This study investigated poor prognostic factors for the relapse of interstitial lung disease (ILD) in patients with microscopic polyangiitis (MPA) after remission induction therapy. We enrolled patients diagnosed with MPA complicated by ILD according to the Chapel Hill Consensus definition from 2001 to 2023 in multiple institutions in the REVEAL cohort. All patients who were treated with immunosuppressive therapy were followed up, and those who relapsed with ILD were extracted in this study. We explored the risk factors for predicting ILD relapse in patients with MPA-ILD by comparing the demographic, clinical, laboratory, and radiological findings and treatments between the relapsed and non-relapsed groups on admission. Of 243 patients with MPA, 134 (55.1%) with MPA-ILD were enrolled. Among them, 28 (20.9%) relapsed during a mean follow-up of 4.2 years. The initial serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) levels and the prevalence of usual interstitial pneumonia (UIP) pattern were significantly higher in the relapsed group. The biomarkers were also risk factors for relapse in multivariate Cox regression analysis. The best cut-off values of KL-6, SP-D for predicting ILD relapse were 430 U/mL and 89.5 ng/mL, respectively. We created prediction models based on the best cut-off values for KL-6, SP-D, and the presence of the UIP pattern (KSU model). The 10-year relapse rate was significantly different among patients with MPA-ILD stratified by the number of risk factors based on the KSU model. A higher relapse rate was associated with higher all-cause mortality. The initial serum high KL-6 and SP-D levels and the prevalence of the UIP pattern were associated with ILD relapse in patients with MPA-ILD. Our multicentre cohort study indicated that the KSU model, which consists of KL-6 ≥ 430 U/mL, SP-D ≥ 89.5 ng/mL, and the presence of the UIP pattern, is a useful predictor of ILD relapse in patients with MPA after immunosuppressive therapy.
{"title":"Poor prognostic factors for relapse of interstitial lung disease in microscopic polyangiitis: the Japanese multicentre REVEAL cohort study","authors":"Shogo Matsuda, Takuya Kotani, Ayana Okazaki, Daisuke Nishioka, Yuichi Masuda, Mayu Shiomi, Ryu Watanabe, Tomoki Taniguchi, Atsushi Manabe, Keiichiro Kadoba, Tsuneyasu Yoshida, Ryosuke Hiwa, Wataru Yamamoto, Motomu Hashimoto, Tohru Takeuchi","doi":"10.1186/s13075-024-03453-z","DOIUrl":"https://doi.org/10.1186/s13075-024-03453-z","url":null,"abstract":"This study investigated poor prognostic factors for the relapse of interstitial lung disease (ILD) in patients with microscopic polyangiitis (MPA) after remission induction therapy. We enrolled patients diagnosed with MPA complicated by ILD according to the Chapel Hill Consensus definition from 2001 to 2023 in multiple institutions in the REVEAL cohort. All patients who were treated with immunosuppressive therapy were followed up, and those who relapsed with ILD were extracted in this study. We explored the risk factors for predicting ILD relapse in patients with MPA-ILD by comparing the demographic, clinical, laboratory, and radiological findings and treatments between the relapsed and non-relapsed groups on admission. Of 243 patients with MPA, 134 (55.1%) with MPA-ILD were enrolled. Among them, 28 (20.9%) relapsed during a mean follow-up of 4.2 years. The initial serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) levels and the prevalence of usual interstitial pneumonia (UIP) pattern were significantly higher in the relapsed group. The biomarkers were also risk factors for relapse in multivariate Cox regression analysis. The best cut-off values of KL-6, SP-D for predicting ILD relapse were 430 U/mL and 89.5 ng/mL, respectively. We created prediction models based on the best cut-off values for KL-6, SP-D, and the presence of the UIP pattern (KSU model). The 10-year relapse rate was significantly different among patients with MPA-ILD stratified by the number of risk factors based on the KSU model. A higher relapse rate was associated with higher all-cause mortality. The initial serum high KL-6 and SP-D levels and the prevalence of the UIP pattern were associated with ILD relapse in patients with MPA-ILD. Our multicentre cohort study indicated that the KSU model, which consists of KL-6 ≥ 430 U/mL, SP-D ≥ 89.5 ng/mL, and the presence of the UIP pattern, is a useful predictor of ILD relapse in patients with MPA after immunosuppressive therapy.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"24 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849183","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}
Pub Date : 2024-12-19DOI: 10.1186/s13075-024-03447-x
Bo Broens, Esther J. Nossent, Lilian J. Meijboom, Gerben J. C. Zwezerijnen, Julia Spierings, Jeska K. de Vries-Bouwstra, Jacob M. van Laar, Conny J. van der Laken, Alexandre E. Voskuyl
This study aimed to assess the quantitative uptake of 18F-FDG PET-CT in the lungs of patients with early severe diffuse cutaneous systemic sclerosis (SSc) with and without interstitial lung disease (ILD), compared to controls. In patients with SSc-ILD, 18F-FDG uptake was correlated to high-resolution computed tomography (HRCT) and pulmonary function test (PFT) parameters. A prospective, cross-sectional study was conducted, involving 15 patients with SSc-ILD, 5 patients with SSc without ILD, and 7 controls without SSc. 18F-FDG PET-CT scans were performed following standardized protocols, and quantitative analysis of tracer uptake was conducted in predefined lung regions. In addition, HRCT scans were evaluated for ILD-related radiologic abnormalities. Between-group differences were compared with non-parametric tests, while correlations with PFT parameters were analyzed using Spearman correlation coefficients. 18F-FDG uptake was mainly increased in the dorsobasal lung fields of patients with SSc-ILD compared to SSc without ILD and controls (p = 0.03 and p < 0.001, respectively). 18F-FDG uptake was higher in SSc patients with extensive ILD (≥ 20% vs < 20%, p = 0.04) and correlated with lower DLCO% (R = -0.59, p = 0.02). Ground-glass opacities, with or without reticulation, corresponded to increased 18F-FDG uptake. 18F-FDG PET-CT can detect metabolic activity in the lungs of patients with early severe diffuse cutaneous SSc and ILD, correlating with higher ILD extent (≥ 20%) and lower DLCO%. These results suggest the potential utility of 18F-FDG PET-CT in the early detection of ILD (progression) and aiding in risk stratification.
