Pub Date : 2024-01-05DOI: 10.1016/j.autrev.2024.103515
Prashant Giri , Dharm Desai , Mitesh Dwivedi
Vitiligo is a chronic skin condition marked by the gradual loss of pigmentation, leading to the emergence of white or depigmented patches on the skin. The exact cause of vitiligo remains not entirely understood, although it is thought to involve a blend of genetic, autoimmune, and environmental factors. While there is currently no definitive cure for vitiligo, diverse treatments exist that may assist in managing the condition and fostering repigmentation in specific instances. Animal models play a pivotal role in comprehending the intricate mechanisms that underlie vitiligo, providing valuable insights into the progression and onset of the disease, as well as potential therapeutic interventions. Although induced experimental models lack the nuanced characteristics observed in natural experimental models, relying solely on a single animal model might not fully capture the intricate pathogenesis of vitiligo. Different animal models simulate specific aspects of human vitiligo pathogenesis to varying degrees. This review extensively explores the array of animal models utilized in vitiligo research, shedding light on their respective advantages, disadvantages, and applications.
{"title":"Animal models unraveling the complexity of vitiligo pathogenesis","authors":"Prashant Giri , Dharm Desai , Mitesh Dwivedi","doi":"10.1016/j.autrev.2024.103515","DOIUrl":"10.1016/j.autrev.2024.103515","url":null,"abstract":"<div><p>Vitiligo<span> is a chronic skin condition marked by the gradual loss of pigmentation<span>, leading to the emergence of white or depigmented patches on the skin. The exact cause of vitiligo remains not entirely understood, although it is thought to involve a blend of genetic, autoimmune, and environmental factors<span>. While there is currently no definitive cure for vitiligo, diverse treatments exist that may assist in managing the condition and fostering repigmentation in specific instances. Animal models play a pivotal role in comprehending the intricate mechanisms that underlie vitiligo, providing valuable insights into the progression and onset of the disease, as well as potential therapeutic interventions. Although induced experimental models lack the nuanced characteristics observed in natural experimental models, relying solely on a single animal model might not fully capture the intricate pathogenesis of vitiligo. Different animal models simulate specific aspects of human vitiligo pathogenesis to varying degrees. This review extensively explores the array of animal models utilized in vitiligo research, shedding light on their respective advantages, disadvantages, and applications.</span></span></span></p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101896","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}
Pre-capillary pulmonary arterial hypertension (PAH) is hemodynamically characterized by a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg, pulmonary capillary wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) > 2. PAH is classified in six clinical subgroups, including idiopathic PAH (IPAH) and PAH associated to connective tissue diseases (CTD-PAH), that will be the main object of this review. The aim is to compare these two PAH subgroups in terms of epidemiology, histological and pathogenic findings in an attempt to define disease-specific features, including autoimmunity, that may explain the heterogeneity of response to therapy between IPAH and CTD-PAH.
{"title":"Idiopathic and connective tissue disease-associated pulmonary arterial hypertension (PAH): Similarities, differences and the role of autoimmunity","authors":"Elvira Favoino , Marcella Prete , Vasiliki Liakouli , Patrizia Leone , Adriana Sisto , Luca Navarini , Marta Vomero , Francesco Ciccia , Piero Ruscitti , Vito Racanelli , Roberto Giacomelli , Federico Perosa","doi":"10.1016/j.autrev.2024.103514","DOIUrl":"10.1016/j.autrev.2024.103514","url":null,"abstract":"<div><p>Pre-capillary pulmonary arterial hypertension (PAH) is hemodynamically characterized by a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg, pulmonary capillary wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) > 2. PAH is classified in six clinical subgroups, including idiopathic PAH (IPAH) and PAH associated to connective tissue diseases (CTD-PAH), that will be the main object of this review. The aim is to compare these two PAH subgroups in terms of epidemiology, histological and pathogenic findings in an attempt to define disease-specific features, including autoimmunity, that may explain the heterogeneity of response to therapy between IPAH and CTD-PAH.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997224000016/pdfft?md5=b45530e4db6093408732dabfda63db8d&pid=1-s2.0-S1568997224000016-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139095158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sjӧgren's disease (SjD) is a systemic autoimmune disorder characterized by the chronic inflammation and dysfunction of exocrine glands, mainly salivary glands, causing dryness of the eyes and of the mouth. The disease may affect different organs and tissues with complex and heterogeneous clinical presentation, usually with sicca symptoms, profound fatigue, chronic pain, major organ involvement, and lymphomas. SjD diagnosis is based on the combination of clinical, serological, and functional tests with histological biomarkers. Minor salivary gland biopsy (mSGB) represents the cornerstone for the diagnosis of SjD, allowing the study of the characteristic focal infiltration of B- and T lymphocytes. Besides, mSGB might also have a prognostic role, being the infiltrates more complex in patients with severe SjD. But biopsy, so far, is not mandatory for SjD and mSG ultrasound and peripheral biomarkers might replace its role in the future. Another important aspect of SjD is the presence of autoantibodies, although 20 to 30% of patients are “seronegative” for specific autoantibodies (ANA, antiRo/SSA, antiLa/SSB). The characteristics of this subset of patients are currently under evaluation and “new” autoantibodies and biomarkers might be necessary for better patient's stratification and follow-up.
{"title":"Is minor salivary gland biopsy still mandatory in Sjogren's syndrome? Does seronegative Sjogren's syndrome exist?","authors":"Chiara Baldini , Onorina Berardicurti , Roberto Giacomelli , Michele Bombardieri","doi":"10.1016/j.autrev.2023.103425","DOIUrl":"10.1016/j.autrev.2023.103425","url":null,"abstract":"<div><p><span><span>Sjӧgren's disease (SjD) is a systemic autoimmune disorder characterized by the chronic inflammation and dysfunction of </span>exocrine glands, mainly </span>salivary glands<span><span>, causing dryness of the eyes and of the mouth. The disease may affect different organs and tissues with complex and heterogeneous clinical presentation, usually with sicca </span>symptoms<span><span><span>, profound fatigue, chronic pain, major organ involvement, and lymphomas. SjD diagnosis is based on the combination of clinical, serological, and functional tests with histological biomarkers. Minor salivary gland biopsy (mSGB) represents the cornerstone for the diagnosis of SjD, allowing the study of the characteristic focal infiltration of B- and </span>T lymphocytes. Besides, mSGB might also have a prognostic role, being the infiltrates more complex </span>in patients with severe SjD. But biopsy, so far, is not mandatory for SjD and mSG ultrasound and peripheral biomarkers might replace its role in the future. Another important aspect of SjD is the presence of autoantibodies, although 20 to 30% of patients are “seronegative” for specific autoantibodies (ANA, antiRo/SSA, antiLa/SSB). The characteristics of this subset of patients are currently under evaluation and “new” autoantibodies and biomarkers might be necessary for better patient's stratification and follow-up.</span></span></p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10074480","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 : 2024-01-01DOI: 10.1016/j.autrev.2023.103424
Daniel Clauw , Piercarlo Sarzi-Puttini , Greta Pellegrino , Yehuda Shoenfeld
Fibromyalgia (FM) is a multifactorial syndrome which includes not only widespread pain and stiffness, now recognized as major symptoms, but also numerous other somatic, emotional, and neuropsychic manifestation. The lack of specific validated biological and instrumental biomarkers has made FM a condition of unexplained medical significance, and its pathophysiology remains controversial and subject to debate. The current hypothesis regarding the pathogenesis of FM proposes that its development is influenced by various mechanism, including genetic predisposition, stressful life events, inflammatory processes, and cognitive-emotional factors. However, despite the extensive research conducted to date, the available data do not provide a clear understanding of the pathogenesis of FM.
In this article, we report the opposing viewpoints of two leading experts who debate the question of whether FM is an autoimmune disease, based on scientific data regarding this condition. Both perspectives are discussed and the latest evidence on the pathophysiology of FM is reported to provide a comprehensive understanding of this complex syndrome.
