High frequency of QPY allele and linkage disequilibrium of granzyme-B in Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis.
Mediation of Epstein-Barr virus (EBV)-specific cytotoxicity in T lymphocyte via the perforin/granzyme pathway has been demonstrated; therefore, a study involving cytolytic molecules was essential for the clarification of hemophagocytic lymphohistiocytosis (HLH) pathogenesis. This investigation, which analysed the frequency of three allelic mutations of granzyme-B (55Q/R, 95P/A and 247Y/H) in patients with EBV-HLH and infectious mononucleosis, identified the high prevalence of the QPY haplotype in EBV-HLH patients in comparison with healthy controls. A > G polymorphism was also detected in intron 5; furthermore, nearly complete linkage disequilibrium was observed among these polymorphisms. The recessive role of the QPY haplotype of granzyme-B might be responsible for the pathogenesis of EBV-HLH. Cytotoxicity and DNA fragmentation of cytotoxic T lymphocytes did not differ among patients characterized by the QPY/QPY, RAH/RAH and QPY/RAH genotypes. This finding suggested that DNA fragmentation in target cells is mediated not only by granzyme-B but also by other molecules, including other granzymes or Fas.
Zaitsu
M
M
Department of Pediatrics, Saga University, Saga, Japan.
Yamamoto
K
K
Ishii
E
E
Teramura
T
T
Nakadate
N
N
Sako
M
M
Sakata
N
N
Wakiguchi
H
H
Hirose
M
M
Imayoshi
M
M
Ogata
Y
Y
Imashuku
S
S
Hamasaki
Y
Y
Yasukawa
M
M
D020022:Genetic Predisposition to Disease; D053804:Granzymes; D004854:Herpesvirus 4, Human / Q000378:metabolism; D015616:Histiocytosis, Non-Langerhans-Cell / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015810:Linkage Disequilibrium; D017354:Point Mutation; D012697:Serine Endopeptidases / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases