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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Aicha Laghmouchi, Nuno A. G. Graça, Jan Voorberg
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	TTP (thrombotic thrombocytopenic purpura) DRB111 DRB108 infection-immunology microbiota tolerance Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/60f39ee536b34888bd6fb970198502b0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:60f39ee536b34888bd6fb970198502b0
record_format	dspace
spelling	oai:doaj.org-article:60f39ee536b34888bd6fb970198502b02021-11-11T06:26:24ZEmerging Concepts in Immune Thrombotic Thrombocytopenic Purpura1664-322410.3389/fimmu.2021.757192https://doaj.org/article/60f39ee536b34888bd6fb970198502b02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.757192/fullhttps://doaj.org/toc/1664-3224Immune 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-DRB111 has been identified as a risk factor for iTTP in the Caucasian population. Interestingly, HLA-DRB108:03 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-DRB111 and HLA-DRB108:03 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.Aicha LaghmouchiNuno A. G. GraçaJan VoorbergFrontiers Media S.A.articleTTP (thrombotic thrombocytopenic purpura)DRB111DRB108infection-immunologymicrobiotatoleranceImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TTP (thrombotic thrombocytopenic purpura) DRB111 DRB108 infection-immunology microbiota tolerance Immunologic diseases. Allergy RC581-607
spellingShingle	TTP (thrombotic thrombocytopenic purpura) DRB111 DRB108 infection-immunology microbiota tolerance Immunologic diseases. Allergy RC581-607 Aicha Laghmouchi Nuno A. G. Graça Jan Voorberg Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura
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-DRB111 has been identified as a risk factor for iTTP in the Caucasian population. Interestingly, HLA-DRB108:03 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-DRB111 and HLA-DRB108:03 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.
format	article
author	Aicha Laghmouchi Nuno A. G. Graça Jan Voorberg
author_facet	Aicha Laghmouchi Nuno A. G. Graça Jan Voorberg
author_sort	Aicha Laghmouchi
title	Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura
title_short	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_sort	emerging concepts in immune thrombotic thrombocytopenic purpura
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/60f39ee536b34888bd6fb970198502b0
work_keys_str_mv	AT aichalaghmouchi emergingconceptsinimmunethromboticthrombocytopenicpurpura AT nunoaggraca emergingconceptsinimmunethromboticthrombocytopenicpurpura AT janvoorberg emergingconceptsinimmunethromboticthrombocytopenicpurpura
_version_	1718439492869685248

Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura

Ejemplares similares