Pub Date : 2022-01-01DOI: 10.1016/b978-0-12-822564-6.00019-7
M. Cook
{"title":"Regulation of immunological tolerance and human autoimmunity by NF-κB","authors":"M. Cook","doi":"10.1016/b978-0-12-822564-6.00019-7","DOIUrl":"https://doi.org/10.1016/b978-0-12-822564-6.00019-7","url":null,"abstract":"","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"3 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85375204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1016/j.jtauto.2021.100138
Sharon Veenbergen , Ana Kozmar , Paul L.A. van Daele , Marco W.J. Schreurs
Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by immune-mediated injury of exocrine glands. Extensive lymphocytic infiltrates may contribute to the destruction and loss of secretory function of glands. B-cell hyperactivity is a key feature of the disease resulting in the production of a diverse array of autoantibodies in these patients. Although not specific for SS, anti-Ro/SSA and anti-La/SSB antibodies have been useful biomarkers for disease classification and diagnosis. During recent years, novel autoantibodies have been discovered in SS. In this review, we summarize the historical role and clinical relevance that autoantibodies have played in the classification criteria of Sjögren's syndrome, discuss laboratory aspects in antibody detection and review the role of novel autoantibodies in predicting particular stages of the disease, clinical phenotypes and long-term complications.
{"title":"Autoantibodies in Sjögren's syndrome and its classification criteria","authors":"Sharon Veenbergen , Ana Kozmar , Paul L.A. van Daele , Marco W.J. Schreurs","doi":"10.1016/j.jtauto.2021.100138","DOIUrl":"10.1016/j.jtauto.2021.100138","url":null,"abstract":"<div><p>Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by immune-mediated injury of exocrine glands. Extensive lymphocytic infiltrates may contribute to the destruction and loss of secretory function of glands. B-cell hyperactivity is a key feature of the disease resulting in the production of a diverse array of autoantibodies in these patients. Although not specific for SS, anti-Ro/SSA and anti-La/SSB antibodies have been useful biomarkers for disease classification and diagnosis. During recent years, novel autoantibodies have been discovered in SS. In this review, we summarize the historical role and clinical relevance that autoantibodies have played in the classification criteria of Sjögren's syndrome, discuss laboratory aspects in antibody detection and review the role of novel autoantibodies in predicting particular stages of the disease, clinical phenotypes and long-term complications.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"5 ","pages":"Article 100138"},"PeriodicalIF":3.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5b/d8/main.PMC8728464.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816830","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}
Pub Date : 2022-01-01DOI: 10.1016/j.jtauto.2022.100142
Lieve Van Hoovels , Paul Studenic , Daniela Sieghart , Günter Steiner , Xavier Bossuyt , Johan Rönnelid
Rheumatoid arthritis (RA) is the most common systemic autoimmune disease and also the most severe arthritic disorder. The measurement of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) in serum supports the diagnosis of RA, which gained increasing significance over the last 65 years. However, a high variability between RF and ACPA methods has been described, impacting the diagnostic performance of the current ACR/EULAR RA classification criteria.
The great number of commercially available assays, often lacking traceability to an international standard, is a major factor attributing to this in-between assay variability. The adoption of an international standard for ACPA, as is since long available for rheumatoid factor, is therefore highly desirable.
Further harmonization in clinical interpretation of RF/ACPA assays could be obtained by harmonization of the cut-offs, for both the low and high antibody levels, based on predefined specificity in disease controls. Reporting test result specific likelihood ratios (LR) adds value in the interpretation of autoantibody tests. However, a good understanding of the control population used to define antibody test result interval-associated LRs is crucial in defining the diagnostic performance characteristics of antibody serology.
Finally, specificity in RA classification can be improved by refining serological weight scoring taking into account the nature of the antibody, the antibody level and double RF + ACPA positivity.