本研究旨在评估伴有或不伴有间质性肺疾病（ILD）的早期严重弥漫性皮肤系统性硬化症（SSc）患者肺部18F-FDG PET-CT的定量摄取，与对照组相比。在SSc-ILD患者中，18F-FDG摄取与高分辨率计算机断层扫描（HRCT）和肺功能测试（PFT）参数相关。进行了一项前瞻性横断面研究，包括15例SSc-ILD患者，5例SSc无ILD患者和7例无SSc对照。按照标准化方案进行18F-FDG PET-CT扫描，并在预定义的肺区域进行示踪剂摄取的定量分析。此外，HRCT扫描评估ild相关放射学异常。用非参数检验比较组间差异，用Spearman相关系数分析与PFT参数的相关性。与无ILD的SSc和对照组相比，SSc-ILD患者肺背基底野的18F-FDG摄取主要增加（p = 0.03和p < 0.001）。SSc合并广泛ILD患者的18F-FDG摄取较高（≥20% vs < 20%, p = 0.04），并与较低的DLCO%相关（R = -0.59, p = 0.02）。毛玻璃混浊，不论有无网状，都与18F-FDG摄取增加有关。18F-FDG PET-CT可检测早期严重弥漫性皮肤SSc和ILD患者肺部代谢活性，与ILD程度高（≥20%）和DLCO%低相关。这些结果表明18F-FDG PET-CT在早期发现ILD（进展）和帮助风险分层方面的潜在效用。
{"title":"Quantitative 18F-FDG PET-CT can assess presence and extent of interstitial lung disease in early severe diffuse cutaneous systemic sclerosis","authors":"Bo Broens, Esther J. Nossent, Lilian J. Meijboom, Gerben J. C. Zwezerijnen, Julia Spierings, Jeska K. de Vries-Bouwstra, Jacob M. van Laar, Conny J. van der Laken, Alexandre E. Voskuyl","doi":"10.1186/s13075-024-03447-x","DOIUrl":"https://doi.org/10.1186/s13075-024-03447-x","url":null,"abstract":"This study aimed to assess the quantitative uptake of 18F-FDG PET-CT in the lungs of patients with early severe diffuse cutaneous systemic sclerosis (SSc) with and without interstitial lung disease (ILD), compared to controls. In patients with SSc-ILD, 18F-FDG uptake was correlated to high-resolution computed tomography (HRCT) and pulmonary function test (PFT) parameters. A prospective, cross-sectional study was conducted, involving 15 patients with SSc-ILD, 5 patients with SSc without ILD, and 7 controls without SSc. 18F-FDG PET-CT scans were performed following standardized protocols, and quantitative analysis of tracer uptake was conducted in predefined lung regions. In addition, HRCT scans were evaluated for ILD-related radiologic abnormalities. Between-group differences were compared with non-parametric tests, while correlations with PFT parameters were analyzed using Spearman correlation coefficients. 18F-FDG uptake was mainly increased in the dorsobasal lung fields of patients with SSc-ILD compared to SSc without ILD and controls (p = 0.03 and p < 0.001, respectively). 18F-FDG uptake was higher in SSc patients with extensive ILD (≥ 20% vs < 20%, p = 0.04) and correlated with lower DLCO% (R = -0.59, p = 0.02). Ground-glass opacities, with or without reticulation, corresponded to increased 18F-FDG uptake. 18F-FDG PET-CT can detect metabolic activity in the lungs of patients with early severe diffuse cutaneous SSc and ILD, correlating with higher ILD extent (≥ 20%) and lower DLCO%. These results suggest the potential utility of 18F-FDG PET-CT in the early detection of ILD (progression) and aiding in risk stratification.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849185","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}
Neutropenia is more common in patients with systemic lupus erythematosus (SLE) and is a major cause of life-threatening infections. The increased apoptosis of neutrophils is likely to be an essential cause of neutropenia in SLE. However, the detailed mechanisms of increased neutrophil apoptosis in SLE remain unknown. This study focused on the role of Krüppel-like factor 2 (KLF2) in the regulation of neutrophil apoptosis and its association with SLE disease activity. The levels of KLF2 in neutrophils from SLE patients and healthy controls (HCs) were detected by RT-PCR and western blot. The relationship between the levels of KLF2 and the apoptosis levels of neutrophils in SLE patients was analyzed. The KLF2 inhibitor Geranylgeranyl pyrophosphate (GGPP) and the KLF2 inducer geranylgeranyl transferase inhibitor (GGTI-298) were used to incubate with neutrophils to investigate the role of KLF2 in the regulation of neutrophil apoptosis. To clarify whether serum from SLE patients affects neutrophil KLF2 expression and apoptosis, sera from SLE patients were collected and used to incubate with neutrophils from HCs, followed by the detection of KLF2 levels and apoptosis levels of neutrophils. Additionally, the correlation between KLF2 levels and SLE disease activity index (SLEDAI) was analyzed. The expression of KLF2 in neutrophils of SLE patients was significantly suppressed, and the decreased KLF2 was associated with the upregulation of neutrophil apoptosis. Moreover, newly diagnosed SLE patients, SLE patients with higher serum IgG and positive anti-Smith antibodies had lower KLF2 expression. Furthermore, we demonstrated that modulating the expression of KLF2 can regulate the apoptosis of neutrophils. The levels of KLF2 in neutrophils were associated with the SLEDAI. In addition, we found that serum from SLE patients could induce apoptosis in neutrophils by down-regulating the expression of KLF2. KLF2 controls the apoptosis of neutrophils and is associated with SLEDAI, which suggests that KLF2 in neutrophils may be involved in the occurrence and development of SLE.