{"title":"Is fibromyalgia an autoimmune disorder?","authors":"Daniel Clauw , Piercarlo Sarzi-Puttini , Greta Pellegrino , Yehuda Shoenfeld","doi":"10.1016/j.autrev.2023.103424","DOIUrl":"10.1016/j.autrev.2023.103424","url":null,"abstract":"<div><p>Fibromyalgia (FM) is a multifactorial syndrome which includes not only widespread pain and stiffness, now recognized as major symptoms, but also numerous other somatic, emotional, and neuropsychic manifestation. The lack of specific validated biological and instrumental biomarkers has made FM a condition of unexplained medical significance, and its pathophysiology remains controversial and subject to debate. The current hypothesis regarding the pathogenesis of FM proposes that its development is influenced by various mechanism, including genetic predisposition, stressful life events, inflammatory processes, and cognitive-emotional factors. However, despite the extensive research conducted to date, the available data do not provide a clear understanding of the pathogenesis of FM.</p><p>In this article, we report the opposing viewpoints of two leading experts who debate the question of whether FM is an autoimmune disease, based on scientific data regarding this condition. Both perspectives are discussed and the latest evidence on the pathophysiology of FM is reported to provide a comprehensive understanding of this complex syndrome.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997223001581/pdfft?md5=6a7df06b2b378680d293b512992ec8da&pid=1-s2.0-S1568997223001581-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10074483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glucocorticoids (GCs) remain a cornerstone of the treatment of Systemic Lupus Erythematosus (SLE). Numerous studies have emphasized the risk of damage accrual in SLE patient treated with GC, but currently, it is not possible to dissociate favorable and undesirable effects of GCs because their underlying mechanisms are entangled at the molecular level. Here, we review whether available data suggest that it is possible, feasible and desirable to taper and discontinue GC treatment in SLE. The main potential concern with GC withdrawal is the risk of SLE flare, which is strongly associated with increased organ damage, mortality, healthcare costs, decreased quality of life and work productivity. While most studies have assumed the cut off point for low doses (e.g. 7.5/mg/d) as the limit for safety, it is still controversial whether lower doses may influence damage accrual long-term. Also, a recent randomized trial has shown that a daily dose of 5 mg of prednisone in SLE patients in short-term remission can prevent up to 50–75% of flares, with an acceptable safety profile. However, this treatment is not mandatory for all patients. Yet, several observational studies highlight that discontinuation of GC is associated with lower damage accrual. Currently, we do not have a reliable method to identify patients who may require long-term low-dose GC. Therefore, further research is needed to identify a subgroup at high risk of relapse who would benefit from continuing prednisone. In the meantime, when considering the discontinuation of very low-dose prednisone, the decision must be individualized, as HCQ and conventional immunosuppressive agents are not without risk of side effects.
{"title":"Is it safe to withdraw low-dose glucocorticoids in SLE patients in remission?","authors":"Alexis Mathian , Laurent Arnaud , Guillermo Ruiz-Irastorza","doi":"10.1016/j.autrev.2023.103446","DOIUrl":"10.1016/j.autrev.2023.103446","url":null,"abstract":"<div><p><span>Glucocorticoids<span><span> (GCs) remain a cornerstone of the treatment of </span>Systemic Lupus Erythematosus (SLE). Numerous studies have emphasized the risk of damage accrual in SLE patient treated with GC, but currently, it is not possible to dissociate favorable and undesirable effects of GCs because their underlying mechanisms are entangled at the molecular level. Here, we review whether available data suggest that it is possible, feasible and desirable to taper and discontinue GC treatment in SLE. The main potential concern with GC withdrawal is the risk of SLE flare, which is strongly associated with increased organ damage, mortality, healthcare costs, decreased </span></span>quality of life<span> and work productivity. While most studies have assumed the cut off point for low doses<span><span> (e.g. 7.5/mg/d) as the limit for safety, it is still controversial whether lower doses may influence damage accrual long-term. Also, a recent randomized trial has shown that a daily dose of 5 mg of prednisone<span> in SLE patients in short-term remission can prevent up to 50–75% of flares, with an acceptable safety profile. However, this treatment is not mandatory for all patients. Yet, several observational studies highlight that discontinuation of GC is associated with lower damage accrual. Currently, we do not have a reliable method to identify patients who may require long-term low-dose GC. Therefore, further research is needed to identify a subgroup at high risk of relapse who would benefit from continuing prednisone. In the meantime, when considering the discontinuation of very low-dose prednisone, the decision must be individualized, as </span></span>HCQ<span> and conventional immunosuppressive agents are not without risk of side effects.</span></span></span></p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10208585","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 : 2024-01-01DOI: 10.1016/j.autrev.2023.103439
