Pub Date : 2024-05-21DOI: 10.1038/s41584-024-01127-3
Ennio Lubrano, Fabio Massimo Perrotta
Guidelines for the management of psoriatic arthritis (PsA) need to undergo revision to take on board new evidence, particularly in relation to therapeutics. In March 2024, EULAR published updated recommendations for the pharmacological treatment of PsA, and an expert group published consensus statements intended to complement existing guidelines.
{"title":"Two sides of management recommendations for psoriatic arthritis","authors":"Ennio Lubrano, Fabio Massimo Perrotta","doi":"10.1038/s41584-024-01127-3","DOIUrl":"10.1038/s41584-024-01127-3","url":null,"abstract":"Guidelines for the management of psoriatic arthritis (PsA) need to undergo revision to take on board new evidence, particularly in relation to therapeutics. In March 2024, EULAR published updated recommendations for the pharmacological treatment of PsA, and an expert group published consensus statements intended to complement existing guidelines.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 7","pages":"397-398"},"PeriodicalIF":29.4,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141073841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-17DOI: 10.1038/s41584-024-01126-4
Ali Mobasheri, Richard Loeser
Understanding the molecular endotypes that influence clinical phenotypes is a critical step for the stratification of patients with osteoarthritis (OA) into therapeutic subtypes that can help the development of targeted disease-modifying OA drugs (DMOADs) to provide genuine, long-term clinical benefit.
了解影响临床表型的分子内型是将骨关节炎（OA）患者分层为治疗亚型的关键一步，有助于开发有针对性的疾病修饰性 OA 药物（DMOADs），以提供真正的长期临床益处。
{"title":"Clinical phenotypes, molecular endotypes and theratypes in OA therapeutic development","authors":"Ali Mobasheri, Richard Loeser","doi":"10.1038/s41584-024-01126-4","DOIUrl":"10.1038/s41584-024-01126-4","url":null,"abstract":"Understanding the molecular endotypes that influence clinical phenotypes is a critical step for the stratification of patients with osteoarthritis (OA) into therapeutic subtypes that can help the development of targeted disease-modifying OA drugs (DMOADs) to provide genuine, long-term clinical benefit.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 9","pages":"525-526"},"PeriodicalIF":29.4,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.1038/s41584-024-01123-7
Jason S. Knight, Maria G. Tektonidou
The management of antiphospholipid syndrome is hindered by heterogeneous clinical presentations. Whole-blood transcriptomics have the potential to identify previously unknown disease endotypes, which could inform new treatment strategies. However, such hypothesis-generating data must still account for the results of randomized clinical trials, such as those focused on direct oral anticoagulants in APS.
{"title":"Can transcriptomics guide the management of SLE-associated APS?","authors":"Jason S. Knight, Maria G. Tektonidou","doi":"10.1038/s41584-024-01123-7","DOIUrl":"10.1038/s41584-024-01123-7","url":null,"abstract":"The management of antiphospholipid syndrome is hindered by heterogeneous clinical presentations. Whole-blood transcriptomics have the potential to identify previously unknown disease endotypes, which could inform new treatment strategies. However, such hypothesis-generating data must still account for the results of randomized clinical trials, such as those focused on direct oral anticoagulants in APS.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 8","pages":"457-458"},"PeriodicalIF":29.4,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140949616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-13DOI: 10.1038/s41584-024-01118-4
Rachel C. Nordberg, Benjamin J. Bielajew, Takumi Takahashi, Shuyan Dai, Jerry C. Hu, Kyriacos A. Athanasiou
Articular cartilage was expected to be one of the first successfully engineered tissues, but today, cartilage repair products are few and they exhibit considerable limitations. For example, of the cell-based products that are available globally, only one is marketed for non-knee indications, none are indicated for severe osteoarthritis or rheumatoid arthritis, and only one is approved for marketing in the USA. However, advances in cartilage tissue engineering might now finally lead to the development of new cartilage repair products. To understand the potential in this field, it helps to consider the current landscape of tissue-engineered products for articular cartilage repair and particularly cell-based therapies. Advances relating to cell sources, bioactive stimuli and scaffold or scaffold-free approaches should now contribute to progress in therapeutic development. Engineering for an inflammatory environment is required because of the need for implants to withstand immune challenge within joints affected by osteoarthritis or rheumatoid arthritis. Bringing additional cartilage repair products to the market will require an understanding of the translational vector for their commercialization. Advances thus far can facilitate the future translation of engineered cartilage products to benefit the millions of patients who suffer from cartilage injuries and arthritides. In this Review, the current landscape of tissue engineering for repair of articular cartilage is discussed, with reference to advances in cell sources, bioactive stimuli and the use of scaffolds, and with consideration of the challenges that result from the inflammatory articular environments in osteoarthritis and rheumatoid arthritis.