{"title":"KLF2 controls the apoptosis of neutrophils and is associated with disease activity of systemic lupus erythematosus","authors":"Hongshuai Zhao, Zaichuan Lin, Peiwen Zhang, Jiayue Rao, Shumin Xu, Qing Luo, Junming Li","doi":"10.1186/s13075-024-03461-z","DOIUrl":"https://doi.org/10.1186/s13075-024-03461-z","url":null,"abstract":"Neutropenia is more common in patients with systemic lupus erythematosus (SLE) and is a major cause of life-threatening infections. The increased apoptosis of neutrophils is likely to be an essential cause of neutropenia in SLE. However, the detailed mechanisms of increased neutrophil apoptosis in SLE remain unknown. This study focused on the role of Krüppel-like factor 2 (KLF2) in the regulation of neutrophil apoptosis and its association with SLE disease activity. The levels of KLF2 in neutrophils from SLE patients and healthy controls (HCs) were detected by RT-PCR and western blot. The relationship between the levels of KLF2 and the apoptosis levels of neutrophils in SLE patients was analyzed. The KLF2 inhibitor Geranylgeranyl pyrophosphate (GGPP) and the KLF2 inducer geranylgeranyl transferase inhibitor (GGTI-298) were used to incubate with neutrophils to investigate the role of KLF2 in the regulation of neutrophil apoptosis. To clarify whether serum from SLE patients affects neutrophil KLF2 expression and apoptosis, sera from SLE patients were collected and used to incubate with neutrophils from HCs, followed by the detection of KLF2 levels and apoptosis levels of neutrophils. Additionally, the correlation between KLF2 levels and SLE disease activity index (SLEDAI) was analyzed. The expression of KLF2 in neutrophils of SLE patients was significantly suppressed, and the decreased KLF2 was associated with the upregulation of neutrophil apoptosis. Moreover, newly diagnosed SLE patients, SLE patients with higher serum IgG and positive anti-Smith antibodies had lower KLF2 expression. Furthermore, we demonstrated that modulating the expression of KLF2 can regulate the apoptosis of neutrophils. The levels of KLF2 in neutrophils were associated with the SLEDAI. In addition, we found that serum from SLE patients could induce apoptosis in neutrophils by down-regulating the expression of KLF2. KLF2 controls the apoptosis of neutrophils and is associated with SLEDAI, which suggests that KLF2 in neutrophils may be involved in the occurrence and development of SLE.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"12 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849181","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}
Pub Date : 2024-12-19DOI: 10.1186/s13075-024-03450-2
Zijuan Fan, Wenzhu Song, Yan Ke, Ligan Jia, Songyan Li, Jiao Jiao Li, Yuqing Zhang, Jianhao Lin, Bin Wang
To use routine demographic and clinical data to develop an interpretable individual-level machine learning (ML) model to diagnose knee osteoarthritis (KOA) and to identify highly ranked features. In this retrospective, population-based cohort study, anonymized questionnaire data was retrieved from the Wu Chuan KOA Study, Inner Mongolia, China. After feature selections, participants were divided in a 7:3 ratio into training and test sets. Class balancing was applied to the training set for data augmentation. Four ML classifiers were compared by cross-validation within the training set and their performance was further analyzed with an unseen test set. Classifications were evaluated using sensitivity, specificity, positive predictive value, negative predictive value, accuracy, area under the curve(AUC), G-means, and F1 scores. The best model was explained using Shapley values to extract highly ranked features. A total of 1188 participants were investigated in this study, among whom 26.3% were diagnosed with KOA. Comparatively, XGBoost with Boruta exhibited the highest classification performance among the four models, with an AUC of 0.758, G-means of 0.800, and F1 scores of 0.703. The SHAP method reveals the top 17 features of KOA according to the importance ranking, and the average of the experience of joint pain was recognized as the most important features. Our study highlights the usefulness of machine learning in unveiling important factors that influence the diagnosis of KOA to guide new prevention strategies. Further work is needed to validate this approach.