Corrado Campochiaro , Yannick Allanore , Yolanda Braun-Moscovici , Marco Matucci-Cerinic , Alexandra Balbir-Gurman
Cyclophosphamide (CYC) has been a gold standard of treatment for severe progressive Systemic Sclerosis (SSc), especially in patients with concomitant interstitial lung disease (ILD). This approach was based on results of several interventional studies, including randomized control trials, which mainly addressed SSc-ILD as a primary end point and skin involvement as a second one. The use of CYC is time-limited due to significant adverse events. More recently, other immunosuppressive and biological agents showed efficacy but better safety profile in patients with SSc and SSc-ILD. With regards to other end-points, post-hoc analyses, systematic reviews and metalysis showed that CYC had limited influence on patients' quality of life, event-free survival and mortality. Comprehensive patient's stratification according to a molecular, cellular and phenotypic pattern may help in choosing of personalized medicine with more ambitious treatment effect and should be the future direction. According to the above available data and even if scientific evidence may be missing, experts' opinion has changed the attitude to CYC as an anchor drug in the management of severe SSc. Indeed, CYC has been pushed to the second and even third treatment option after mycophenolate mofetil, tocilizumab or rituximab. This position became obvious during debate on this topic at CORA meeting 2023.
{"title":"Is cyclophosphamide still the gold standard in early severe rapidly progressive systemic sclerosis?","authors":"Corrado Campochiaro , Yannick Allanore , Yolanda Braun-Moscovici , Marco Matucci-Cerinic , Alexandra Balbir-Gurman","doi":"10.1016/j.autrev.2023.103439","DOIUrl":"10.1016/j.autrev.2023.103439","url":null,"abstract":"<div><p><span><span><span><span><span>Cyclophosphamide<span> (CYC) has been a gold standard of treatment for severe </span></span>progressive Systemic Sclerosis (SSc), especially </span>in patients<span> with concomitant interstitial lung disease (ILD). This approach was based on results of several interventional studies, including </span></span>randomized control trials, which mainly addressed SSc-ILD as a primary end point and skin involvement as a second one. The use of CYC is time-limited due to significant adverse events. More recently, other immunosuppressive and biological agents showed efficacy but better safety profile in patients with SSc and SSc-ILD. With regards to other end-points, post-hoc analyses, </span>systematic reviews<span> and metalysis<span> showed that CYC had limited influence on patients' quality of life, event-free survival and mortality. Comprehensive patient's stratification according to a molecular, cellular and phenotypic pattern may help in choosing of personalized medicine with more ambitious treatment effect and should be the future direction. According to the above available data and even if scientific evidence may be missing, experts' opinion has changed the attitude to CYC as an anchor drug in the management of severe SSc. Indeed, CYC has been pushed to the second and even third treatment option after </span></span></span>mycophenolate mofetil<span>, tocilizumab<span><span> or rituximab. This </span>position became obvious during debate on this topic at CORA meeting 2023.</span></span></p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10608341","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 : 2024-01-01DOI: 10.1016/j.autrev.2023.103415
Carlo Salvarani , Roberto Padoan , Luca Iorio , Alessandro Tomelleri , Benjamin Terrier , Francesco Muratore , Bhaskar Dasgupta
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common conditions in older adults. Their clinical connection has been recognized over time, with many patients experiencing both conditions separately, simultaneously or in temporal sequence to each other. Early GCA detection is essential to prevent vascular damage, but identifying subclinical GCA in PMR patients remains a challenge and routine screening is not standard practice. Subclinical GCA prevalence in newly diagnosed PMR patients ranges from 23 to 29%, depending on the screening method. Vessel wall imaging and temporal artery biopsy can detect subclinical GCA. Epidemiology and trigger factors show similarities between the two conditions, but PMR is more common than GCA. Genetic and pathogenesis studies reveal shared inflammatory mechanisms involving dendritic cells, pro-inflammatory macrophages, and an IL-6 signature. However, the inflammatory infiltrates differ, with extensive T cell infiltrates seen in GCA while PMR shows an incomplete profile of T cell and macrophage-derived cytokines. Glucocorticoid treatment is effective for both conditions, but the steroid requirements vary. PMR overall mortality might be similar to the general population, while GCA patients with aortic inflammatory aneurysms face increased mortality risk. The GCA-PMR association warrants further research. Considering their kinship, recently the term GCA-PMR Spectrum Disease (GPSD) has been proposed.
