{"title":"Lyn/CD22/SHP-1 and their importance in autoimmunity.","authors":"J. Blasioli, C. Goodnow","doi":"10.1159/000060551","DOIUrl":"https://doi.org/10.1159/000060551","url":null,"abstract":"","PeriodicalId":81058,"journal":{"name":"Current directions in autoimmunity","volume":"5 1","pages":"151-60"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000060551","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65043899","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}
Recent studies on the nature and mode of action of inhibitory receptors and their intracellular phosphatase effector enzymes have identified a new area of research in the etiology of autoimmune diseases. Myeloid cells play a critical role in autoimmunity through their IgG receptors. A number of recent findings reveal that such cells express inhibitory receptors, including the elusive CD32/Fc gamma RIIB isoform, and express inhibitory phosphatases like SHP-1 and SHIP. Animals lacking the effector phosphatases exhibit a pronounced autoimmune and/or pro-inflammatory phenotype. Animals deficient in the expression of the inhibitory receptors often display a much less severe phenotype, likely due to the fact that hematopoietic cells have numerous and probably redundant inhibitory receptors. Genetic deficiencies in the limited number of effector molecules (SHP-1 and SHIP) lead to more dramatic effects on hematopoietic cells and level of inflammation in such animals. These recent findings in animal models open the intriguing possibility that the human homologues of genes encoding the inhibitory receptors like Fc gamma RIIB or effector phosphatases like SHIP might contribute to autoimmune diseases. However, while identification of genes involved in autoimmunity will greatly aid in diagnosis of human autoimmune disease, it is necessary to understand the biochemical mechanisms of action of the numerous inhibitory receptors and phosphatases in the hematopoietic system. Such information will permit the rational design of more efficient and effective treatments for patients. Additional experiments directed at the role and mechanism(s) of action of the inhibitory phosphatases SHP-1 and SHIP will uncover new candidates for diagnosis and treatment of autoimmune diseases.
{"title":"Regulation of signal transduction by the Fc gamma receptor family members and their involvement in autoimmunity.","authors":"K. Coggeshall","doi":"10.1159/000060554","DOIUrl":"https://doi.org/10.1159/000060554","url":null,"abstract":"Recent studies on the nature and mode of action of inhibitory receptors and their intracellular phosphatase effector enzymes have identified a new area of research in the etiology of autoimmune diseases. Myeloid cells play a critical role in autoimmunity through their IgG receptors. A number of recent findings reveal that such cells express inhibitory receptors, including the elusive CD32/Fc gamma RIIB isoform, and express inhibitory phosphatases like SHP-1 and SHIP. Animals lacking the effector phosphatases exhibit a pronounced autoimmune and/or pro-inflammatory phenotype. Animals deficient in the expression of the inhibitory receptors often display a much less severe phenotype, likely due to the fact that hematopoietic cells have numerous and probably redundant inhibitory receptors. Genetic deficiencies in the limited number of effector molecules (SHP-1 and SHIP) lead to more dramatic effects on hematopoietic cells and level of inflammation in such animals. These recent findings in animal models open the intriguing possibility that the human homologues of genes encoding the inhibitory receptors like Fc gamma RIIB or effector phosphatases like SHIP might contribute to autoimmune diseases. However, while identification of genes involved in autoimmunity will greatly aid in diagnosis of human autoimmune disease, it is necessary to understand the biochemical mechanisms of action of the numerous inhibitory receptors and phosphatases in the hematopoietic system. Such information will permit the rational design of more efficient and effective treatments for patients. Additional experiments directed at the role and mechanism(s) of action of the inhibitory phosphatases SHP-1 and SHIP will uncover new candidates for diagnosis and treatment of autoimmune diseases.","PeriodicalId":81058,"journal":{"name":"Current directions in autoimmunity","volume":"5 1","pages":"1-29"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000060554","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65043951","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}
{"title":"CD40 signaling and autoimmunity.","authors":"G. Cheng, S. Schoenberger","doi":"10.1159/000060547","DOIUrl":"https://doi.org/10.1159/000060547","url":null,"abstract":"","PeriodicalId":81058,"journal":{"name":"Current directions in autoimmunity","volume":"1 1","pages":"51-61"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000060547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65043119","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}