{"title":"Recent advancements in cartilage tissue engineering innovation and translation","authors":"Rachel C. Nordberg, Benjamin J. Bielajew, Takumi Takahashi, Shuyan Dai, Jerry C. Hu, Kyriacos A. Athanasiou","doi":"10.1038/s41584-024-01118-4","DOIUrl":"10.1038/s41584-024-01118-4","url":null,"abstract":"Articular cartilage was expected to be one of the first successfully engineered tissues, but today, cartilage repair products are few and they exhibit considerable limitations. For example, of the cell-based products that are available globally, only one is marketed for non-knee indications, none are indicated for severe osteoarthritis or rheumatoid arthritis, and only one is approved for marketing in the USA. However, advances in cartilage tissue engineering might now finally lead to the development of new cartilage repair products. To understand the potential in this field, it helps to consider the current landscape of tissue-engineered products for articular cartilage repair and particularly cell-based therapies. Advances relating to cell sources, bioactive stimuli and scaffold or scaffold-free approaches should now contribute to progress in therapeutic development. Engineering for an inflammatory environment is required because of the need for implants to withstand immune challenge within joints affected by osteoarthritis or rheumatoid arthritis. Bringing additional cartilage repair products to the market will require an understanding of the translational vector for their commercialization. Advances thus far can facilitate the future translation of engineered cartilage products to benefit the millions of patients who suffer from cartilage injuries and arthritides. In this Review, the current landscape of tissue engineering for repair of articular cartilage is discussed, with reference to advances in cell sources, bioactive stimuli and the use of scaffolds, and with consideration of the challenges that result from the inflammatory articular environments in osteoarthritis and rheumatoid arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 6","pages":"323-346"},"PeriodicalIF":33.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-07DOI: 10.1038/s41584-024-01122-8
Sarah Onuora
Drugs used to treat osteoporosis could slow the progression of osteoarthritis, according to the findings of a study in mice.
一项小鼠研究发现，用于治疗骨质疏松症的药物可以减缓骨关节炎的进展。
{"title":"Bone-modifying drugs slow OA progression","authors":"Sarah Onuora","doi":"10.1038/s41584-024-01122-8","DOIUrl":"10.1038/s41584-024-01122-8","url":null,"abstract":"Drugs used to treat osteoporosis could slow the progression of osteoarthritis, according to the findings of a study in mice.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 6","pages":"319-319"},"PeriodicalIF":33.7,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1038/s41584-024-01110-y
Jason S. Knight, Doruk Erkan
Antiphospholipid syndrome (APS) consists of thrombotic, non-thrombotic and obstetric clinical manifestations developing in individuals with persistent antiphospholipid antibodies (aPL). Although researchers have made progress in characterizing different clinical phenotypes of aPL-positive people, the current approach to clinical management is still mostly based on a ‘one size fits all’ strategy, which is derived from the results of a limited number of prospective, controlled studies. With the 2023 publication of the ACR–EULAR APS classification criteria, it is now possible to rethink APS, to lay the groundwork for subphenotyping through novel pathophysiology-informed approaches, and to set a future APS research agenda guided by unmet needs in clinical management. In this Review, Knight and Erkan consider how the 2023 ACR–EULAR classification criteria for antiphospholipid syndrome (APS) can guide future research to subphenotype APS by understanding its pathophysiology, paving the way for the personalized and proactive management of individuals with APS.