{"title":"XGBoost-SHAP-based interpretable diagnostic framework for knee osteoarthritis: a population-based retrospective cohort study","authors":"Zijuan Fan, Wenzhu Song, Yan Ke, Ligan Jia, Songyan Li, Jiao Jiao Li, Yuqing Zhang, Jianhao Lin, Bin Wang","doi":"10.1186/s13075-024-03450-2","DOIUrl":"https://doi.org/10.1186/s13075-024-03450-2","url":null,"abstract":"To use routine demographic and clinical data to develop an interpretable individual-level machine learning (ML) model to diagnose knee osteoarthritis (KOA) and to identify highly ranked features. In this retrospective, population-based cohort study, anonymized questionnaire data was retrieved from the Wu Chuan KOA Study, Inner Mongolia, China. After feature selections, participants were divided in a 7:3 ratio into training and test sets. Class balancing was applied to the training set for data augmentation. Four ML classifiers were compared by cross-validation within the training set and their performance was further analyzed with an unseen test set. Classifications were evaluated using sensitivity, specificity, positive predictive value, negative predictive value, accuracy, area under the curve(AUC), G-means, and F1 scores. The best model was explained using Shapley values to extract highly ranked features. A total of 1188 participants were investigated in this study, among whom 26.3% were diagnosed with KOA. Comparatively, XGBoost with Boruta exhibited the highest classification performance among the four models, with an AUC of 0.758, G-means of 0.800, and F1 scores of 0.703. The SHAP method reveals the top 17 features of KOA according to the importance ranking, and the average of the experience of joint pain was recognized as the most important features. Our study highlights the usefulness of machine learning in unveiling important factors that influence the diagnosis of KOA to guide new prevention strategies. Further work is needed to validate this approach.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"77 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849128","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}
Pub Date : 2024-12-18DOI: 10.1186/s13075-024-03424-4
Gilson Goncalves dos Santos, Juan Miguel Jiménez-Andrade, Enriqueta Muñoz-Islas, Mariana E. Candanedo-Quiroz, Andrea Gonzalez Cardenas, Bronwen Drummond, Peter Pham, Gwendalynn Stilson, Chao-Chin Hsu, Lauriane Delay, Juliana M. Navia-Pelaez, Julia Paes Lemes, Yury I. Miller, Tony L. Yaksh, Maripat Corr
In the murine K/BxN serum transfer rheumatoid arthritis (RA) model, tactile allodynia persists after resolution of inflammation in male and partially in female wild type (WT) mice, which is absent in Toll-like receptor (TLR)4 deficient animals. We assessed the role of TLR4 on allodynia, bone remodeling and afferent sprouting in this model of arthritis. K/BxN sera were injected into male and female mice with conditional or stable TLR4 deletion and controls. Paw swelling was scored and allodynia assessed by von Frey filaments. At day 28, synovial neural fibers were visualized with confocal microscopy and bone density assayed with microCT. Microglial activity and TLR4 dimerization in spinal cords were examined by immunofluorescence and flow cytometry. In the synovium, K/BxN injected WT male and female mice showed robust increases in calcitonin gene related-peptide (CGRP+), tyrosine hydroxylase (TH)+ and GAP43+ nerve fibers. Trabecular bone density by microCT was significantly decreased in K/BxN WT female but not in WT male mice. The number of osteoclasts increased in both sexes of WT mice, but not in Tlr4-/- K/BxN mice. We used conditional strains with Cre drivers for monocytes/osteoclasts (lysozyme M), microglia (Tmem119 and Cx3CR1), astrocytes (GFAP) and sensory neurons (advillin) for Tlr4f/f disruption. All strains developed similar arthritis scores after K/BxN serum injection with the exception being the Tlr4Tmem119 mice which showed a reduction. Both sexes of Tlr4Lyz2, Tlr4Tmem119 and Tlr4Cx3cr1 mice displayed a partial reversal of the chronic pain phenotype but not in Tlr4Avil, and Tlr4Gfap mice. WT K/BxN male mice showed increases in spinal Iba1, but not GFAP, compared to Tlr4-/- male mice. To determine whether spinal TLR4 was indeed activated in the K/BxN mice, flow cytometry of lumbar spinal cords of WT K/BxN male mice was performed and revealed that TLR4 in microglia cells (CD11b+ /TMEM119+) demonstrated dimerization (e.g. activation) and a characteristic increase in lipid rafts. These results demonstrated a complex chronic allodynia phenotype associated with TLR4 in microglia and monocytic cell lineages, and a parallel spinal TLR4 activation. However, TLR4 is dispensable for the development of peripheral nerve sprouting in this model.
{"title":"Role of TLR4 activation and signaling in bone remodeling, and afferent sprouting in serum transfer arthritis","authors":"Gilson Goncalves dos Santos, Juan Miguel Jiménez-Andrade, Enriqueta Muñoz-Islas, Mariana E. Candanedo-Quiroz, Andrea Gonzalez Cardenas, Bronwen Drummond, Peter Pham, Gwendalynn Stilson, Chao-Chin Hsu, Lauriane Delay, Juliana M. Navia-Pelaez, Julia Paes Lemes, Yury I. Miller, Tony L. Yaksh, Maripat Corr","doi":"10.1186/s13075-024-03424-4","DOIUrl":"https://doi.org/10.1186/s13075-024-03424-4","url":null,"abstract":"In the murine K/BxN serum transfer rheumatoid arthritis (RA) model, tactile allodynia persists after resolution of inflammation in male and partially in female wild type (WT) mice, which is absent in Toll-like receptor (TLR)4 deficient animals. We assessed the role of TLR4 on allodynia, bone remodeling and afferent sprouting in this model of arthritis. K/BxN sera were injected into male and female mice with conditional or stable TLR4 deletion and controls. Paw swelling was scored and allodynia assessed by von Frey filaments. At day 28, synovial neural fibers were visualized with confocal microscopy and bone density assayed with microCT. Microglial activity and TLR4 dimerization in spinal cords were examined by immunofluorescence and flow cytometry. In the synovium, K/BxN injected WT male and female mice showed robust increases in calcitonin gene related-peptide (CGRP+), tyrosine hydroxylase (TH)+ and GAP43+ nerve fibers. Trabecular bone density by microCT was significantly decreased in K/BxN WT female but not in WT male mice. The number of osteoclasts increased in both sexes of WT mice, but not in Tlr4-/- K/BxN mice. We used conditional strains with Cre drivers for monocytes/osteoclasts (lysozyme M), microglia (Tmem119 and Cx3CR1), astrocytes (GFAP) and sensory neurons (advillin) for Tlr4f/f disruption. All strains developed similar arthritis scores after K/BxN serum injection with the exception being the Tlr4Tmem119 mice which showed a reduction. Both sexes of Tlr4Lyz2, Tlr4Tmem119 and Tlr4Cx3cr1 mice displayed a partial reversal of the chronic pain phenotype but not in Tlr4Avil, and Tlr4Gfap mice. WT K/BxN male mice showed increases in spinal Iba1, but not GFAP, compared to Tlr4-/- male mice. To determine whether spinal TLR4 was indeed activated in the K/BxN mice, flow cytometry of lumbar spinal cords of WT K/BxN male mice was performed and revealed that TLR4 in microglia cells (CD11b+ /TMEM119+) demonstrated dimerization (e.g. activation) and a characteristic increase in lipid rafts. These results demonstrated a complex chronic allodynia phenotype associated with TLR4 in microglia and monocytic cell lineages, and a parallel spinal TLR4 activation. However, TLR4 is dispensable for the development of peripheral nerve sprouting in this model.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"23 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840776","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}