G. Kollias, D. Kontoyiannis, E. Douni, G. Kassiotis
{"title":"The role of TNF/TNFR in organ-specific and systemic autoimmunity: implications for the design of optimized 'anti-TNF' therapies.","authors":"G. Kollias, D. Kontoyiannis, E. Douni, G. Kassiotis","doi":"10.1159/000060546","DOIUrl":"https://doi.org/10.1159/000060546","url":null,"abstract":"","PeriodicalId":81058,"journal":{"name":"Current directions in autoimmunity","volume":"5 1","pages":"30-50"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000060546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65043299","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}
{"title":"Immunotherapy of type 1 diabetes mellitus.","authors":"L. Chatenoud","doi":"10.1159/000060543","DOIUrl":"https://doi.org/10.1159/000060543","url":null,"abstract":"","PeriodicalId":81058,"journal":{"name":"Current directions in autoimmunity","volume":"4 1","pages":"333-50"},"PeriodicalIF":0.0,"publicationDate":"2001-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000060543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65042883","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}
M. V. von Herrath, M. Oldstone, D. Homann, U. Christen
Viral infections are implicated in the pathogenesis of autoimmune disorders through several mechanisms [1–12]. Many of these rely on the fact that potentially autoreactive but resting lymphocytes, which ‘escaped’ thymic negative selection, are present in the periphery of most individuals [13–16]. There are multiple ‘built-in’ safety mechanisms to prevent the activation of these cells under normal circumstances. However, an external inflammatory insult such as a viral infection leading to immune activation could disturb the carefully established equilibrium of self-tolerance [6, 17, 18]. Various virus-induced mechanisms that break ‘tolerance’ or ‘unresponsiveness’ to self are discussed in this chapter. However, direct evidence for viral infections causing autoimmune diseases has been difficult to obtain in humans. One reason is that humans are exposed to a multitude of infections during lifetime and therefore a direct causal association between a particular virus and a disease is hard to establish. The second reason is that viruses have the ability to mutate frequently and one strain can contain multiple different sequences (‘quasi-species’) that can differ in their diabetogenicity. Last, some viral infections disrupt autoimmune processes and provide, at least in experimental models, a cure from disease. Several animal models have been generated to create conditions under which viruses induce or dampen autoimmunity and to analyze the principles by which this can occur [19, 20]. These models serve as valuable tools for understanding
{"title":"Is activation of autoreactive lymphocytes always detrimental? Viral infections and regulatory circuits in autoimmunity.","authors":"M. V. von Herrath, M. Oldstone, D. Homann, U. Christen","doi":"10.1159/000060534","DOIUrl":"https://doi.org/10.1159/000060534","url":null,"abstract":"Viral infections are implicated in the pathogenesis of autoimmune disorders through several mechanisms [1–12]. Many of these rely on the fact that potentially autoreactive but resting lymphocytes, which ‘escaped’ thymic negative selection, are present in the periphery of most individuals [13–16]. There are multiple ‘built-in’ safety mechanisms to prevent the activation of these cells under normal circumstances. However, an external inflammatory insult such as a viral infection leading to immune activation could disturb the carefully established equilibrium of self-tolerance [6, 17, 18]. Various virus-induced mechanisms that break ‘tolerance’ or ‘unresponsiveness’ to self are discussed in this chapter. However, direct evidence for viral infections causing autoimmune diseases has been difficult to obtain in humans. One reason is that humans are exposed to a multitude of infections during lifetime and therefore a direct causal association between a particular virus and a disease is hard to establish. The second reason is that viruses have the ability to mutate frequently and one strain can contain multiple different sequences (‘quasi-species’) that can differ in their diabetogenicity. Last, some viral infections disrupt autoimmune processes and provide, at least in experimental models, a cure from disease. Several animal models have been generated to create conditions under which viruses induce or dampen autoimmunity and to analyze the principles by which this can occur [19, 20]. These models serve as valuable tools for understanding","PeriodicalId":81058,"journal":{"name":"Current directions in autoimmunity","volume":"4 1","pages":"91-122"},"PeriodicalIF":0.0,"publicationDate":"2001-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000060534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65042629","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}
