Ching-Yao Lai, Su-Boon Yong, Liang-Chun Shih, James ChengChung Wei
<p>The advent of chimeric antigen receptor (CAR) T-cell therapy is redefining therapeutic boundaries in severe, treatment-refractory autoimmune diseases. Originally developed for hematologic malignancies, CAR T-cell therapy is now emerging as a transformative intervention for systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies, and systemic sclerosis. A comprehensive review by Chung et al. aptly synthesizes this evolving field and situates CAR T-cell therapy at the frontier of immune modulation in autoimmunity [<span>1</span>].</p><p>B-cell-directed therapies have long formed the cornerstone of treatment for many autoimmune conditions. However, agents such as rituximab, targeting CD20, achieve only partial B-cell depletion and are often insufficient in inducing sustained remission, especially in tissue-compartmentalized disease [<span>1</span>]. CAR T-cells targeting CD19—expressed across a broader B-cell lineage including plasmablasts—have demonstrated not only profound B-cell depletion but also rapid seroconversion and sustained drug-free remission in early clinical studies [<span>2, 3</span>]. Unlike monoclonal antibodies, CAR T-cells represent a living drug, with the capacity to traffic to inflamed sites and eliminate pathogenic cells with high efficiency.</p><p>CAR T-cells differ fundamentally from passive antibody therapies. Once infused, they expand, persist, and actively target disease-driving B-cells, particularly in sanctuary sites that are often resistant to conventional therapies. Evidence from multiple studies indicates that anti-CD19 CAR T-cell infusion can induce rapid and profound B-cell aplasia, leading to seroconversion to autoantibody negativity and sustained clinical remission in conditions previously resistant to treatment [<span>2, 3</span>]. This durable therapeutic effect underpins the concept of immune reprogramming rather than suppression.</p><p>The profound efficacy of this “living drug”, however, is matched by an equally profound need to understand its safety. Concerns regarding safety, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), persist. However, clinical data from autoimmune populations have thus far demonstrated a more favorable safety profile, potentially due to lower target burden and refined CAR constructs [<span>1, 4</span>]. Design modifications—such as incorporation of CD8α-derived hinge and transmembrane domains in place of CD28-derived motifs—have been shown to reduce pro-inflammatory cytokine release while preserving cytotoxic efficacy [<span>5</span>]. These engineering advances are essential for applying CAR T-cell therapy in non-malignant diseases, where the therapeutic margin must be wide. Nevertheless, vigilance is paramount. The long-term consequences of profound, albeit transient, B-cell depletion require systematic monitoring, and the potential for rare but serious toxicities cannot be dismissed.</p><p>Efforts ar
{"title":"Editorial: Is CAR T-Cell Therapy the Immunological Reset Autoimmunity Needs?","authors":"Ching-Yao Lai, Su-Boon Yong, Liang-Chun Shih, James ChengChung Wei","doi":"10.1111/1756-185x.70552","DOIUrl":"10.1111/1756-185x.70552","url":null,"abstract":"<p>The advent of chimeric antigen receptor (CAR) T-cell therapy is redefining therapeutic boundaries in severe, treatment-refractory autoimmune diseases. Originally developed for hematologic malignancies, CAR T-cell therapy is now emerging as a transformative intervention for systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies, and systemic sclerosis. A comprehensive review by Chung et al. aptly synthesizes this evolving field and situates CAR T-cell therapy at the frontier of immune modulation in autoimmunity [<span>1</span>].</p><p>B-cell-directed therapies have long formed the cornerstone of treatment for many autoimmune conditions. However, agents such as rituximab, targeting CD20, achieve only partial B-cell depletion and are often insufficient in inducing sustained remission, especially in tissue-compartmentalized disease [<span>1</span>]. CAR T-cells targeting CD19—expressed across a broader B-cell lineage including plasmablasts—have demonstrated not only profound B-cell depletion but also rapid seroconversion and sustained drug-free remission in early clinical studies [<span>2, 3</span>]. Unlike monoclonal antibodies, CAR T-cells represent a living drug, with the capacity to traffic to inflamed sites and eliminate pathogenic cells with high efficiency.</p><p>CAR T-cells differ fundamentally from passive antibody therapies. Once infused, they expand, persist, and actively target disease-driving B-cells, particularly in sanctuary sites that are often resistant to conventional therapies. Evidence from multiple studies indicates that anti-CD19 CAR T-cell infusion can induce rapid and profound B-cell aplasia, leading to seroconversion to autoantibody negativity and sustained clinical remission in conditions previously resistant to treatment [<span>2, 3</span>]. This durable therapeutic effect underpins the concept of immune reprogramming rather than suppression.