Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura
Autoantibodies to ADAMTS13 are at the center of pathology of the immune-mediated thrombotic thrombocytopenic purpura. These autoantibodies can be either inhibitory (enzymatic function) or non-inhibitory, resulting in protein depletion. Under normal physiologic conditions, antibodies are generated in...
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MDPI AG
2025-03-01
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| author | Michael R. Snyder Robert W. Maitta |
| author_facet | Michael R. Snyder Robert W. Maitta |
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| description | Autoantibodies to ADAMTS13 are at the center of pathology of the immune-mediated thrombotic thrombocytopenic purpura. These autoantibodies can be either inhibitory (enzymatic function) or non-inhibitory, resulting in protein depletion. Under normal physiologic conditions, antibodies are generated in response to foreign antigens, which can include infectious agents; however, these antibodies may at times cross-react with self-epitopes. This is one of the possible mechanisms mediating formation of anti-ADAMTS13 autoantibodies. The process known as “antigenic mimicry” may be responsible for the development of these autoantibodies that recognize and bind cryptic epitopes in ADAMTS13, disrupting its enzymatic function over ultra large von Willebrand factor multimers, forming the seeds for platelet activation and microthrombi formation. In particular, specific amino acid sequences in ADAMTS13 may lead to conformational structures recognized by autoantibodies. Generation of these antibodies may occur more frequently among patients with a genetic predisposition. Conformational changes in ADAMTS13 between open and closed states can also constitute the critical change driving either interactions with autoantibodies or their generation. Nowadays, there is a growing understanding of the role that autoantibodies play in ADAMTS13 pathology. This knowledge, especially of functional qualitative differences among antibodies and the ADAMTS13 sequence specificity of such antibodies, may make possible the development of targeted therapeutic agents to treat the disease. This review aims to present what is known of autoantibodies against ADAMTS13 and how their structure and function result in disease. |
| format | Article |
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| institution | OA Journals |
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| language | English |
| publishDate | 2025-03-01 |
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| series | Antibodies |
| spelling | doaj-art-de62a4ba44b3446280bcb19bec44be112025-08-20T02:11:17ZengMDPI AGAntibodies2073-44682025-03-011412410.3390/antib14010024Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic PurpuraMichael R. Snyder0Robert W. Maitta1Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USADepartment of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USAAutoantibodies to ADAMTS13 are at the center of pathology of the immune-mediated thrombotic thrombocytopenic purpura. These autoantibodies can be either inhibitory (enzymatic function) or non-inhibitory, resulting in protein depletion. Under normal physiologic conditions, antibodies are generated in response to foreign antigens, which can include infectious agents; however, these antibodies may at times cross-react with self-epitopes. This is one of the possible mechanisms mediating formation of anti-ADAMTS13 autoantibodies. The process known as “antigenic mimicry” may be responsible for the development of these autoantibodies that recognize and bind cryptic epitopes in ADAMTS13, disrupting its enzymatic function over ultra large von Willebrand factor multimers, forming the seeds for platelet activation and microthrombi formation. In particular, specific amino acid sequences in ADAMTS13 may lead to conformational structures recognized by autoantibodies. Generation of these antibodies may occur more frequently among patients with a genetic predisposition. Conformational changes in ADAMTS13 between open and closed states can also constitute the critical change driving either interactions with autoantibodies or their generation. Nowadays, there is a growing understanding of the role that autoantibodies play in ADAMTS13 pathology. This knowledge, especially of functional qualitative differences among antibodies and the ADAMTS13 sequence specificity of such antibodies, may make possible the development of targeted therapeutic agents to treat the disease. This review aims to present what is known of autoantibodies against ADAMTS13 and how their structure and function result in disease.https://www.mdpi.com/2073-4468/14/1/24ADAMTS13autoantibodyvon Willebrand factorthrombotic thrombocytopenic purpuraiTTPstructure |
| spellingShingle | Michael R. Snyder Robert W. Maitta Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura Antibodies ADAMTS13 autoantibody von Willebrand factor thrombotic thrombocytopenic purpura iTTP structure |
| title | Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura |
| title_full | Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura |
| title_fullStr | Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura |
| title_full_unstemmed | Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura |
| title_short | Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura |
| title_sort | anti adamts13 autoantibodies in immune mediated thrombotic thrombocytopenic purpura |
| topic | ADAMTS13 autoantibody von Willebrand factor thrombotic thrombocytopenic purpura iTTP structure |
| url | https://www.mdpi.com/2073-4468/14/1/24 |
| work_keys_str_mv | AT michaelrsnyder antiadamts13autoantibodiesinimmunemediatedthromboticthrombocytopenicpurpura AT robertwmaitta antiadamts13autoantibodiesinimmunemediatedthromboticthrombocytopenicpurpura |