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Genetic markers and danger signals in stevens-johnson syndrome and toxic epidermal necrolysis.
MedLine Citation:
PMID:  20962567     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse reactions, which could be induced by a variety of drugs. It was proposed that human leukocyte antigen (HLA)-restricted presentation of antigens (drugs or their metabolites) to T lymphocytes initiates the immune reactions of SJS/TEN. However, the genetic susceptibility and the exact pathogenesis were not clear until the recent studies. We first identified that HLA-B*1502 is strongly associated with carbamazepine (CBZ)-induced SJS/TEN and HLA-B*5801 with allopurinol-SJS/TEN in Han Chinese. The same associations had been validated across different human populations. For the downstream danger signals, Fas-Fas ligand (FasL) and perforin/granzyme B had been advocated as cytotoxic mediators for keratinocyte death in SJS/TEN. However, expression levels of these cytotoxic proteins from the skin lesions were too low to explain the distinct and extensive epidermal necrosis. Our recent study identified that the granulysin, a cytotoxic protein released from cytotoxic T cells or natural killer (NK) cells, is a key mediator for disseminated keratinocyte death in SJS/TEN. This article aims to provide an overview of both of the genomic and immunologic perspectives of SJS/TEN. These studies give us a better understanding of the immune mechanisms, biomarkers for disease prevention and early diagnosis, as well as providing the therapeutic targets for the treatments of SJS/TEN.
Authors:
Wen-Hung Chung; Shuen-Iu Hung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-25
Journal Detail:
Title:  Allergology international : official journal of the Japanese Society of Allergology     Volume:  59     ISSN:  1440-1592     ISO Abbreviation:  Allergol Int     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9616296     Medline TA:  Allergol Int     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  325-32     Citation Subset:  IM    
Affiliation:
Department of Dermatology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan. chung1@cgmh.org.tw
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