</p><p>The profound efficacy of this “living drug”, however, is matched by an equally profound need to understand its safety. Concerns regarding safety, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), persist. However, clinical data from autoimmune populations have thus far demonstrated a more favorable safety profile, potentially due to lower target burden and refined CAR constructs [<span>1, 4</span>]. Design modifications—such as incorporation of CD8α-derived hinge and transmembrane domains in place of CD28-derived motifs—have been shown to reduce pro-inflammatory cytokine release while preserving cytotoxic efficacy [<span>5</span>]. These engineering advances are essential for applying CAR T-cell therapy in non-malignant diseases, where the therapeutic margin must be wide. Nevertheless, vigilance is paramount. The long-term consequences of profound, albeit transient, B-cell depletion require systematic monitoring, and the potential for rare but serious toxicities cannot be dismissed.</p><p>Efforts ar","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1756-185x.70552","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Systemic lupus erythematosus (SLE) exhibits diverse clinical presentations and requires regionally specific management strategies. Building upon established international guidelines, the Taiwan College of Rheumatology developed the first set of recommendations for SLE management to focus on the unmet needs of clinical practice in Taiwan. This consensus aims to empower healthcare professionals and optimize patient outcomes in Taiwan. Rheumatologists from various practicing institutions formed a 15-member panel and, through a modified Delphi process, developed consensus statements that encompass various aspects of SLE care in Taiwan, including screening and diagnosis, disease monitoring, treatment strategies, and pregnancy. The expert panel reviewed and refined statements through two meetings with anonymous voting based on a 5-point Likert scale. Consensus is defined as ≥ 75% agreement to the proposed statements. In total, 32 statements achieved consensus. These statements incorporate the latest scientific evidence with insights from Taiwanese experts to address the unique disease characteristics and challenges faced by patients in the region, and could serve as a guide to specialists, family physicians, specialty nurses, and other healthcare professionals in Taiwan for the management of SLE.
{"title":"The Taiwan College of Rheumatology Consensus for the Management of Systemic Lupus Erythematosus","authors":"Wen-Nan Huang, Ming-Han Chen, Song-Chou Hsieh, Ling-Ying Lu, Yeong-Jian Jan Wu, Chang-Youh Tsai, Tsu-Yi Hsieh, Yao-Fan Fang, Fu-Chiang Yeh, Yu-Jih Su, Yu-Wan Liao, Tai-Ju Lee, Heh-Shiang Sheu, Der-Yuan Chen, Shue-Fen Luo","doi":"10.1111/1756-185x.70530","DOIUrl":"10.1111/1756-185x.70530","url":null,"abstract":"<div>\u0000 \u0000 <p>Systemic lupus erythematosus (SLE) exhibits diverse clinical presentations and requires regionally specific management strategies. Building upon established international guidelines, the Taiwan College of Rheumatology developed the first set of recommendations for SLE management to focus on the unmet needs of clinical practice in Taiwan. This consensus aims to empower healthcare professionals and optimize patient outcomes in Taiwan. Rheumatologists from various practicing institutions formed a 15-member panel and, through a modified Delphi process, developed consensus statements that encompass various aspects of SLE care in Taiwan, including screening and diagnosis, disease monitoring, treatment strategies, and pregnancy. The expert panel reviewed and refined statements through two meetings with anonymous voting based on a 5-point Likert scale. Consensus is defined as ≥ 75% agreement to the proposed statements. In total, 32 statements achieved consensus. These statements incorporate the latest scientific evidence with insights from Taiwanese experts to address the unique disease characteristics and challenges faced by patients in the region, and could serve as a guide to specialists, family physicians, specialty nurses, and other healthcare professionals in Taiwan for the management of SLE.</p>\u0000 </div>","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989252","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}
{"title":"Gouty Arthritis With Normouricaemia and Diffuse Urate Deposition","authors":"Wantai Dang","doi":"10.1111/1756-185x.70546","DOIUrl":"10.1111/1756-185x.70546","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965924","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}
Merna Adly, Vimal H. Prajapati, Rebeka Stevenson, Brendan C. Lethebe, Nadia J. Luca
{"title":"Disease Course and Risk of Relapse in Juvenile Localized Scleroderma: A Single-Center Retrospective Study","authors":"Merna Adly, Vimal H. Prajapati, Rebeka Stevenson, Brendan C. Lethebe, Nadia J. Luca","doi":"10.1111/1756-185x.70520","DOIUrl":"10.1111/1756-185x.70520","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933139","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}
Yen, F.S., Y.H. Lee, P. Kuo, M.C. Wu and P.Y. Leong. 2025. “Anti-Inflammatory Mechanisms of Antidiabetic Therapies: Metabolic Regulation and Inflammatory Pathways.” International Journal of Rheumatic Diseases 28, no. 4: e70201.