Pub Date : 2024-12-13DOI: 10.1186/s13075-024-03451-1
Maren Claus, Merle Freitag, Meike Ewald, Lea Rodon, Franca Deicher, Carsten Watzl, Philipp Kolb, Hanns-Martin Lorenz, Michael Schmitt, Wolfgang Merkt
The high potential of CD19.CAR-T cells to treat autoimmune diseases such as Systemic Sclerosis (SSc) supposedly relies on the disappearance of autoantibodies. Here we investigated effects of CAR-T cells on the innate immune system which is an important contributor to pathology in SSc. Longitudinal analysis of peripheral blood mononuclear cells from an Scl70 + SSc patient treated with CAR-T cells sampled over 18 months by 29-color spectral flow cytometry, in vitro experiments using sera from patient cohorts. In the patient treated with CAR-T cells, the substantial clinical improvement was paralleled by dynamic changes in innate lymphoid cells, namely Fcγ-receptor IIIA-expressing natural killer (NK) cells. NK cells adopted a more juvenile, less activated, and less differentiated phenotype. In parallel, the potency of serum to form Scl70-containing immune complexes that activate Fcγ-receptor IIIA decreased over time. These observations suggested a mechanistic link between reversal of adaptive autoimmunity and recovering Fcγ-receptor IIIA-expressing innate immune cells after CAR-T cell therapy via regressing immune complex activity. Experiments with sera from the non-CAR-T-treated SSc cohort confirmed that Scl70-containing immune complexes activate Fcγ-receptor IIIA-expressing NK cells in a dose-dependent manner, substantiating the relevance of this link between adaptive and innate immunity in SSc. This report describes for the first time the phenotypic recovery of innate Fcγ-receptor-expressing cells in an SSc patient treated with CAR-T cells. Decreasing autoantibody levels associated with a reduced ability to form functional immune complexes, the latter appearing to contribute to pathology in SSc via activation of Fcγ receptor IIIA + cells such as NK cells. Proposed mechanism of involvement of NK cells and soluble Immune Complexes (sICs) in disease progression during active autoimmunity in SSc (left) and resolution of fibrosis after deep B cell depletion by CD19.CAR-T cells and disappearance of autoantibodies (right).
{"title":"Immunological effects of CD19.CAR-T cell therapy in systemic sclerosis: an extended case study","authors":"Maren Claus, Merle Freitag, Meike Ewald, Lea Rodon, Franca Deicher, Carsten Watzl, Philipp Kolb, Hanns-Martin Lorenz, Michael Schmitt, Wolfgang Merkt","doi":"10.1186/s13075-024-03451-1","DOIUrl":"https://doi.org/10.1186/s13075-024-03451-1","url":null,"abstract":"The high potential of CD19.CAR-T cells to treat autoimmune diseases such as Systemic Sclerosis (SSc) supposedly relies on the disappearance of autoantibodies. Here we investigated effects of CAR-T cells on the innate immune system which is an important contributor to pathology in SSc. Longitudinal analysis of peripheral blood mononuclear cells from an Scl70 + SSc patient treated with CAR-T cells sampled over 18 months by 29-color spectral flow cytometry, in vitro experiments using sera from patient cohorts. In the patient treated with CAR-T cells, the substantial clinical improvement was paralleled by dynamic changes in innate lymphoid cells, namely Fcγ-receptor IIIA-expressing natural killer (NK) cells. NK cells adopted a more juvenile, less activated, and less differentiated phenotype. In parallel, the potency of serum to form Scl70-containing immune complexes that activate Fcγ-receptor IIIA decreased over time. These observations suggested a mechanistic link between reversal of adaptive autoimmunity and recovering Fcγ-receptor IIIA-expressing innate immune cells after CAR-T cell therapy via regressing immune complex activity. Experiments with sera from the non-CAR-T-treated SSc cohort confirmed that Scl70-containing immune complexes activate Fcγ-receptor IIIA-expressing NK cells in a dose-dependent manner, substantiating the relevance of this link between adaptive and innate immunity in SSc. This report describes for the first time the phenotypic recovery of innate Fcγ-receptor-expressing cells in an SSc patient treated with CAR-T cells. Decreasing autoantibody levels associated with a reduced ability to form functional immune complexes, the latter appearing to contribute to pathology in SSc via activation of Fcγ receptor IIIA + cells such as NK cells. Proposed mechanism of involvement of NK cells and soluble Immune Complexes (sICs) in disease progression during active autoimmunity in SSc (left) and resolution of fibrosis after deep B cell depletion by CD19.CAR-T cells and disappearance of autoantibodies (right).","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"24 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815701","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}
Pub Date : 2024-12-11DOI: 10.1186/s13075-024-03444-0
Michael Gernert, Tobias Müller, Lukas Schweiker, Marc Schmalzing, Matthias Fröhlich, Lea-Kristin Nagler, Patrick-Pascal Strunz, Hannah Labinsky, Eva Christina Schwaneck
Clonal T cell populations are frequently detected in patients with rheumatic diseases. The relevance of this finding is often uncertain, as the clinical spectrum can range from being asymptomatic to T cell leukemia. Former studies suggested that certain anti-rheumatic drugs might influence the course of the clonal T cell populations. A prospective long-term follow up study was performed including patients with rheumatic diseases and clonal T cell populations. Clinical features, adverse events, especially infections and cytopenias, and immunosuppressive medication were assessed. T cell populations were characterized by polymerase chain reaction, flow cytometry and stimulated cell cultures. 28 Patients with rheumatoid arthritis, spondyloarthritis, or giant cell arteritis were prospectively followed for up to 7.6 years. Severe infections or cytopenias (10.7% autoimmune neutropenias) were rare. The clonal T cell populations mostly persisted over time, the tumor burden decreased in the long-term. The cytokine secretion in stimulated T cell cultures did not differ in the subgroup of RA patients with versus without clonal T cells. Clonal T cell populations in patients with rheumatic diseases are common, but are rarely harmful. Feared neutropenia, infections or progression into T cell leukemia could not be detected in the long-term in our cohort.