{"title":"Impact of autoimmune serology test results on RA classification and diagnosis","authors":"Lieve Van Hoovels , Paul Studenic , Daniela Sieghart , Günter Steiner , Xavier Bossuyt , Johan Rönnelid","doi":"10.1016/j.jtauto.2022.100142","DOIUrl":"10.1016/j.jtauto.2022.100142","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) is the most common systemic autoimmune disease and also the most severe arthritic disorder. The measurement of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) in serum supports the diagnosis of RA, which gained increasing significance over the last 65 years. However, a high variability between RF and ACPA methods has been described, impacting the diagnostic performance of the current ACR/EULAR RA classification criteria.</p><p>The great number of commercially available assays, often lacking traceability to an international standard, is a major factor attributing to this in-between assay variability. The adoption of an international standard for ACPA, as is since long available for rheumatoid factor, is therefore highly desirable.</p><p>Further harmonization in clinical interpretation of RF/ACPA assays could be obtained by harmonization of the cut-offs, for both the low and high antibody levels, based on predefined specificity in disease controls. Reporting test result specific likelihood ratios (LR) adds value in the interpretation of autoantibody tests. However, a good understanding of the control population used to define antibody test result interval-associated LRs is crucial in defining the diagnostic performance characteristics of antibody serology.</p><p>Finally, specificity in RA classification can be improved by refining serological weight scoring taking into account the nature of the antibody, the antibody level and double RF + ACPA positivity.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"5 ","pages":"Article 100142"},"PeriodicalIF":3.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/4f/main.PMC8749172.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39827864","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}
Pub Date : 2022-01-01DOI: 10.1016/j.jtauto.2022.100151
Mirjam Kolev , Michael P. Horn , Nasser Semmo , Michael Nagler
Clear guidance is needed in the development and implementation of laboratory biomarkers in medicine. So far, no standardized phased approach is established that would pilot researchers and clinicians in this process. This leads to often incompletely validated biomarkers, which can bear the consequence of wrong applications, misinterpretation and inadequate management in the clinical context.
In this conceptual article, we describe a stepwise approach to develop and comprehensively validate laboratory biomarkers. We will delineate basic steps including technical performance, pre-analytical issues, and biological variation, as well as advanced aspects of biomarker utility comprising interpretability, diagnostic and prognostic accuracy, and health-care outcomes. These aspects will be illustrated by using well-known examples from the field of immunology.
The application of this conceptual framework will guide researchers in conducting meaningful projects to develop and evaluate biomarkers for the use in clinical practice. Furthermore, clinicians will be able to adequately interpret pre-clinical and clinical diagnostic literature and rationally apply biomarkers in clinical practice. Improvement in the implementation and application of biomarkers might relevantly change the management and outcomes of our patients for the better.
{"title":"Rational development and application of biomarkers in the field of autoimmunity: A conceptual framework guiding clinicians and researchers","authors":"Mirjam Kolev , Michael P. Horn , Nasser Semmo , Michael Nagler","doi":"10.1016/j.jtauto.2022.100151","DOIUrl":"10.1016/j.jtauto.2022.100151","url":null,"abstract":"<div><p>Clear guidance is needed in the development and implementation of laboratory biomarkers in medicine. So far, no standardized phased approach is established that would pilot researchers and clinicians in this process. This leads to often incompletely validated biomarkers, which can bear the consequence of wrong applications, misinterpretation and inadequate management in the clinical context.</p><p>In this conceptual article, we describe a stepwise approach to develop and comprehensively validate laboratory biomarkers. We will delineate basic steps including technical performance, pre-analytical issues, and biological variation, as well as advanced aspects of biomarker utility comprising interpretability, diagnostic and prognostic accuracy, and health-care outcomes. These aspects will be illustrated by using well-known examples from the field of immunology.</p><p>The application of this conceptual framework will guide researchers in conducting meaningful projects to develop and evaluate biomarkers for the use in clinical practice. Furthermore, clinicians will be able to adequately interpret pre-clinical and clinical diagnostic literature and rationally apply biomarkers in clinical practice. Improvement in the implementation and application of biomarkers might relevantly change the management and outcomes of our patients for the better.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"5 ","pages":"Article 100151"},"PeriodicalIF":3.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40309435","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}
Pub Date : 2022-01-01DOI: 10.1016/j.jtauto.2022.100172
Mirjam Kolev , Stefan Diem , Lara Diem , Susana G. Rodrigues , Annalisa Berzigotti , Guido Stirnimann , Nasser Semmo
Background
Most patients with autoimmune hepatitis respond to standard treatment with steroids and azathioprine. While the disease is usually fatal if untreated, patients who respond well to therapy have an excellent prognosis. Nevertheless, second-line treatment is necessary in approximately 20% of patients, due to either intolerance or insufficient response to first line treatment.