{"title":"Subclinical giant cell arteritis in polymyalgia rheumatica: Concurrent conditions or a common spectrum of inflammatory diseases?","authors":"Carlo Salvarani , Roberto Padoan , Luca Iorio , Alessandro Tomelleri , Benjamin Terrier , Francesco Muratore , Bhaskar Dasgupta","doi":"10.1016/j.autrev.2023.103415","DOIUrl":"10.1016/j.autrev.2023.103415","url":null,"abstract":"<div><p>Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common conditions in older adults. Their clinical connection has been recognized over time, with many patients experiencing both conditions separately, simultaneously or in temporal sequence to each other. Early GCA detection is essential to prevent vascular damage, but identifying subclinical GCA in PMR patients remains a challenge and routine screening is not standard practice. Subclinical GCA prevalence in newly diagnosed PMR patients ranges from 23 to 29%, depending on the screening method. Vessel wall imaging and temporal artery biopsy can detect subclinical GCA. Epidemiology and trigger factors show similarities between the two conditions, but PMR is more common than GCA. Genetic and pathogenesis studies reveal shared inflammatory mechanisms involving dendritic cells, pro-inflammatory macrophages, and an IL-6 signature. However, the inflammatory infiltrates differ, with extensive T cell infiltrates seen in GCA while PMR shows an incomplete profile of T cell and macrophage-derived cytokines. Glucocorticoid treatment is effective for both conditions, but the steroid requirements vary. PMR overall mortality might be similar to the general population, while GCA patients with aortic inflammatory aneurysms face increased mortality risk. The GCA-PMR association warrants further research. Considering their kinship, recently the term GCA-PMR Spectrum Disease (GPSD) has been proposed.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997223001490/pdfft?md5=fd56a0c92561b5982cce4adea90f1b21&pid=1-s2.0-S1568997223001490-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.autrev.2023.103510
Cecilia B. Chighizola , Rohan Willis , Gabriella Maioli , Savino Sciascia , Laura Andreoli , Olga Amengual , Massimo Radin , Maria Gerosa , Tatsuya Atsumi , Guilherme de Jesus , Laura Trespidi , D. Ware Branch , Roberto Caporali , Danieli Andrade , Robert Roubey , Michelle Petri , Maria Laura Bertolaccini
In antiphospholipid syndrome (APS), the risk of clinical manifestations increases with higher titers of antiphospholipid antibodies (aPL). Despite the adoption of aPL titers in the classification approach to aPL-positive subjects, the value of longitudinal monitoring of those titers in the follow-up is still debated, being well studied only in systemic lupus erythematosus (SLE). The literature suggests that the rate of aPL positivity decreases during follow-up in primary APS, estimating that seroconversion occurs in between 8.9 and 59% of patients over time. Negativisation of aPL occurs more frequently in asymptomatic aPL carriers than in patients with full-blown APS as well as in subjects with single aPL positivity or low aPL antibody titers. In patients with SLE, aPL typically behave fluctuating from positive to negative and back again in the course of follow-up.
The few studies assessing the longitudinal course of aPL positivity with no associated systemic connective tissue disease reported a progressive decrement of aPL titers over time, in particular of antibodies against β2 glycoprotein I (antiβ2GPI) and cardiolipin (aCL) of IgG isotype. After a thrombotic event, aPL titers tend to decrease, as emerged from cohorts of both primary and secondary APS. Hydroxychloroquine has been identified as the most effective pharmacological agent to reduce aPL titers, with multiple studies demonstrating a parallel reduction in thrombosis rate. This review addresses available evidence on the significance of aPL titer fluctuation from clinical, therapeutic and pathogenic perspectives.