{"title":"Clonal T cell populations scarcely impair patients with rheumatic diseases: a prospective long-term follow up study","authors":"Michael Gernert, Tobias Müller, Lukas Schweiker, Marc Schmalzing, Matthias Fröhlich, Lea-Kristin Nagler, Patrick-Pascal Strunz, Hannah Labinsky, Eva Christina Schwaneck","doi":"10.1186/s13075-024-03444-0","DOIUrl":"https://doi.org/10.1186/s13075-024-03444-0","url":null,"abstract":"Clonal T cell populations are frequently detected in patients with rheumatic diseases. The relevance of this finding is often uncertain, as the clinical spectrum can range from being asymptomatic to T cell leukemia. Former studies suggested that certain anti-rheumatic drugs might influence the course of the clonal T cell populations. A prospective long-term follow up study was performed including patients with rheumatic diseases and clonal T cell populations. Clinical features, adverse events, especially infections and cytopenias, and immunosuppressive medication were assessed. T cell populations were characterized by polymerase chain reaction, flow cytometry and stimulated cell cultures. 28 Patients with rheumatoid arthritis, spondyloarthritis, or giant cell arteritis were prospectively followed for up to 7.6 years. Severe infections or cytopenias (10.7% autoimmune neutropenias) were rare. The clonal T cell populations mostly persisted over time, the tumor burden decreased in the long-term. The cytokine secretion in stimulated T cell cultures did not differ in the subgroup of RA patients with versus without clonal T cells. Clonal T cell populations in patients with rheumatic diseases are common, but are rarely harmful. Feared neutropenia, infections or progression into T cell leukemia could not be detected in the long-term in our cohort.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"19 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804614","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}
Pub Date : 2024-12-05DOI: 10.1186/s13075-024-03449-9
Ronja Ramien, Tatjana Rudi, Rieke Alten, Andreas Krause, Matthias Schneider, Martin Schaefer, Anja Strangfeld, Yvette Meissner
To investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). We analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months. We identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of > 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97–1.40] and 1.06 [0.86–1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35–2.57]) and log CRP (1.55 [1.21–1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings. Higher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient’s global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.
{"title":"Impact of systemic inflammation and disease activity on the incidence of interstitial lung disease in patients with rheumatoid arthritis – a nested case-control study within the German biologics register RABBIT","authors":"Ronja Ramien, Tatjana Rudi, Rieke Alten, Andreas Krause, Matthias Schneider, Martin Schaefer, Anja Strangfeld, Yvette Meissner","doi":"10.1186/s13075-024-03449-9","DOIUrl":"https://doi.org/10.1186/s13075-024-03449-9","url":null,"abstract":"To investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). We analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months. We identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of > 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97–1.40] and 1.06 [0.86–1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35–2.57]) and log CRP (1.55 [1.21–1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings. Higher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient’s global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"1 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776643","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}
Pub Date : 2024-12-03DOI: 10.1186/s13075-024-03443-1
Paloma Palm von Alten Blaskowitz, Anna-Maria Liphardt, Claudia Bouzas, Birte Coppers, Pascal Petit, Nicolas Vuillerme, Vanessa Bundle, Sebastian Rudolf, Johannes Knitza, Maria Gabriella Raimondo, Hannah Labinsky, Lukas Hatscher, Andreas Wirsching, Daniela Bohr, Elizabeth Araujo, Andreas Ramming, Alina Ramming, Georg Schett, Harriet Morf
Spondyloarthritides (SpAs) are a group of common rheumatic diseases that often cause limited mobility and lower back pain. Physiotherapy is an integral part of treatment, but access to physiotherapy limits treatment success. Digital health applications (DHAs) enable home-based physiotherapy and could significantly improve access for SpAs patients. The aim is to investigate the clinical effects of the DHA ViViRA compared with those of standard physiotherapy. SpAs patients with chronic back pain were enrolled in a randomized controlled trial. The intervention group received ViViRA DHA, whereas the control group received standard physiotherapy. Pain (verbal rating scale, PAIN-Detect), quality of life (SF-36) and mobility (BASMI) were assessed at baseline and after 12 weeks as the primary outcomes. Data from 59 participants (71.2% female, mean age 45.2 years) were analyzed. The intervention group showed a significant improvement in mobility (average BASMI score: baseline: 1.1 [range 0.7–1.5]; follow-up: 1.0 [range 0.5–1.4]; p = 0.05), whereas the control group showed a significant decrease in mobility (baseline: 1.5 [range 1.1–1.9]; follow-up: 1.8 [range 1.4–2.2]; p = 0.00). The intervention group demonstrated lower pain intensity (VRS pain level at week 3.5 ± 2.8) than did the control group (VRS pain level at week 4.5 ± 2) after 12 weeks. Our results highlight the efficacy of DHAs such as ViViRA in the treatment of lower back pain in SpAs patients. Compared with the current gold standard, physiotherapy, DHA use results in superior outcomes. However, further larger studies are needed to confirm these promising results. The study is registered in the German clinical trial registry (DRKS) under the following ID: DRKS00031254.
