflammatory response and the production of antibodies in pSS and plays an important role in local and systemic pSS manifestations. This research showed that TLR7 is involved in pSS pathogenesis.","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140026409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite their rarity, Lyme disease and Whipple’s disease are of significant importance in rheumatology, as both can manifest as chronic arthritis, presenting challenges in the differential diagnosis of inflammatory arthropathies. In Lyme disease, arthritis typically emerges as a late manifestation, usually occurring six months after the onset of erythema migrans. The predominant presentation involves mono- or oligoarthritis of large joints, with a chronic or remitting-recurrent course. Even with appropriate antimicrobial treatment, arthritis may persist due to inadequate immunological control triggered by the disease. In contrast, Whipple’s disease may present with a migratory and intermittent seronegative poly- or oligoarthritis of large joints, preceding classic gastrointestinal symptoms by several years. Both disorders, particularly Whipple’s disease, can be misdiagnosed as more common autoimmune rheumatic conditions such as rheumatoid arthritis and spondyloarthritis. Epidemiology is crucial in suspecting and diagnosing Lyme disease, as the condition is transmitted by ticks prevalent in specific areas of the United States, Europe, and Asia. On the contrary, the causative agent of Whipple’s disease is widespread in the environment, yet invasive disease is rare and likely dependent on host genetic factors. In addition to erythema migrans in Lyme disease and gastrointestinal manifestations in Whipple’s disease, neurological and cardiac involvement can further complicate the course of both. This article offers a comprehensive review of the epidemiological, pathophysiological, clinical, and therapeutic aspects of both diseases.
{"title":"Lyme disease and Whipple’s disease: a comprehensive review for the rheumatologist","authors":"Henrique Ayres Mayrink Giardini, Fabricio Souza Neves, Ivanio Alves Pereira, Rafael Alves Cordeiro","doi":"10.1186/s42358-024-00359-x","DOIUrl":"https://doi.org/10.1186/s42358-024-00359-x","url":null,"abstract":"Despite their rarity, Lyme disease and Whipple’s disease are of significant importance in rheumatology, as both can manifest as chronic arthritis, presenting challenges in the differential diagnosis of inflammatory arthropathies. In Lyme disease, arthritis typically emerges as a late manifestation, usually occurring six months after the onset of erythema migrans. The predominant presentation involves mono- or oligoarthritis of large joints, with a chronic or remitting-recurrent course. Even with appropriate antimicrobial treatment, arthritis may persist due to inadequate immunological control triggered by the disease. In contrast, Whipple’s disease may present with a migratory and intermittent seronegative poly- or oligoarthritis of large joints, preceding classic gastrointestinal symptoms by several years. Both disorders, particularly Whipple’s disease, can be misdiagnosed as more common autoimmune rheumatic conditions such as rheumatoid arthritis and spondyloarthritis. Epidemiology is crucial in suspecting and diagnosing Lyme disease, as the condition is transmitted by ticks prevalent in specific areas of the United States, Europe, and Asia. On the contrary, the causative agent of Whipple’s disease is widespread in the environment, yet invasive disease is rare and likely dependent on host genetic factors. In addition to erythema migrans in Lyme disease and gastrointestinal manifestations in Whipple’s disease, neurological and cardiac involvement can further complicate the course of both. This article offers a comprehensive review of the epidemiological, pathophysiological, clinical, and therapeutic aspects of both diseases.","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140026415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To investigate the role of eye signs in predicting poor outcomes in systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH).
Methods: This prospective observational study recruited patients diagnosed with SLE-PAH from Jan. 2021 to Dec. 2021 at the First Affiliated Hospital of Nanchang University; those with other potential causes of PAH were excluded. The evaluation of various parameters, such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), echocardiography, and risk stratification based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines, was conducted at intervals of every 1-3 months, and a 6-month follow-up period was observed. The primary outcome measure considered improvement if there was a decline in the risk stratification grade at the end point and unimproved if there was no decline. Conjunctival microvascular images were observed and recorded.