{"title":"Deciphering the clinical significance of longitudinal antiphospholipid antibody titers","authors":"Cecilia B. Chighizola , Rohan Willis , Gabriella Maioli , Savino Sciascia , Laura Andreoli , Olga Amengual , Massimo Radin , Maria Gerosa , Tatsuya Atsumi , Guilherme de Jesus , Laura Trespidi , D. Ware Branch , Roberto Caporali , Danieli Andrade , Robert Roubey , Michelle Petri , Maria Laura Bertolaccini","doi":"10.1016/j.autrev.2023.103510","DOIUrl":"10.1016/j.autrev.2023.103510","url":null,"abstract":"<div><p><span>In antiphospholipid syndrome<span><span> (APS), the risk of clinical manifestations increases with higher titers of antiphospholipid antibodies<span> (aPL). Despite the adoption of aPL titers in the classification approach to aPL-positive subjects, the value of longitudinal monitoring of those titers in the follow-up is still debated, being well studied only in systemic lupus erythematosus (SLE). The literature suggests that the rate of aPL positivity decreases during follow-up in primary APS, estimating that </span></span>seroconversion occurs in between 8.9 and 59% of patients over time. Negativisation of aPL occurs more frequently in asymptomatic aPL carriers than </span></span>in patients<span> with full-blown APS as well as in subjects with single aPL positivity or low aPL antibody titers. In patients with SLE, aPL typically behave fluctuating from positive to negative and back again in the course of follow-up.</span></p><p><span>The few studies assessing the longitudinal course of aPL positivity with no associated systemic connective tissue disease<span> reported a progressive decrement of aPL titers over time, in particular of antibodies against β2 glycoprotein I (antiβ2GPI) and </span></span>cardiolipin<span> (aCL) of IgG isotype<span>. After a thrombotic event, aPL titers tend to decrease, as emerged from cohorts of both primary and secondary APS. Hydroxychloroquine has been identified as the most effective pharmacological agent to reduce aPL titers, with multiple studies demonstrating a parallel reduction in thrombosis rate. This review addresses available evidence on the significance of aPL titer fluctuation from clinical, therapeutic and pathogenic perspectives.</span></span></p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139061797","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 : 2024-01-01DOI: 10.1016/j.autrev.2023.103418
Ioannis Parodis , Roberto Depascale , Andrea Doria , Hans-Joachim Anders
Although the prognosis of lupus nephritis (LN) has improved over the last few decades, 5–20% of patients still progress to kidney failure. Hence, there is an unmet need to improve the management of LN. Two novel drugs, belimumab and voclosporin, have been recently approved for LN and obinutuzumab is in the late stage of development. In randomised controlled trials (RCTs), all these drugs, added to the standard-of-care, were more effective than standard-of-care alone in achieving renal response. Now the question is: should these new drugs be used early in the disease course or just in refractory patients? The main reasons supporting the early use are based on the RCTs that demonstrated benefits when combinatory regimen was initiated early in incident and relapsing patients leading to a higher proportion of patients to achieve renal response, hence reducing nephron loss and the risk of kidney failure. The main reasons supporting the use of the combinatory regimens primarily in relapsing/refractory patients acknowledge that many patients responded well even without add-on medications, allowing a more economic use of innovative and costly drugs. However, good predictors of renal response to standard-of-care are lacking and, thus, the decision of adding new treatments early or just in refractory or relapsing patients has to consider drug access, risks of over or undertreatment, and preservation of kidney function in high-risk individuals.