{"title":"Impact of the digital health application ViViRA on spinal mobility, physical function, quality of life and pain perception in spondyloarthritides patients: a randomized controlled trial","authors":"Paloma Palm von Alten Blaskowitz, Anna-Maria Liphardt, Claudia Bouzas, Birte Coppers, Pascal Petit, Nicolas Vuillerme, Vanessa Bundle, Sebastian Rudolf, Johannes Knitza, Maria Gabriella Raimondo, Hannah Labinsky, Lukas Hatscher, Andreas Wirsching, Daniela Bohr, Elizabeth Araujo, Andreas Ramming, Alina Ramming, Georg Schett, Harriet Morf","doi":"10.1186/s13075-024-03443-1","DOIUrl":"https://doi.org/10.1186/s13075-024-03443-1","url":null,"abstract":"Spondyloarthritides (SpAs) are a group of common rheumatic diseases that often cause limited mobility and lower back pain. Physiotherapy is an integral part of treatment, but access to physiotherapy limits treatment success. Digital health applications (DHAs) enable home-based physiotherapy and could significantly improve access for SpAs patients. The aim is to investigate the clinical effects of the DHA ViViRA compared with those of standard physiotherapy. SpAs patients with chronic back pain were enrolled in a randomized controlled trial. The intervention group received ViViRA DHA, whereas the control group received standard physiotherapy. Pain (verbal rating scale, PAIN-Detect), quality of life (SF-36) and mobility (BASMI) were assessed at baseline and after 12 weeks as the primary outcomes. Data from 59 participants (71.2% female, mean age 45.2 years) were analyzed. The intervention group showed a significant improvement in mobility (average BASMI score: baseline: 1.1 [range 0.7–1.5]; follow-up: 1.0 [range 0.5–1.4]; p = 0.05), whereas the control group showed a significant decrease in mobility (baseline: 1.5 [range 1.1–1.9]; follow-up: 1.8 [range 1.4–2.2]; p = 0.00). The intervention group demonstrated lower pain intensity (VRS pain level at week 3.5 ± 2.8) than did the control group (VRS pain level at week 4.5 ± 2) after 12 weeks. Our results highlight the efficacy of DHAs such as ViViRA in the treatment of lower back pain in SpAs patients. Compared with the current gold standard, physiotherapy, DHA use results in superior outcomes. However, further larger studies are needed to confirm these promising results. The study is registered in the German clinical trial registry (DRKS) under the following ID: DRKS00031254.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"136 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760072","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}
Pub Date : 2024-12-02DOI: 10.1186/s13075-024-03446-y
Antonella Notarnicola, Charlotta Preger, Susanna L. Lundström, Nuria Renard, Edvard Wigren, Eveline Van Gompel, Angeles S. Galindo-Feria, Helena Persson, Maryam Fathi, Johan Grunewald, Per-Johan Jakobsson, Susanne Gräslund, Ingrid E. Lundberg, Cátia Fernandes-Cerqueira
<p><b>Correction</b><b>: </b><b>Arthritis Res Ther 24, 62 (2022)</b></p><p><b>https://doi.org/10.1186/s13075-022-02745-6</b></p><br/><p>Following publication of the original article [1], we have recently received a comment by PubPeer that has found a mistake in our Figure 1 D. The western blot image uploaded for patient P16 was by mistake the same as for patient P15. It was only when putting together the image that the error occurred and all calculations, results and conclusions are thus unchanged. We have now updated figure 1 in the publication with the correct image.</p><p>Incorrect figure 1.</p><figure><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13075-024-03446-y/MediaObjects/13075_2024_3446_Figa_HTML.png?as=webp" type="image/webp"/><img alt="figure a" aria-describedby="Figa" height="740" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13075-024-03446-y/MediaObjects/13075_2024_3446_Figa_HTML.png" width="685"/></picture></figure><p>Correct figure 1.