Results: A total of 29 SLE-PAH patients were enrolled, comprising 12 in the improved group and 17 in the nonimproved group. All SLE-PAH patients showed various manifestations of eye signs, including vessel twisting, dilation, ischaemic areas, haemorrhages, reticulum deformity, and wound spots. The nonimproved group exhibited significantly lower vessel density (VD) and microvascular flow index (MFI) of conjunctival microvascular images than the improved group. Correlation analysis revealed that VD displayed a negative correlation with the WHO-FC (r = -0.413, p = 0.026) and NT-proBNP (r = -0.472, p = 0.010), as well as a positive correlation with the 6MWD (r = 0.561, p = 0.002). Similarly, MFI exhibited a negative correlation with WHO-FC (r = -0.408, p = 0.028) and NT-proBNP (r = -0.472, p = 0.010) and a positive correlation with 6MWD (r = 0.157, p = 0.004). Multivariate logistic regression analysis indicated that VD (OR 10.11, 95% CI 1.95-52.36), MFI (OR 7.85, 95% CI 1.73-35.67), NT-proBNP, and 6MWD were influential factors in predicting the prognostic improvement of SLE-PAH patients. ROC curve analysis demonstrated that VD, MFI, 6MWD, and NT-proBNP (with respective AUC values of 0.83, 0.83, 0.76, and 0.90, respectively) possessed a sensitivity and specificity of 75 and 100%, as well as 83 and 100%, respectively. Regarding prognostic prediction, VD and MFI exhibited higher sensitivity than 6MWD, whereas MFI displayed higher sensitivity and specificity than NT-proBNP.
Conclusion: SLE-PAH can lead to various conjunctival microvascular manifestations in which vascular density and microvascular flow index can be used to assess cardiopulmonary function and predict therapeutic efficacy and prognosis in SLE-PAH patients.
{"title":"Eye signs as a novel risk predictor in pulmonary arterial hypertension associated with systemic lupus erythematosus.","authors":"Jianbin Li, Jiangbiao Xiong, Pengcheng Liu, Yilin Peng, Shuang Cai, Xia Fang, Shujiao Yu, Jun Zhao, Rui Wu","doi":"10.1186/s42358-024-00356-0","DOIUrl":"10.1186/s42358-024-00356-0","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the role of eye signs in predicting poor outcomes in systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH).</p><p><strong>Methods: </strong>This prospective observational study recruited patients diagnosed with SLE-PAH from Jan. 2021 to Dec. 2021 at the First Affiliated Hospital of Nanchang University; those with other potential causes of PAH were excluded. The evaluation of various parameters, such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), echocardiography, and risk stratification based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines, was conducted at intervals of every 1-3 months, and a 6-month follow-up period was observed. The primary outcome measure considered improvement if there was a decline in the risk stratification grade at the end point and unimproved if there was no decline. Conjunctival microvascular images were observed and recorded.</p><p><strong>Results: </strong>A total of 29 SLE-PAH patients were enrolled, comprising 12 in the improved group and 17 in the nonimproved group. All SLE-PAH patients showed various manifestations of eye signs, including vessel twisting, dilation, ischaemic areas, haemorrhages, reticulum deformity, and wound spots. The nonimproved group exhibited significantly lower vessel density (VD) and microvascular flow index (MFI) of conjunctival microvascular images than the improved group. Correlation analysis revealed that VD displayed a negative correlation with the WHO-FC (r = -0.413, p = 0.026) and NT-proBNP (r = -0.472, p = 0.010), as well as a positive correlation with the 6MWD (r = 0.561, p = 0.002). Similarly, MFI exhibited a negative correlation with WHO-FC (r = -0.408, p = 0.028) and NT-proBNP (r = -0.472, p = 0.010) and a positive correlation with 6MWD (r = 0.157, p = 0.004). Multivariate logistic regression analysis indicated that VD (OR 10.11, 95% CI 1.95-52.36), MFI (OR 7.85, 95% CI 1.73-35.67), NT-proBNP, and 6MWD were influential factors in predicting the prognostic improvement of SLE-PAH patients. ROC curve analysis demonstrated that VD, MFI, 6MWD, and NT-proBNP (with respective AUC values of 0.83, 0.83, 0.76, and 0.90, respectively) possessed a sensitivity and specificity of 75 and 100%, as well as 83 and 100%, respectively. Regarding prognostic prediction, VD and MFI exhibited higher sensitivity than 6MWD, whereas MFI displayed higher sensitivity and specificity than NT-proBNP.</p><p><strong>Conclusion: </strong>SLE-PAH can lead to various conjunctival microvascular manifestations in which vascular density and microvascular flow index can be used to assess cardiopulmonary function and predict therapeutic efficacy and prognosis in SLE-PAH patients.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: This study aimed to investigate the causal impact of inflammatory cytokines on Sjogren's Syndrome (SS) and to identify potential biomarkers for SS clinical management using Mendelian Randomization (MR).
