Journal of Translational Autoimmunity最新文献

{"title":"PPAR agonists for the treatment of primary biliary cholangitis: Old and new tales","authors":"Francesca Colapietro ,&nbsp;M. Eric Gershwin ,&nbsp;Ana Lleo","doi":"10.1016/j.jtauto.2023.100188","DOIUrl":"10.1016/j.jtauto.2023.100188","url":null,"abstract":"<div><h3>Introduction</h3><p>Primary biliary cholangitis (PBC) is an autoimmune liver disease involving the small intrahepatic bile ducts; when untreated or undertreated, it may evolve to liver fibrosis and cirrhosis. Ursodeoxycholic Acid (UDCA) is the standard of care treatment, Obeticholic Acid (OCA) has been approved as second-line therapy for those non responder or intolerant to UDCA. However, due to moderate rate of UDCA-non responders and to warnings recently issued against OCA use in patients with cirrhosis, further therapies are needed.</p><p><u>Areas covered.</u> Deep investigations into the pathogenesis of PBC is leading to proposal of new therapeutic agents, among which peroxisome proliferator-activated receptor (PPAR) ligands seem to be highly promising given the preliminary, positive results in Phase 2 and 3 trials. Bezafibrate, the most evaluated, is currently used in clinical practice in combination with UDCA in referral centers. We herein describe completed and ongoing trials involving PPAR agonists use in PBC, analyzing pits and falls.</p></div><div><h3>Expert opinion</h3><p>Testing new therapeutic opportunities in PBC is challenging due to its low prevalence and slow progression. However, new drugs including PPAR agonists, are currently under investigation and should be considered for at-risk PBC patients.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100188"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/6b/main.PMC9850184.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10579003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering live attenuated vaccines: Old dogs learning new tricks","authors":"Julia Plocica ,&nbsp;Fengguang Guo ,&nbsp;Jugal Kishore Das ,&nbsp;Koichi S. Kobayashi ,&nbsp;Thomas A. Ficht ,&nbsp;Robert C. Alaniz ,&nbsp;Jianxun Song ,&nbsp;Paul de Figueiredo","doi":"10.1016/j.jtauto.2023.100198","DOIUrl":"10.1016/j.jtauto.2023.100198","url":null,"abstract":"<div><p>Autoimmune diseases such as rheumatoid arthritis and type 1 diabetes are increasingly common global problems. Concerns about increases in the prevalence of such diseases and the limited efficacy of conventional treatment regimens necessitates new therapies to address these challenges. Autoimmune disease severity and dysbiosis are interconnected. Although probiotics have been established as a therapy to rebalance the microbiome and suppress autoimmune symptoms, these microbes tend to lack a number of advantageous qualities found in non-commensal bacteria. Through attenuation and genetic manipulation, these non-commensal bacteria have been engineered into recombinant forms that offer malleable platforms capable of addressing the immune imbalances found in RA and T1D. Such bacteria have been engineered to express valuable gene products known to suppress autoimmunity such as anti-inflammatory cytokines, autoantigens, and enzymes synthesizing microbial metabolites. This review will highlight current and emerging trends in the field and discuss how they may be used to prevent and control autoimmune diseases.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100198"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113845/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9741628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FRTX-02, a selective and potent inhibitor of DYRK1A, modulates inflammatory pathways in mouse models of psoriasis and atopic dermatitis","authors":"Soochan Kim ,&nbsp;Eunhwa Ko ,&nbsp;Hwan Geun Choi ,&nbsp;Daekwon Kim ,&nbsp;Monica Luchi ,&nbsp;Bernard Khor ,&nbsp;Sunghwan Kim","doi":"10.1016/j.jtauto.2022.100185","DOIUrl":"10.1016/j.jtauto.2022.100185","url":null,"abstract":"<div><p>Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) has been proposed as a novel regulator of adaptive immune homeostasis through modulating T cell polarization. Thus, DYRK1A could present a potential target in autoimmune disorders. Here, we identify FRTX-02 as a novel compound exhibiting potent and selective inhibition of DYRK1A. FRTX-02 induced transcriptional activity of the DYRK1A substrate NFAT in T cell lines. Correspondingly, FRTX-02 promoted ex vivo CD4⁺ polarization into anti-inflammatory Tregs and reduced their polarization into pro-inflammatory Th1 or Th17 cells. We show that FRTX-02 could also limit innate immune responses through negative regulation of the MyD88/IRAK4–NF-κB axis in a mast cell line. Finally, in mouse models of psoriasis and atopic dermatitis, both oral and topical formulations of FRTX-02 reduced inflammation and disease biomarkers in a dose-dependent manner. These results support further studies of DYRK1A inhibitors, including FRTX-02, as potential therapies for chronic inflammatory and autoimmune conditions.