In the above article, both Poi Kuo and Pui-Ying Leong were listed as the corresponding authors. The corresponding author should be Pui-Ying Leong only.
{"title":"Correction to “Anti-Inflammatory Mechanisms of Antidiabetic Therapies: Metabolic Regulation and Inflammatory Pathways”","authors":"","doi":"10.1111/1756-185x.70544","DOIUrl":"10.1111/1756-185x.70544","url":null,"abstract":"<p>Yen, F.S., Y.H. Lee, P. Kuo, M.C. Wu and P.Y. Leong. 2025. “Anti-Inflammatory Mechanisms of Antidiabetic Therapies: Metabolic Regulation and Inflammatory Pathways.” <i>International Journal of Rheumatic Diseases</i> 28, no. 4: e70201.</p><p>In the above article, both Poi Kuo and Pui-Ying Leong were listed as the corresponding authors. The corresponding author should be Pui-Ying Leong only.</p><p>The online article has been corrected.</p><p>We apologize for this error.</p>","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1756-185x.70544","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ashish Chandwani, J. Sankar, Saba Pravez, Neeti Goyal, Rajeev Chugh, Harsh Jain, Nidhi Goel, Abhishek Kumar, Kartik Sivasami, Vivek Vasdev
{"title":"An Enigmatic Link Between Arthritis and Dysphagia in an Elderly Male!","authors":"Ashish Chandwani, J. Sankar, Saba Pravez, Neeti Goyal, Rajeev Chugh, Harsh Jain, Nidhi Goel, Abhishek Kumar, Kartik Sivasami, Vivek Vasdev","doi":"10.1111/1756-185x.70540","DOIUrl":"10.1111/1756-185x.70540","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917540","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}
<p>Recent advances in immunometabolism and rheumatology have highlighted the role of gut-derived signals in modulating joint health. In particular, Yang et al. proposed that osteoarthritis (OA) may be influenced by intestinal bile acid metabolism through a mechanistic cascade involving the gut microbiota, Glycoursodeoxycholic acid (GUDCA), intestinal Farnesoid X receptor (FXR), and Glucagon-like peptide 1 (GLP-1) signaling. This emerging gut-to-joint communication axis invites new thinking about the pathogenesis and treatment of rheumatic diseases.</p><p>The gut microbiome plays a crucial role in regulating systemic immunity and metabolism, primarily through its modulation of the bile acid (BA) pool. It influences the composition and transformation of both primary and secondary bile acids. This process was previously thought to occur only in the liver, but recent studies have shown that gut bacteria also perform these transformations, increasing the diversity of bile acids [<span>1-3</span>]. Secondary bile acids play crucial roles in modulating immune cell function and differentiation, impacting systemic immunity [<span>4</span>]. Recent findings further suggest that bile acids act as immunoregulatory signals in the gut environment, shaping both innate and adaptive immune responses by promoting regulatory T cell differentiation and suppressing pro-inflammatory T helper cell development [<span>5</span>].</p><p>GUDCA is a conjugated bile acid formed by the glycine-conjugation of the secondary bile acid ursodeoxycholic acid (UDCA). FXR, a nuclear receptor expressed in the liver and intestine, plays a vital role in regulating bile acid homeostasis, lipid metabolism, and intestinal barrier function. When antagonized by GUDCA in the ileum, FXR activity is reduced, resulting in upregulation of pro-secretory hormones such as Glucagon-like peptide-1 (GLP-1) from enteroendocrine L-cells [<span>1</span>]. Yan et al. explored this feedback and found that GUDCA-induced inhibition of intestinal FXR significantly boosted GLP-1 levels and improved gut barrier function and glucose metabolism in diabetic mouse models [<span>6</span>].</p><p>GLP-1, predominantly released by intestinal L-cells upon food consumption, while primarily known for its insulinotropic effects, also exerts anti-inflammatory and neuroprotective functions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of therapeutic agents commonly prescribed for managing type 2 diabetes (T2D). Examples include exenatide, liraglutide, and semaglutide. These drugs exert their effects by imitating the activity of the naturally produced hormone GLP-1 [<span>7</span>]. Recent studies suggest that GLP-1RA may reduce joint inflammation through modulation of local immune responses [<span>8, 9</span>]. Yang et al. showed that targeting the gut-joint axis through FXR inhibition and GLP-1 modulation in osteoarthritis models led to pain reduction and improved joint pathology, hinting at the therapeuti