Materials and methods: Leveraging GWAS summary data of inflammatory cytokines and SS, we executed the first two-sample MR analysis. Genetic variants from prior GWASs associated with circulating inflammatory cytokines served as instrumental variables (IVs). Data regarding cytokines were analyzed using the Olink Target-96 Inflammation panel, synthesizing data from 14,824 participants. GWAS summary statistics for SS were procured from the UK Biobank, focusing on samples of European ancestry. To discern the causal relationship between inflammatory cytokines and SS, several MR methodologies, including inverse variance weighted (IVW) and MR-Egger regression, were applied.
Results: After rigorous IV quality control, 91 cytokines were incorporated into the MR analysis. The IVW analysis identified 8 cytokines with a positive association to SS: Axin-1 (OR 2.56, 95% CI 1.07-6.10), T-cell surface glycoprotein CD5 (OR 1.81, 95% CI 1.08-3.02), CUDP1 (OR 1.61, 95% CI 1.00-2.58), CXCL10 (OR 1.92, 95% CI 1.25-2.95), IL-4 (OR 2.18, 95% CI 1.22-3.91), IL-7 (OR 2.35, 95% CI 1.27-4.33), MCP-2 (OR 1.27, 95% CI 1.05-1.54), and TNFRSF9 (OR 1.83, 95% CI 1.03-3.24), suggesting their potential in increasing SS risk.
Conclusion: Our study conducted through MR, identified various inflammatory cytokines associated with SS risk, validating some previous research results and offering some new potential biomarkers for SS. However, these findings necessitate further research for validation and exploration of their precise role in the onset and progression of SS.
目的:本研究旨在探讨炎性细胞因子对斯尤金综合征(SS)的因果影响,并利用孟德尔随机化(MR)方法确定斯尤金综合征临床管理的潜在生物标志物:利用炎性细胞因子和SS的GWAS汇总数据,我们首次进行了双样本MR分析。先前的全球基因组研究中与循环炎症细胞因子相关的基因变异作为工具变量(IV)。有关细胞因子的数据使用 Olink Target-96 Inflammation 面板进行分析,综合了来自 14,824 名参与者的数据。SS的GWAS汇总统计数据来自英国生物库,侧重于欧洲血统的样本。为了确定炎性细胞因子与 SS 之间的因果关系,研究人员采用了几种 MR 方法,包括反方差加权(IVW)和 MR-Egger 回归:经过严格的 IV 质量控制,91 种细胞因子被纳入 MR 分析。IVW 分析确定了 8 种与 SS 呈正相关的细胞因子:Axin-1(OR 2.56,95% CI 1.07-6.10)、T 细胞表面糖蛋白 CD5(OR 1.81,95% CI 1.08-3.02)、CUDP1(OR 1.61,95% CI 1.00-2.58)、CXCL10(OR 1.92,95% CI 1.25-2.95)、IL-4(OR 2.18,95% CI 1.22-3.91)、IL-7(OR 2.35,95% CI 1.27-4.33)、MCP-2(OR 1.27,95% CI 1.05-1.54)和 TNFRSF9(OR 1.83,95% CI 1.03-3.24),表明它们可能增加 SS 风险:我们的研究通过磁共振成像发现了与 SS 风险相关的各种炎症细胞因子,验证了之前的一些研究成果,并为 SS 提供了一些新的潜在生物标志物。然而,这些发现还需要进一步研究,以验证和探索它们在 SS 发病和进展中的确切作用。
{"title":"Inflammatory cytokines and their potential role in Sjogren's syndrome risk: insights from a mendelian randomization study.","authors":"Wenbin Shi, Yuli Xu, Anan Zhang, Xiqun Jia, Shuhua Liu, Ziyang Hu","doi":"10.1186/s42358-024-00354-2","DOIUrl":"10.1186/s42358-024-00354-2","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to investigate the causal impact of inflammatory cytokines on Sjogren's Syndrome (SS) and to identify potential biomarkers for SS clinical management using Mendelian Randomization (MR).