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100185"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/55/main.PMC9841288.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9114848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal mixture exposures and multiplexed autoantibody screening in Navajo communities exposed to uranium mine wastes","authors":"Esther Erdei ,&nbsp;Chris Shuey ,&nbsp;Curtis Miller ,&nbsp;Joseph Hoover ,&nbsp;Miranda Cajero ,&nbsp;Johnnye Lewis","doi":"10.1016/j.jtauto.2023.100201","DOIUrl":"10.1016/j.jtauto.2023.100201","url":null,"abstract":"<div><h3>Background</h3><p>Environmental exposures to metals in uranium mining wastes and drinking water were documented in more than half of the 1304 Navajo community members of the Diné Network for Environmental Health (DiNEH) Project, the first comprehensive assessment of exposures to these metals and community health on the Navajo Nation.</p></div><div><h3>Objective</h3><p>Evaluate environmental exposures among participants who provided blood and urine samples using multiplexed autoantibody positivity as an early effect biomarker.</p></div><div><h3>Methods</h3><p>Survey and geospatial location data, well water quality, and metals biomonitoring were used to assess exposures to mixed-metal wastes from 100 abandoned uranium waste sites.</p></div><div><h3>Results</h3><p>We observed that the prevalence of multiplexed autoantibody positivity in 239 participants was more than double that reported for the U.S. population (27.2% v. 13.8%) even though the national prevalence was generated using a different assay, the HEp-2 cell-based antinuclear antibody test. Increased risk of multiplexed autoantibody screening positivity (OR = 3.07,95%CI 1.15–8.22) was found among DiNEH study people who lived close to uranium mine and milling wastes and consumed metals in drinking water. Associations for females were even stronger when they lived closed to contaminated uranium mining and milling sites. <em>Anti</em>-U1-RNP antibodies were associated with water consumption of nickel.</p></div><div><h3>Conclusion</h3><p>Proximity to waste sites and consumption of metals in water even below current drinking water standards were associated with perturbations of immune tolerance. These findings are consistent with previous studies of autoimmunity in the local population and demonstrate that multiplexed autoantibody screening method has a potential as sentinel indicator of exposures to environmental metals.</p></div><div><h3>Impact statement</h3><p>This is the first, community-engaged environmental health study in exposed Navajo communities that applied clinical multiplexed testing in risk assessment of environmental metals associated with abandoned, unremediated uranium mining and milling waste sites. Routine clinical autoimmunity measures could be used as early effect biomarkers of environmental metal exposures.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100201"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/52/main.PMC10165442.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9446612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum autoantibodies and exploratory molecular pathways in rural miners: A pilot study","authors":"Esther Erdei ,&nbsp;Xixi Zhou ,&nbsp;Chris Shuey ,&nbsp;Nour Ass'ad ,&nbsp;Kimberly Page ,&nbsp;Bobbi Gore ,&nbsp;Chengsong Zhu ,&nbsp;Deborah Kanda ,&nbsp;Li Luo ,&nbsp;Akshay Sood ,&nbsp;Katherine E. Zychowski","doi":"10.1016/j.jtauto.2023.100197","DOIUrl":"10.1016/j.jtauto.2023.100197","url":null,"abstract":"<div><h3>Introduction</h3><p>The Southwestern United States (SWUS) has an extensive history of coal and metal mining, including uranium (U) mining. Lung diseases, including but not limited to, lung cancer and pulmonary fibrosis, have been studied extensively in miners due to occupational, dust-related exposures. However, high-throughput autoimmune biomarkers are largely understudied in miners, despite the fact that ore miners, such as U-miners, are at an increased risk for the development of autoimmune diseases such as systemic sclerosis and systemic lupus erythematosus (SLE). Additionally, there are current gaps in knowledge regarding which signaling pathways may play a role in occupational exposure-associated autoimmunity.</p></div><div><h3>Methods</h3><p>Most current and former miners in the SWUS live close to their previous workplaces, in remote areas, with limited access to healthcare. In this pilot study, by leveraging a mobile clinical platform for patient care and clinical outreach, we recruited 44 miners who self-identified as either U (n = 10) or non-U miners (n = 34) and received health screenings. Serum IgG and IgM autoantibodies against 128 antigens were assessed using a high-throughput molecular technique, as a preliminary health screening opportunity.