{"title":"Rethinking antiphospholipid syndrome to guide future management and research","authors":"Jason S. Knight, Doruk Erkan","doi":"10.1038/s41584-024-01110-y","DOIUrl":"10.1038/s41584-024-01110-y","url":null,"abstract":"Antiphospholipid syndrome (APS) consists of thrombotic, non-thrombotic and obstetric clinical manifestations developing in individuals with persistent antiphospholipid antibodies (aPL). Although researchers have made progress in characterizing different clinical phenotypes of aPL-positive people, the current approach to clinical management is still mostly based on a ‘one size fits all’ strategy, which is derived from the results of a limited number of prospective, controlled studies. With the 2023 publication of the ACR–EULAR APS classification criteria, it is now possible to rethink APS, to lay the groundwork for subphenotyping through novel pathophysiology-informed approaches, and to set a future APS research agenda guided by unmet needs in clinical management. In this Review, Knight and Erkan consider how the 2023 ACR–EULAR classification criteria for antiphospholipid syndrome (APS) can guide future research to subphenotype APS by understanding its pathophysiology, paving the way for the personalized and proactive management of individuals with APS.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 6","pages":"377-388"},"PeriodicalIF":33.7,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1038/s41584-024-01121-9
Robert Phillips
The peptide hormone adropin, which is downregulated in dermal fibroblasts in patients with systemic sclerosis (SSc), inhibits TGFβ-mediated fibrosis in in vitro and ex vivo models of human skin, and has potential for the treatment of SSc.
{"title":"Adropin inhibits fibrosis in SSc","authors":"Robert Phillips","doi":"10.1038/s41584-024-01121-9","DOIUrl":"10.1038/s41584-024-01121-9","url":null,"abstract":"The peptide hormone adropin, which is downregulated in dermal fibroblasts in patients with systemic sclerosis (SSc), inhibits TGFβ-mediated fibrosis in in vitro and ex vivo models of human skin, and has potential for the treatment of SSc.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 6","pages":"319-319"},"PeriodicalIF":33.7,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-02DOI: 10.1038/s41584-024-01113-9
Philippe Mertz, Nathalie Costedoat-Chalumeau, Marcela A. Ferrada, Guillaume Moulis, Arsène Mekinian, Peter C. Grayson, Laurent Arnaud
Relapsing polychondritis is a rare inflammatory disease characterized by recurrent inflammation of cartilaginous structures, mainly of the ears, nose and respiratory tract, with a broad spectrum of accompanying systemic features. Despite its rarity, prompt recognition and accurate diagnosis of relapsing polychondritis is crucial for appropriate management and optimal outcomes. Our understanding of relapsing polychondritis has changed markedly in the past couple of years with the identification of three distinct patient clusters that have different clinical manifestations and prognostic outcomes. With the progress of pangenomic sequencing and the discovery of new somatic and monogenic autoinflammatory diseases, new differential diagnoses have emerged, notably the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, autoinflammatory diseases and immune checkpoint inhibitor-related adverse events. In this Review, we present a detailed update of the newly identified clusters and highlight red flags that should raise suspicion of these alternative diagnoses. The identification of these different clusters and mimickers has a direct impact on the management, follow-up and prognosis of patients with relapsing polychondritis and autoinflammatory syndromes. Relapsing polychondritis, a rare inflammatory disorder that affects cartilaginous structures, presents challenges in diagnosis owing to overlapping symptoms with other conditions. This Review provides a clinical update on relapsing polychondritis, emphasizing the importance of distinguishing this disease from similar conditions.