</p><p><strong>Materials and methods: </strong>Leveraging GWAS summary data of inflammatory cytokines and SS, we executed the first two-sample MR analysis. Genetic variants from prior GWASs associated with circulating inflammatory cytokines served as instrumental variables (IVs). Data regarding cytokines were analyzed using the Olink Target-96 Inflammation panel, synthesizing data from 14,824 participants. GWAS summary statistics for SS were procured from the UK Biobank, focusing on samples of European ancestry. To discern the causal relationship between inflammatory cytokines and SS, several MR methodologies, including inverse variance weighted (IVW) and MR-Egger regression, were applied.</p><p><strong>Results: </strong>After rigorous IV quality control, 91 cytokines were incorporated into the MR analysis. The IVW analysis identified 8 cytokines with a positive association to SS: Axin-1 (OR 2.56, 95% CI 1.07-6.10), T-cell surface glycoprotein CD5 (OR 1.81, 95% CI 1.08-3.02), CUDP1 (OR 1.61, 95% CI 1.00-2.58), CXCL10 (OR 1.92, 95% CI 1.25-2.95), IL-4 (OR 2.18, 95% CI 1.22-3.91), IL-7 (OR 2.35, 95% CI 1.27-4.33), MCP-2 (OR 1.27, 95% CI 1.05-1.54), and TNFRSF9 (OR 1.83, 95% CI 1.03-3.24), suggesting their potential in increasing SS risk.</p><p><strong>Conclusion: </strong>Our study conducted through MR, identified various inflammatory cytokines associated with SS risk, validating some previous research results and offering some new potential biomarkers for SS. However, these findings necessitate further research for validation and exploration of their precise role in the onset and progression of SS.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-06DOI: 10.1186/s42358-024-00353-3
Matheus Zanata Brufatto, Sean Hideo Shirata Lanças, Taciana de Albuquerque Pedrosa Fernandes, Adriana Maluf Elias Sallum, Lucia Maria Arruda Campos, Ana Paula Sakamoto, Maria Teresa Terreri, Flavio Roberto Sztajnbok, Blanca Elena Rios Gomes Bica, Virginia Paes Leme Ferriani, Luciana Martins de Carvalho, Clovis Artur Almeida Silva, Claudia Saad-Magalhaes
Background: Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis.
Method: A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol.
Results: Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma.
Conclusion: Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.
{"title":"Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review.","authors":"Matheus Zanata Brufatto, Sean Hideo Shirata Lanças, Taciana de Albuquerque Pedrosa Fernandes, Adriana Maluf Elias Sallum, Lucia Maria Arruda Campos, Ana Paula Sakamoto, Maria Teresa Terreri, Flavio Roberto Sztajnbok, Blanca Elena Rios Gomes Bica, Virginia Paes Leme Ferriani, Luciana Martins de Carvalho, Clovis Artur Almeida Silva, Claudia Saad-Magalhaes","doi":"10.1186/s42358-024-00353-3","DOIUrl":"10.1186/s42358-024-00353-3","url":null,"abstract":"<p><strong>Background: </strong>Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis.</p><p><strong>Method: </strong>A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol.</p><p><strong>Results: </strong>Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma.</p><p><strong>Conclusion: </strong>Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}