</p></div><div><h3>Results</h3><p>Even when adjusting for age as a covariate, there was a significant (p &lt; 0.05) association between self-reported U-mining exposure and biomarkers including IgM alpha-actinin, histones H2B, and H4, myeloperoxidase (MPO) and myelin basic protein. However, adjusting for age did not result in significant associations for IgG autoantibody production in U-miners. Bioinformatic pathway analysis revealed several altered signaling pathways between IgM and IgG autoantibodies among both U and non-U miners.</p></div><div><h3>Conclusions</h3><p>Further research is warranted regarding the mechanistic connection between U-exposure and autoantibody development, especially regarding histone-related alterations and IgM autoantibody production.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100197"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/57/f8/main.PMC10023988.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9259337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies to dsDNA in the diagnosis, classification and follow-up of patients with systemic lupus erythematosus","authors":"Jan Damoiseaux,&nbsp;Joyce van Beers","doi":"10.1016/j.jtauto.2023.100191","DOIUrl":"10.1016/j.jtauto.2023.100191","url":null,"abstract":"<div><p>Autoantibodies, in particular anti-dsDNA antibodies, are increasingly used for diagnosis, classification and follow-up of patients with SLE. Since standardization of autoantibody assays is a major challenge, more attention should be paid to harmonization initiatives and better definition of required test characteristics in classification criteria. For diagnosis and follow-up separate multi-center studies are required to establish test characteristics of distinct immuno-assays for both purposes. Finally, such studies should consider not to evaluate SLE as a single disease, but as a disease with distinct subtypes.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100191"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10593352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventive plasmapheresis for rituximab related flare in cryoglobulinemic vasculitis","authors":"Léa Fornero ,&nbsp;Tarik Kanouni ,&nbsp;Jean-Jacques Tudesq ,&nbsp;Camille Pochard ,&nbsp;Pauline Verot ,&nbsp;Wendy Renier ,&nbsp;Ludovic Gabellier ,&nbsp;Guillaume Cartron ,&nbsp;Philippe Guilpain ,&nbsp;Charles Herbaux","doi":"10.1016/j.jtauto.2023.100194","DOIUrl":"10.1016/j.jtauto.2023.100194","url":null,"abstract":"<div><h3>Introduction</h3><p>Rituximab monotherapy represents the main therapeutic option for cryoglobulinemic vasculitis (CV) with severe organ involvement. However, initial worsening of the CV, known as rituximab-associated CV flare (=CV flare), has been described and are associated with high mortality rates. The aim of the present study is to evaluate the outcomes of plasmapheresis initiated before or during rituximab treatment, as prevention of CV flare.</p></div><div><h3>Methods</h3><p>We conducted a retrospecttive study in our tertiary referral center from 2001 to 2020. We have included all patients with CV receiving rituximab and divided them in two groups whether they had flare prevention by plasmapheresis or not. We evaluated rituximab-related CV flare incidence in both groups. CV flare was defined as the onset of a new organ involvement or worsening of the initial manifestations within 4 weeks following rituximab.</p></div><div><h3>Results</h3><p>Among the 71 patients included, 44 received rituximab without plasmapheresis (control = CT cohort) and 27 received plasmapheresis before or during rituximab treatment (preventive plasmapheresis = PP cohort). PP was given to patients thought to have a high risk of CV flare, with significantly more severe diseases than patients in the CT cohort. Despite this, no CV flare was observed in the PP group. In the other hand, 5 flares occurred in the CT cohort.</p></div><div><h3>Conclusion</h3><p>Our results show that plasmapheresis is efficient and well tolerated to prevent rituximab-associated CV flare. We believe that our data support the use of plasmapheresis in this indication, especially in patients with high risk of CV flare.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100194"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9975310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10845050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis – a case series","authors":"Mirjam Kolev ,&nbsp;Adela-Cristina Sarbu ,&nbsp;Burkhard Möller ,&nbsp;Britta Maurer ,&nbsp;Florian Kollert ,&nbsp;Nasser Semmo","doi":"10.1016/j.jtauto.2023.100189","DOIUrl":"10.1016/j.jtauto.2023.100189","url":null,"abstract":"<div><h3>Background</h3><p>The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.</p><p>In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the <em>anti</em>-B cell activating factor, belimumab. The first three patients had concomitant Sjögren's disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren's disease.</p></div><div><h3>Aims and methods</h3><p>To retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren's disease treated with the <em>anti</em>-BAFF therapy belimumab at the University Hospital in Bern, Switzerland.</p></div><div><h3>Results</h3><p>In all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren's disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time.