While data for mycophenolate mofetil (MMF) in patients intolerant to azathioprine is encouraging, MMF seems of less benefit in patients with insufficient response to first line treatment, but analyzed data on this issue is limited.
Aim
To evaluate the efficacy and safety of MMF as a second-line therapy in patients with AIH.
Methods
Retrospective analysis of a monocentric database of AIH patients who received medical care from 2000 to 2022. Clinical, immunological and biochemical parameters were assessed at different time points including last follow-up.
Results
Overall, 144 patients with AIH were identified. Fifty out of 144 (35%) AIH patients received MMF. Forty (80%) received MMF due to first line treatment intolerance, while ten (20%) due to insufficient response to first line treatment.
Remission with MMF monotherapy was 81.5% in the intolerance group versus 30% in the insufficient response group. Patients switched to MMF because of an insufficient response, more often needed additional prednisolone doses higher than 5 mg/day, a switch to third-line treatment or combination regiments, to achieve disease control.
Conclusions
Patients treated with MMF because of intolerance to first line treatment show a good disease control under MMF in the majority of cases. Efficacy is considerably lower in the patients switched to MMF because of an insufficient response to first line treatment.
{"title":"Mycophenolate mofetil as second line treatment in autoimmune hepatitis – A retrospective single center analysis","authors":"Mirjam Kolev , Stefan Diem , Lara Diem , Susana G. Rodrigues , Annalisa Berzigotti , Guido Stirnimann , Nasser Semmo","doi":"10.1016/j.jtauto.2022.100172","DOIUrl":"10.1016/j.jtauto.2022.100172","url":null,"abstract":"<div><h3>Background</h3><p>Most patients with autoimmune hepatitis respond to standard treatment with steroids and azathioprine. While the disease is usually fatal if untreated, patients who respond well to therapy have an excellent prognosis. Nevertheless, second-line treatment is necessary in approximately 20% of patients, due to either intolerance or insufficient response to first line treatment.</p><p>While data for mycophenolate mofetil (MMF) in patients intolerant to azathioprine is encouraging, MMF seems of less benefit in patients with insufficient response to first line treatment, but analyzed data on this issue is limited.</p></div><div><h3>Aim</h3><p>To evaluate the efficacy and safety of MMF as a second-line therapy in patients with AIH.</p></div><div><h3>Methods</h3><p>Retrospective analysis of a monocentric database of AIH patients who received medical care from 2000 to 2022. Clinical, immunological and biochemical parameters were assessed at different time points including last follow-up.</p></div><div><h3>Results</h3><p>Overall, 144 patients with AIH were identified. Fifty out of 144 (35%) AIH patients received MMF. Forty (80%) received MMF due to first line treatment intolerance, while ten (20%) due to insufficient response to first line treatment.</p><p>Remission with MMF monotherapy was 81.5% in the intolerance group versus 30% in the insufficient response group. Patients switched to MMF because of an insufficient response, more often needed additional prednisolone doses higher than 5 mg/day, a switch to third-line treatment or combination regiments, to achieve disease control.</p></div><div><h3>Conclusions</h3><p>Patients treated with MMF because of intolerance to first line treatment show a good disease control under MMF in the majority of cases. Efficacy is considerably lower in the patients switched to MMF because of an insufficient response to first line treatment.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"5 ","pages":"Article 100172"},"PeriodicalIF":3.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9702977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40490680","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}
Pub Date : 2022-01-01DOI: 10.1016/j.jtauto.2022.100153
Harini Bagavant , Katarzyna Cizio , Antonina M. Araszkiewicz , Joanna A. Papinska , Lori Garman , Chuang Li , Nathan Pezant , Wonder P. Drake , Courtney G. Montgomery , Umesh S. Deshmukh
A characteristic feature of sarcoidosis is a dysregulated immune response to persistent stimuli, often leading to the formation of non-necrotizing granulomas in various organs. Although genetic susceptibility is an essential factor in disease development, the etiology of sarcoidosis is not fully understood. Specifically, whether autoimmunity contributes to the initiation or progression of the disease is uncertain. In this study, we investigated systemic autoimmunity to vimentin in sarcoidosis. IgG antibodies to human vimentin were measured in sera from sarcoidosis patients and healthy controls. Mice immunized with recombinant murine vimentin were challenged intravenously with vimentin-coated beads to mimic pulmonary sarcoidosis. Lungs from treated mice were studied for cellular infiltration, granuloma formation, and gene expression. Immune cells in the bronchoalveolar lavage fluid were evaluated by flow cytometry. Compared to healthy controls, sarcoidosis patients had a higher frequency and levels of circulating anti-vimentin IgG. Vimentin-immunized mice developed lung granulomas following intravenous challenge with vimentin-coated beads. These sarcoidosis-like granulomas showed the presence of Langhans and foreign body multinucleated giant cells, CD4 T cells, and a heterogeneous collection of MHC II positive and arginase 1-expressing macrophages. The lungs showed upregulated pro-inflammatory gene expression, including Ifng, Il17, and Tnfa, reflecting TH1/TH17 responses typical of sarcoidosis. In addition, genes in the TH2 canonical pathway were also upregulated, congruent with increased numbers of ILC2 in the bronchoalveolar lavage. Overall, these results further validate vimentin as an autoantigen in sarcoidosis and provide evidence for an anti-vimentin immune response in disease pathogenesis. Our study also highlights the possible role of ILC2-driven TH2-like responses in the formation of lung granulomas in sarcoidosis.