{"title":"Reframing Osteoarthritis Therapy Through the Gut–GUDCA–FXR–GLP1 Pathway: Opportunities and Limitations","authors":"Shangqi Guan, Yifang Mei","doi":"10.1111/1756-185x.70535","DOIUrl":"10.1111/1756-185x.70535","url":null,"abstract":"<p>Recent advances in immunometabolism and rheumatology have highlighted the role of gut-derived signals in modulating joint health. In particular, Yang et al. proposed that osteoarthritis (OA) may be influenced by intestinal bile acid metabolism through a mechanistic cascade involving the gut microbiota, Glycoursodeoxycholic acid (GUDCA), intestinal Farnesoid X receptor (FXR), and Glucagon-like peptide 1 (GLP-1) signaling. This emerging gut-to-joint communication axis invites new thinking about the pathogenesis and treatment of rheumatic diseases.</p><p>The gut microbiome plays a crucial role in regulating systemic immunity and metabolism, primarily through its modulation of the bile acid (BA) pool. It influences the composition and transformation of both primary and secondary bile acids. This process was previously thought to occur only in the liver, but recent studies have shown that gut bacteria also perform these transformations, increasing the diversity of bile acids [<span>1-3</span>]. Secondary bile acids play crucial roles in modulating immune cell function and differentiation, impacting systemic immunity [<span>4</span>]. Recent findings further suggest that bile acids act as immunoregulatory signals in the gut environment, shaping both innate and adaptive immune responses by promoting regulatory T cell differentiation and suppressing pro-inflammatory T helper cell development [<span>5</span>].</p><p>GUDCA is a conjugated bile acid formed by the glycine-conjugation of the secondary bile acid ursodeoxycholic acid (UDCA). FXR, a nuclear receptor expressed in the liver and intestine, plays a vital role in regulating bile acid homeostasis, lipid metabolism, and intestinal barrier function. When antagonized by GUDCA in the ileum, FXR activity is reduced, resulting in upregulation of pro-secretory hormones such as Glucagon-like peptide-1 (GLP-1) from enteroendocrine L-cells [<span>1</span>]. Yan et al. explored this feedback and found that GUDCA-induced inhibition of intestinal FXR significantly boosted GLP-1 levels and improved gut barrier function and glucose metabolism in diabetic mouse models [<span>6</span>].</p><p>GLP-1, predominantly released by intestinal L-cells upon food consumption, while primarily known for its insulinotropic effects, also exerts anti-inflammatory and neuroprotective functions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of therapeutic agents commonly prescribed for managing type 2 diabetes (T2D). Examples include exenatide, liraglutide, and semaglutide. These drugs exert their effects by imitating the activity of the naturally produced hormone GLP-1 [<span>7</span>]. Recent studies suggest that GLP-1RA may reduce joint inflammation through modulation of local immune responses [<span>8, 9</span>]. Yang et al. showed that targeting the gut-joint axis through FXR inhibition and GLP-1 modulation in osteoarthritis models led to pain reduction and improved joint pathology, hinting at the therapeuti","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1756-185x.70535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This systematic review analyzed 123 adult-onset cases of anti-mitochondrial antibody-positive myositis with cardiac evaluation. Cardiac involvement was frequent, often refractory to immunosuppressive therapy, and commonly required electronic cardiac devices, highlighting the need for early recognition and proactive cardiac monitoring in this rare and distinct myositis subtype.
{"title":"Anti-Mitochondrial Antibody-Positive Myositis: Analyses of 123 Adult-Onset Cases With Cardiac Evaluation","authors":"Tomoyuki Mutoh, Mikihiro Takahashi, Hiroshi Fujii","doi":"10.1111/1756-185x.70543","DOIUrl":"10.1111/1756-185x.70543","url":null,"abstract":"<p>This systematic review analyzed 123 adult-onset cases of anti-mitochondrial antibody-positive myositis with cardiac evaluation. Cardiac involvement was frequent, often refractory to immunosuppressive therapy, and commonly required electronic cardiac devices, highlighting the need for early recognition and proactive cardiac monitoring in this rare and distinct myositis subtype.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917597","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}
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