</p></div><div><h3>Conclusions</h3><p>Belimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100189"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/8d/main.PMC9883290.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10590392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors of cardiovascular involvement in patients with Behcet's disease","authors":"Yuqian Wang,&nbsp;Sheng Li,&nbsp;Shunli Tang,&nbsp;Xiaoxuan Cai,&nbsp;Juan Bai,&nbsp;Qingmiao Sun,&nbsp;Jianjun Qiao,&nbsp;Hong Fang","doi":"10.1016/j.jtauto.2023.100195","DOIUrl":"10.1016/j.jtauto.2023.100195","url":null,"abstract":"<div><h3>Objectives</h3><p>Behcet's disease (BD) is a multi-systemic inflammatory vasculitis which may be life-threatening if combined with cardiovascular problems. The aim of the study was to identify potential risk factors associated with cardiovascular involvement in BD.</p></div><div><h3>Methods</h3><p>We reviewed the medical databases of a single center. All BD patients identified as fulfilling the 1990 International Study Group criteria or the International Criteria for Behcet's Disease criteria. Cardiovascular involvement, clinical manifestations, laboratory features, and treatments were recorded. The relationship between parameters and cardiovascular involvement was analyzed.</p></div><div><h3>Results</h3><p>111 BD patients were included: 21 (18.9%) had documented cardiovascular involvement (CV BD group) and 99 (81.1%) had no cardiovascular involvement (non-CV BD group). Compared with non-CV BD, the proportion of males and smokers were significantly increased in CV BD (p = 0.024 and p &lt; 0.001, respectively). Levels of activated partial thromboplastin time (APTT), cardiac troponin I and C-reactive protein were significantly higher (p = 0.001, p = 0.031, and p = 0.034, respectively) in the CV BD group. Cardiovascular involvement was associated with smoking state, the presence of papulopustular lesions, and higher APTT in multivariate analyzed (p = 0.029, p = 0.021, and p = 0.006, respectively). The ROC curve showed that APTT predicts the risk of cardiovascular involvement (p &lt; 0.01) at a cut-off value of 33.15 s with a sensitivity of 57.1% and specificity of 82.2%.</p></div><div><h3>Conclusion</h3><p>Cardiovascular involvement in BD patients was associated with gender, smoking state, the presence of papulopustular lesions, and higher APTT. All patients newly diagnosed with BD should be systematically screened for cardiovascular involvement.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100195"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/8b/main.PMC9982677.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10845049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adding low dose cyclophosphamide to rituximab for remission-induction may prolong relapse-free survival in patients with ANCA vasculitis: A retrospective study","authors":"Renée Ysermans ,&nbsp;Matthias H. Busch ,&nbsp;Joop P. Aendekerk ,&nbsp;Jan G.M.C. Damoiseaux ,&nbsp;Pieter van Paassen","doi":"10.1016/j.jtauto.2022.100178","DOIUrl":"10.1016/j.jtauto.2022.100178","url":null,"abstract":"<div><h3>Objective</h3><p>Rituximab (RTX) and cyclophosphamide (CYC) are effective remission-induction therapies in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, combining these therapies may favor prognosis in patients with a major disease presentation. We conducted a retrospective study to compare patients treated with a combination of RTX and low dose CYC (RTX-CYC) or with RTX only, both followed by tailored maintenance with RTX, with regard to long-term outcomes.</p></div><div><h3>Methods</h3><p>Patients treated in the Maastricht University Medical Center between March 2007 and January 2019, were screened for eligibility. The primary outcome variable was major relapse rate after two and five years. Secondary outcome variables were clinical data and laboratory parameters.</p></div><div><h3>Results</h3><p>Of the 246 screened patients, 34 received RTX-CYC and 28 RTX only for remission-induction. All patients were followed for at least two years, with a median follow-up of 48 months (IQR 24–60). At baseline, renal involvement was more prevalent in the RTX-CYC patients (85% vs. 61%, <em>P</em> = 0.028). Major relapse rates within two years, but not after five years, were significantly lower in the RTX-CYC group (3% vs. 24%, <em>P</em> = 0.032). The rate of infections, hypogammaglobulinemia, end-stage renal disease, malignancies, and mortality did not differ after two and five years.</p></div><div><h3>Conclusion</h3><p>Adding low dose CYC to RTX is safe and may prevent major relapses in patients with severe AAV in the first two years after remission-induction. Randomized controlled trials that compare the efficacy and safety between RTX and a combination of RTX with CYC are needed.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100178"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10471603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}