PMID- 20962567
OWN - NLM
STAT- MEDLINE
DCOM- 20110718
LR  - 20151119
IS  - 1440-1592 (Electronic)
IS  - 1323-8930 (Linking)
VI  - 59
IP  - 4
DP  - 2010 Dec
TI  - Genetic markers and danger signals in stevens-johnson syndrome and toxic 
      epidermal necrolysis.
PG  - 325-32
LID - 10.2332/allergolint.10-RAI-0261 [doi]
AB  - 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.
FAU - Chung, Wen-Hung
AU  - Chung WH
AD  - Department of Dermatology, Chang Gung Memorial Hospital, Chang Gung University, 
      Taipei, Taiwan. chung1@cgmh.org.tw
FAU - Hung, Shuen-Iu
AU  - Hung SI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20101025
PL  - England
TA  - Allergol Int
JT  - Allergology international : official journal of the Japanese Society of 
      Allergology
JID - 9616296
RN  - 0 (Biomarkers)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*15:02 antigen)
RN  - 0 (HLA-B15 Antigen)
RN  - 33CM23913M (Carbamazepine)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - Allopurinol/adverse effects
MH  - Apoptosis/genetics/immunology
MH  - Biomarkers/*metabolism
MH  - Carbamazepine/adverse effects
MH  - Cytotoxicity, Immunologic/genetics
MH  - Genetic Predisposition to Disease
MH  - Granzymes/immunology/metabolism
MH  - HLA-B Antigens/genetics/metabolism
MH  - HLA-B15 Antigen
MH  - Humans
MH  - Keratinocytes/*immunology
MH  - Killer Cells, Natural/immunology
MH  - Polymorphism, Genetic
MH  - Stevens-Johnson Syndrome/chemically induced/etiology/genetics/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2010/10/22 06:00
MHDA- 2011/07/19 06:00
CRDT- 2010/10/22 06:00
PHST- 2010/08/31 00:00 [received]
PHST- 2010/10/22 06:00 [entrez]
PHST- 2010/10/22 06:00 [pubmed]
PHST- 2011/07/19 06:00 [medline]
AID - S1323-8930(15)30643-2 [pii]
AID - 10.2332/allergolint.10-RAI-0261 [doi]
PST - ppublish
SO  - Allergol Int. 2010 Dec;59(4):325-32. doi: 10.2332/allergolint.10-RAI-0261. Epub 
      2010 Oct 25.