Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura
Immune thrombotic thrombocytopenic purpura (iTTP) is an autoimmune disorder of which the etiology is not fully understood. Autoantibodies targeting ADAMTS13 in iTTP patients have extensively been studied, the immunological mechanisms leading to the breach of tolerance remain to be uncovered. This re...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.757192/full |
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| author | Aicha Laghmouchi Nuno A. G. Graça Jan Voorberg |
| author_facet | Aicha Laghmouchi Nuno A. G. Graça Jan Voorberg |
| author_sort | Aicha Laghmouchi |
| collection | DOAJ |
| description | Immune thrombotic thrombocytopenic purpura (iTTP) is an autoimmune disorder of which the etiology is not fully understood. Autoantibodies targeting ADAMTS13 in iTTP patients have extensively been studied, the immunological mechanisms leading to the breach of tolerance remain to be uncovered. This review addresses the current knowledge on genetic factors associated with the development of iTTP and the interplay between the patient’s immune system and environmental factors in the induction of autoimmunity against ADAMTS13. HLA-DRB1*11 has been identified as a risk factor for iTTP in the Caucasian population. Interestingly, HLA-DRB1*08:03 was recently identified as a risk factor in the Japanese population. Combined in vitro and in silico MHC class II peptide presentation approaches suggest that an ADAMTS13-derived peptide may bind to both HLA-DRB1*11 and HLA-DRB1*08:03 through different anchor-residues. It is apparent that iTTP is associated with the presence of infectious microorganisms, viruses being the most widely associated with development of iTTP. Infections may potentially lead to loss of tolerance resulting in the shift from immune homeostasis to autoimmunity. In the model we propose in this review, infections disrupt the epithelial barriers in the gut or lung, promoting exposure of antigen presenting cells in the mucosa-associated lymphoid tissue to the microorganisms. This may result in breach of tolerance through the presentation of microorganism-derived peptides that are homologous to ADAMTS13 on risk alleles for iTTP. |
| first_indexed | 2024-12-20T23:19:54Z |
| format | Article |
| id | doaj.art-60f39ee536b34888bd6fb970198502b0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T23:19:54Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-60f39ee536b34888bd6fb970198502b02022-12-21T19:23:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.757192757192Emerging Concepts in Immune Thrombotic Thrombocytopenic PurpuraAicha LaghmouchiNuno A. G. GraçaJan VoorbergImmune thrombotic thrombocytopenic purpura (iTTP) is an autoimmune disorder of which the etiology is not fully understood. Autoantibodies targeting ADAMTS13 in iTTP patients have extensively been studied, the immunological mechanisms leading to the breach of tolerance remain to be uncovered. This review addresses the current knowledge on genetic factors associated with the development of iTTP and the interplay between the patient’s immune system and environmental factors in the induction of autoimmunity against ADAMTS13. HLA-DRB1*11 has been identified as a risk factor for iTTP in the Caucasian population. Interestingly, HLA-DRB1*08:03 was recently identified as a risk factor in the Japanese population. Combined in vitro and in silico MHC class II peptide presentation approaches suggest that an ADAMTS13-derived peptide may bind to both HLA-DRB1*11 and HLA-DRB1*08:03 through different anchor-residues. It is apparent that iTTP is associated with the presence of infectious microorganisms, viruses being the most widely associated with development of iTTP. Infections may potentially lead to loss of tolerance resulting in the shift from immune homeostasis to autoimmunity. In the model we propose in this review, infections disrupt the epithelial barriers in the gut or lung, promoting exposure of antigen presenting cells in the mucosa-associated lymphoid tissue to the microorganisms. This may result in breach of tolerance through the presentation of microorganism-derived peptides that are homologous to ADAMTS13 on risk alleles for iTTP.https://www.frontiersin.org/articles/10.3389/fimmu.2021.757192/fullTTP (thrombotic thrombocytopenic purpura)DRB1*11DRB1*08infection-immunologymicrobiotatolerance |
| spellingShingle | Aicha Laghmouchi Nuno A. G. Graça Jan Voorberg Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura Frontiers in Immunology TTP (thrombotic thrombocytopenic purpura) DRB1*11 DRB1*08 infection-immunology microbiota tolerance |
| title | Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura |
| title_full | Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura |
| title_fullStr | Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura |
| title_full_unstemmed | Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura |
| title_short | Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura |
| title_sort | emerging concepts in immune thrombotic thrombocytopenic purpura |
| topic | TTP (thrombotic thrombocytopenic purpura) DRB1*11 DRB1*08 infection-immunology microbiota tolerance |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.757192/full |
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