{"title":"When should targeted therapies be used in the treatment of lupus nephritis: Early in the disease course or in refractory patients?","authors":"Ioannis Parodis , Roberto Depascale , Andrea Doria , Hans-Joachim Anders","doi":"10.1016/j.autrev.2023.103418","DOIUrl":"10.1016/j.autrev.2023.103418","url":null,"abstract":"<div><p>Although the prognosis of lupus nephritis (LN) has improved over the last few decades, 5–20% of patients still progress to kidney failure. Hence, there is an unmet need to improve the management of LN. Two novel drugs, belimumab and voclosporin, have been recently approved for LN and obinutuzumab is in the late stage of development. In randomised controlled trials (RCTs), all these drugs, added to the standard-of-care, were more effective than standard-of-care alone in achieving renal response. Now the question is: should these new drugs be used early in the disease course or just in refractory patients? The main reasons supporting the early use are based on the RCTs that demonstrated benefits when combinatory regimen was initiated early in incident and relapsing patients leading to a higher proportion of patients to achieve renal response, hence reducing nephron loss and the risk of kidney failure. The main reasons supporting the use of the combinatory regimens primarily in relapsing/refractory patients acknowledge that many patients responded well even without add-on medications, allowing a more economic use of innovative and costly drugs. However, good predictors of renal response to standard-of-care are lacking and, thus, the decision of adding new treatments early or just in refractory or relapsing patients has to consider drug access, risks of over or undertreatment, and preservation of kidney function in high-risk individuals.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997223001520/pdfft?md5=89dcd5343f10dfd5da877d5faf192174&pid=1-s2.0-S1568997223001520-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10096127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.autrev.2023.103429
Roberto Caporali , Sabino Germinario , Dorottya Kacsándi , Ernest Choy , Zoltán Szekanecz
Janus Kinase inhibitors (JAKi) have been approved for the treatment of Rheumatoid Arthritis (RA) for several years. They are the first oral advanced treatment with efficacy similar to, if not greater than, biologic agents. Recently, concerns over their safety was raised by the results from Oral Surveillance trial suggesting that tofacitinib, one of the JAKi, was associated with higher cardiovascular adverse events and malignancies than TNF inhibitors (TNFi). Since then, regulatory authorities have added warnings to the labels of JAKi. On this purpose, whether rheumatologists should use JAKi as first line advance treatment has become a controversial topic. Some rheumatologists have argued that biologics should be first line advance treatment since there are extensive effectiveness and safety data. In addition, with the advent of biosimilar drugs, they are the most cost-effective treatment. On the other hand, JAKi are very efficacious and are generally safe apart from older and high-risk patients. When TNFi are contraindicated and in certain RA patients ,especially when an oral drug is preferable, JAKi have significant advantage providing patients are involved in the decision-making process.
Janus 激酶抑制剂(JAKi)获准用于治疗类风湿性关节炎(RA)已有数年。它们是第一种口服高级治疗药物,疗效与生物制剂相似,甚至更强。最近,口服监测试验结果表明,与 TNF 抑制剂(TNFi)相比,JAKi 药物之一托法替尼与更高的心血管不良事件和恶性肿瘤相关,这引起了人们对其安全性的担忧。此后,监管机构在JAKi的标签上增加了警告字样。为此,风湿病学家是否应将 JAKi 作为一线先期治疗药物已成为一个有争议的话题。一些风湿病学家认为,生物制剂应作为一线先期治疗药物,因为已有大量的有效性和安全性数据。此外,随着生物类似药的出现,它们是最具成本效益的治疗方法。另一方面,JAKi疗效显著,除了老年患者和高危患者外,一般都是安全的。在TNFi禁忌症和某些RA患者中,尤其是在口服药物更可取的情况下,只要患者参与决策过程,JAKi就有明显的优势。
{"title":"Start RA treatment – Biologics or JAK-inhibitors?","authors":"Roberto Caporali , Sabino Germinario , Dorottya Kacsándi , Ernest Choy , Zoltán Szekanecz","doi":"10.1016/j.autrev.2023.103429","DOIUrl":"10.1016/j.autrev.2023.103429","url":null,"abstract":"<div><p><span>Janus Kinase inhibitors<span><span><span> (JAKi) have been approved for the treatment of </span>Rheumatoid Arthritis (RA) for several years. They are the first oral advanced treatment with efficacy similar to, if not greater than, biologic agents. Recently, concerns over their safety was raised by the results from Oral Surveillance trial suggesting that </span>tofacitinib, one of the JAKi, was associated with higher cardiovascular adverse events and </span></span>malignancies<span><span> than TNF inhibitors (TNFi). Since then, regulatory authorities have added warnings to the labels of JAKi. On this purpose, whether rheumatologists should use JAKi as first line advance treatment has become a controversial topic. Some rheumatologists have argued that biologics should be first line advance treatment since there are extensive effectiveness and safety data. In addition, with the advent of </span>biosimilar drugs, they are the most cost-effective treatment. On the other hand, JAKi are very efficacious and are generally safe apart from older and high-risk patients. When TNFi are contraindicated and in certain RA patients ,especially when an oral drug is preferable, JAKi have significant advantage providing patients are involved in the decision-making process.</span></p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235101","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}