{"title":"Relapsing polychondritis: clinical updates and new differential diagnoses","authors":"Philippe Mertz, Nathalie Costedoat-Chalumeau, Marcela A. Ferrada, Guillaume Moulis, Arsène Mekinian, Peter C. Grayson, Laurent Arnaud","doi":"10.1038/s41584-024-01113-9","DOIUrl":"10.1038/s41584-024-01113-9","url":null,"abstract":"Relapsing polychondritis is a rare inflammatory disease characterized by recurrent inflammation of cartilaginous structures, mainly of the ears, nose and respiratory tract, with a broad spectrum of accompanying systemic features. Despite its rarity, prompt recognition and accurate diagnosis of relapsing polychondritis is crucial for appropriate management and optimal outcomes. Our understanding of relapsing polychondritis has changed markedly in the past couple of years with the identification of three distinct patient clusters that have different clinical manifestations and prognostic outcomes. With the progress of pangenomic sequencing and the discovery of new somatic and monogenic autoinflammatory diseases, new differential diagnoses have emerged, notably the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, autoinflammatory diseases and immune checkpoint inhibitor-related adverse events. In this Review, we present a detailed update of the newly identified clusters and highlight red flags that should raise suspicion of these alternative diagnoses. The identification of these different clusters and mimickers has a direct impact on the management, follow-up and prognosis of patients with relapsing polychondritis and autoinflammatory syndromes. Relapsing polychondritis, a rare inflammatory disorder that affects cartilaginous structures, presents challenges in diagnosis owing to overlapping symptoms with other conditions. This Review provides a clinical update on relapsing polychondritis, emphasizing the importance of distinguishing this disease from similar conditions.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 6","pages":"347-360"},"PeriodicalIF":33.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140819419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30DOI: 10.1038/s41584-024-01109-5
Alexandre Aubert, Karen Jung, Sho Hiroyasu, Julian Pardo, David J. Granville
Granzymes (granule-secreted enzymes) are a family of serine proteases that have been viewed as redundant cytotoxic enzymes since their discovery more than 30 years ago. Predominantly produced by cytotoxic lymphocytes and natural killer cells, granzymes are delivered into the cytoplasm of target cells through immunological synapses in cooperation with the pore-forming protein perforin. After internalization, granzymes can initiate cell death through the cleavage of intracellular substrates. However, evidence now also demonstrates the existence of non-cytotoxic, pro-inflammatory, intracellular and extracellular functions that are granzyme specific. Under pathological conditions, granzymes can be produced and secreted extracellularly by immune cells as well as by non-immune cells. Depending on the granzyme, accumulation in the extracellular milieu might contribute to inflammation, tissue injury, impaired wound healing, barrier dysfunction, osteoclastogenesis and/or autoantigen generation. Granzyme serine proteases are known for their perforin-dependent cytotoxic activities, but evidence also indicates that they have a range of non-cytotoxic, pro-inflammatory intracellular and extracellular functions. In this Review, the authors discuss granzyme biology with an emphasis on its involvement in rheumatic disease pathology.
{"title":"Granzyme serine proteases in inflammation and rheumatic diseases","authors":"Alexandre Aubert, Karen Jung, Sho Hiroyasu, Julian Pardo, David J. Granville","doi":"10.1038/s41584-024-01109-5","DOIUrl":"10.1038/s41584-024-01109-5","url":null,"abstract":"Granzymes (granule-secreted enzymes) are a family of serine proteases that have been viewed as redundant cytotoxic enzymes since their discovery more than 30 years ago. Predominantly produced by cytotoxic lymphocytes and natural killer cells, granzymes are delivered into the cytoplasm of target cells through immunological synapses in cooperation with the pore-forming protein perforin. After internalization, granzymes can initiate cell death through the cleavage of intracellular substrates. However, evidence now also demonstrates the existence of non-cytotoxic, pro-inflammatory, intracellular and extracellular functions that are granzyme specific. Under pathological conditions, granzymes can be produced and secreted extracellularly by immune cells as well as by non-immune cells. Depending on the granzyme, accumulation in the extracellular milieu might contribute to inflammation, tissue injury, impaired wound healing, barrier dysfunction, osteoclastogenesis and/or autoantigen generation. Granzyme serine proteases are known for their perforin-dependent cytotoxic activities, but evidence also indicates that they have a range of non-cytotoxic, pro-inflammatory intracellular and extracellular functions. In this Review, the authors discuss granzyme biology with an emphasis on its involvement in rheumatic disease pathology.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 6","pages":"361-376"},"PeriodicalIF":33.7,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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