R. Holmdahl, R. Bockermann, J. Jirholt, Å. Johansson, P. Olofsson, S. Lu
{"title":"Elucidation of pathways leading to rheumatoid arthritis by genetic analysis of animal models.","authors":"R. Holmdahl, R. Bockermann, J. Jirholt, Å. Johansson, P. Olofsson, S. Lu","doi":"10.1159/000060519","DOIUrl":"https://doi.org/10.1159/000060519","url":null,"abstract":"","PeriodicalId":81058,"journal":{"name":"Current directions in autoimmunity","volume":"3 1","pages":"17-35"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000060519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65042070","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}
A shared attribute of many autoimmune diseases is a humoral response directed against multiple target antigens [1, 2]. The immunological diagnosis of autoimmune diseases relies mainly on the detection of autoantibodies in the serum of patients [3]. Although their pathogenic significance is still unclear, they have the great advantage of serving as constitutive markers for specific autoimmune responses. They are also important tools for the molecular cloning, identification and characterization of novel autoantigens [4, 5]. Cloned autoantigens represent an unlimited source of reagents that can be used for experimental and diagnostic purposes. In addition to studying the immunological properties of autoantigens, these molecules can readily be utilized to optimize fluid-phase radioimmunoassays [6], which in turn have future diagnostic purposes [7, 8]. For some diseases, such as autoimmune diabetes, autoimmune connective tissue diseases, systemic lupus erythematosus (SLE), autoimmune thyroid disease (AITD), rheumatoid arthritis (RA) and other chronic systemic autoimmune diseases, recombinant proteins can be utilized to devise some of the most sensitive and specific biochemical assays currently available for autoantibody detection [5, 9]. In the majority of chronic autoimmune disorders for which a diagnosis has been established, antibody laboratory testing is instrumental in decision-making for disease management based on the identification of disease activity. Autoantibodies are some of the most potent risk determinants for autoimmune diseases with relative risk exceeding 100 [10–12]. The quintessential model for the application of autoantibody markers in the prediction of a selective immune-mediated tissue damage is type 1 diabetes (T1D) and this concept
{"title":"Autoantibodies in human diabetes.","authors":"Massimo Pietropaolo, G. Eisenbarth","doi":"10.1159/000060541","DOIUrl":"https://doi.org/10.1159/000060541","url":null,"abstract":"A shared attribute of many autoimmune diseases is a humoral response directed against multiple target antigens [1, 2]. The immunological diagnosis of autoimmune diseases relies mainly on the detection of autoantibodies in the serum of patients [3]. Although their pathogenic significance is still unclear, they have the great advantage of serving as constitutive markers for specific autoimmune responses. They are also important tools for the molecular cloning, identification and characterization of novel autoantigens [4, 5]. Cloned autoantigens represent an unlimited source of reagents that can be used for experimental and diagnostic purposes. In addition to studying the immunological properties of autoantigens, these molecules can readily be utilized to optimize fluid-phase radioimmunoassays [6], which in turn have future diagnostic purposes [7, 8]. For some diseases, such as autoimmune diabetes, autoimmune connective tissue diseases, systemic lupus erythematosus (SLE), autoimmune thyroid disease (AITD), rheumatoid arthritis (RA) and other chronic systemic autoimmune diseases, recombinant proteins can be utilized to devise some of the most sensitive and specific biochemical assays currently available for autoantibody detection [5, 9]. In the majority of chronic autoimmune disorders for which a diagnosis has been established, antibody laboratory testing is instrumental in decision-making for disease management based on the identification of disease activity. Autoantibodies are some of the most potent risk determinants for autoimmune diseases with relative risk exceeding 100 [10–12]. The quintessential model for the application of autoantibody markers in the prediction of a selective immune-mediated tissue damage is type 1 diabetes (T1D) and this concept","PeriodicalId":81058,"journal":{"name":"Current directions in autoimmunity","volume":"4 1","pages":"252-82"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000060541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65043033","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}
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