{"title":"Systemic immune response to vimentin and granuloma formation in a model of pulmonary sarcoidosis","authors":"Harini Bagavant , Katarzyna Cizio , Antonina M. Araszkiewicz , Joanna A. Papinska , Lori Garman , Chuang Li , Nathan Pezant , Wonder P. Drake , Courtney G. Montgomery , Umesh S. Deshmukh","doi":"10.1016/j.jtauto.2022.100153","DOIUrl":"10.1016/j.jtauto.2022.100153","url":null,"abstract":"<div><p>A characteristic feature of sarcoidosis is a dysregulated immune response to persistent stimuli, often leading to the formation of non-necrotizing granulomas in various organs. Although genetic susceptibility is an essential factor in disease development, the etiology of sarcoidosis is not fully understood. Specifically, whether autoimmunity contributes to the initiation or progression of the disease is uncertain. In this study, we investigated systemic autoimmunity to vimentin in sarcoidosis. IgG antibodies to human vimentin were measured in sera from sarcoidosis patients and healthy controls. Mice immunized with recombinant murine vimentin were challenged intravenously with vimentin-coated beads to mimic pulmonary sarcoidosis. Lungs from treated mice were studied for cellular infiltration, granuloma formation, and gene expression. Immune cells in the bronchoalveolar lavage fluid were evaluated by flow cytometry. Compared to healthy controls, sarcoidosis patients had a higher frequency and levels of circulating anti-vimentin IgG. Vimentin-immunized mice developed lung granulomas following intravenous challenge with vimentin-coated beads. These sarcoidosis-like granulomas showed the presence of Langhans and foreign body multinucleated giant cells, CD4 T cells, and a heterogeneous collection of MHC II positive and arginase 1-expressing macrophages. The lungs showed upregulated pro-inflammatory gene expression, including <em>Ifng</em>, <em>Il17,</em> and <em>Tnfa,</em> reflecting TH1/TH17 responses typical of sarcoidosis. In addition, genes in the TH2 canonical pathway were also upregulated, congruent with increased numbers of ILC2 in the bronchoalveolar lavage. Overall, these results further validate vimentin as an autoantigen in sarcoidosis and provide evidence for an anti-vimentin immune response in disease pathogenesis. Our study also highlights the possible role of ILC2-driven TH2-like responses in the formation of lung granulomas in sarcoidosis.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"5 ","pages":"Article 100153"},"PeriodicalIF":3.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909022000144/pdfft?md5=3e24074abe356b20c4ab9548e02bf283&pid=1-s2.0-S2589909022000144-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47510273","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}
Pub Date : 2022-01-01DOI: 10.1016/b978-0-12-824390-9.00018-9
N. Sturm, B. Huard
{"title":"Plasmocyte depletion in autoimmune diseases","authors":"N. Sturm, B. Huard","doi":"10.1016/b978-0-12-824390-9.00018-9","DOIUrl":"https://doi.org/10.1016/b978-0-12-824390-9.00018-9","url":null,"abstract":"","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"130 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79595266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}