</p><figure><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13075-024-03446-y/MediaObjects/13075_2024_3446_Figb_HTML.png?as=webp" type="image/webp"/><img alt="figure b" aria-describedby="Figb" height="738" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13075-024-03446-y/MediaObjects/13075_2024_3446_Figb_HTML.png" width="685"/></picture></figure><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Notarnicola A, Preger C, Lundström SL, et al. Longitudinal assessment of reactivity and affinity profile of anti-Jo1 autoantibodies to distinct HisRS domains and a splice variant in a cohort of patients with myositis and anti-synthetase syndrome. Arthritis Res Ther. 2022;24:62. https://doi.org/10.1186/s13075-022-02745-6.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><span>Author notes</span><ol><li><p>Antonella Notarnicola, Charlotta Preger, Ingrid E. Lundberg and Cátia Fernandes-Cerqueira contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Division of Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, 171 64, Solna, Stockholm, Sweden</p><p>Antonella Notarnicola, Charlotta Preger, Nuria Renard, Edvard Wigren, Eveline Van Gompel, Angeles S. Galindo-Feria, Per-Johan Jakobsson, Susanne Gräslund, Ingrid E. Lundberg & Cátia Fernandes-Cerqueira</p></li><li><p>Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden</p><p>Antonella Notarnicola, Charlotta Preger, Nuria Renard, Edvard Wigren, Eveline Van Gompel, Angeles S. Galindo-Feria, Johan Grunewald
更正：Arthritis Res Ther 24,62 (2022)https://doi.org/10.1186/s13075-022-02745-6Following原文b[1]发表后，我们最近收到PubPeer的评论，发现我们的图1 d中存在错误。患者P16上传的western blot图像与患者P15错误相同。只有在将图像组合在一起时才会出现错误，因此所有的计算、结果和结论都不会改变。我们现在用正确的图像更新了出版物中的图1。错误的图1。正确的图1。notannicola A, Preger C, Lundström SL，等。在肌炎和抗合成酶综合征患者队列中，抗jo1自身抗体对不同HisRS结构域和剪接变异体的反应性和亲和力的纵向评估关节炎杂志，2022;24:62。https://doi.org/10.1186/s13075-022-02745-6.Article CAS PubMed PubMed Central谷歌学者下载参考作者说明antonella Notarnicola， Charlotta Preger, Ingrid E. Lundberg和Cátia Fernandes-Cerqueira对这项工作也做出了同样的贡献。作者与单位：卡罗林斯卡医学院附属卡罗林斯卡大学医院内科风湿病科，1764年，斯德哥尔摩索尔纳，瑞典antonella Notarnicola， Charlotta Preger, Nuria Renard, edward Wigren, Eveline Van Gompel, Angeles S. Galindo-Feria, Per-Johan Jakobsson, Susanne Gräslund, Ingrid E. Lundberg &；Cátia瑞典斯德哥尔摩卡罗林斯卡医学院分子医学中心antonella Notarnicola， Charlotta Preger, Nuria Renard, edward Wigren, Eveline Van Gompel, Angeles S. Galindo-Feria, Johan Grunewald, Per-Johan Jakobsson, Susanne Gräslund, Ingrid E. Lundberg &；Cátia fernandes - cerqueira结构基因组学联盟，多伦多，加拿大Susanne GräslundDivision，卡罗林斯卡医学院医学生物化学与生物物理系，Solnavägen 9, 171 77，瑞典斯德哥尔摩；susanna L. LundströmLaboratory，组织同源性-疾病，骨骼生物学与工程研究中心，比利时鲁汶，鲁汶；meveline Van gompell生命科学实验室，药物发现与开发，瑞典斯德哥尔摩；helena persson化学、生物技术与健康工程科学学院；瑞典斯德哥尔摩皇家理工学院（KTH）呼吸医学和过敏科，J7:30，瑞典斯德哥尔摩卡罗林斯卡医学院附属卡罗林斯卡大学医院生物临床部，SE-171 76Johan grunewald4 cell, 14 Rue de La Beaune, 93100，蒙特勒伊FranceCatia Fernandes-CerqueiraAuthorsAntonella NotarnicolaView publicationsYou作者也可以搜索PubMed的作者在谷歌ScholarCharlotta PregerView publicationsYou作者也可以搜索PubMed的作者在谷歌ScholarSusanna l . LundstromView publicationsYou作者也可以搜索PubMed的作者在谷歌ScholarNuria RenardView publicationsYou作者也可以搜索PubMed的作者在谷歌ScholarEdvard WigrenView publicationsYou作者也可以搜索在PubMed谷歌ScholarEveline Van GompelView作者出版物您也可以在PubMed谷歌ScholarAngeles S. galindoferiview作者出版物中搜索此作者您也可以在PubMed谷歌ScholarHelena personsonview作者出版物中搜索此作者您也可以在PubMed谷歌ScholarMaryam FathiView作者出版物中搜索此作者您也可以在PubMed谷歌ScholarJohan GrunewaldView作者出版物中搜索此作者您也可以搜索PubMed的作者在谷歌ScholarPer-Johan JakobssonView publicationsYou作者也可以搜索PubMed的作者在谷歌ScholarSusanne GraslundView publicationsYou作者也可以搜索PubMed的作者在谷歌ScholarIngrid大肠LundbergView publicationsYou作者也可以搜索PubMed的作者在谷歌ScholarCatia Fernandes-CerqueiraView publicationsYou作者也可以搜索PubMed的作者在谷歌ScholarCorresponding authorCorrespondence安东内拉·Notarnicola·拉斯泰利。开放获取本文遵循知识共享署名4.0国际许可协议，该协议允许以任何媒介或格式使用、共享、改编、分发和复制，只要您适当地注明原作者和来源，提供知识共享许可协议的链接，并注明是否进行了更改。本文中的图像或其他第三方材料包含在文章的知识共享许可协议中，除非在材料的署名中另有说明。如果材料未包含在文章的知识共享许可中，并且您的预期用途不被法律法规允许或超过允许的用途，您将需要直接获得版权所有者的许可。要查看本许可的副本，请访问http://creativecommons.org/licenses/by/4.0/。 知识共享公共领域免责条款（http://creativecommons.org/publicdomain/zero/1.0/）适用于本文中提供的数据，除非在数据的署名中另有说明。转载和许可引用本文：otarnicola， A., Preger， C., Lundström， S.L.等。更正：在肌炎和抗合成酶综合征患者队列中，对抗jo1自身抗体对不同HisRS结构域和剪接变异体的反应性和亲和力进行纵向评估。关节炎杂志26,206（2024）。https://doi.org/10.1186/s13075-024-03446-yDownload citationpublishing: 02 December 2024DOI: https://doi.org/10.1186/s13075-024-03446-yShare这篇文章任何你分享以下链接的人都可以阅读到这篇文章：获取可共享链接对不起，这篇文章目前没有可共享的链接。复制到剪贴板由施普林格自然共享内容倡议提供
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