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Pemphigus autoimmunity: Hypotheses and realities
The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Eluci...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Informa Healthcare
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251002/ https://www.ncbi.nlm.nih.gov/pubmed/21939410 http://dx.doi.org/10.3109/08916934.2011.606444 |
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author | Grando, Sergei A |
author_facet | Grando, Sergei A |
author_sort | Grando, Sergei A |
collection | PubMed |
description | The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients. |
format | Online Article Text |
id | pubmed-3251002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Informa Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-32510022012-01-11 Pemphigus autoimmunity: Hypotheses and realities Grando, Sergei A Autoimmunity Article The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients. Informa Healthcare 2011-02 2011-09-23 /pmc/articles/PMC3251002/ /pubmed/21939410 http://dx.doi.org/10.3109/08916934.2011.606444 Text en © Informa UK, Ltd http://creativecommons.org/licenses/by/2.0/ This is an open access article distributed under the Supplemental Terms and Conditions for iOpenAccess articles published in Informa Healthcare journals (http://www.informaworld.com/mpp/uploads/iopenaccess_tcs.pdf) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Grando, Sergei A Pemphigus autoimmunity: Hypotheses and realities |
title | Pemphigus autoimmunity: Hypotheses and realities |
title_full | Pemphigus autoimmunity: Hypotheses and realities |
title_fullStr | Pemphigus autoimmunity: Hypotheses and realities |
title_full_unstemmed | Pemphigus autoimmunity: Hypotheses and realities |
title_short | Pemphigus autoimmunity: Hypotheses and realities |
title_sort | pemphigus autoimmunity: hypotheses and realities |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251002/ https://www.ncbi.nlm.nih.gov/pubmed/21939410 http://dx.doi.org/10.3109/08916934.2011.606444 |
work_keys_str_mv | AT grandosergeia pemphigusautoimmunityhypothesesandrealities |