title: Dysgammaglobulinemia Associated With Glu349del, a Hypomorphic XIAP Mutation.
abstract: BACKGROUND
  X-linked lymphoproliferative syndrome type 2 is a rare hereditary immunodeficiency caused by mutations in the XIAP gene. This immunodeficiency frequently results in hemophagocytic lymphohistiocytosis, although hypogammaglobulinemia and dysgammaglobulinemia are also common.
  
  
  OBJECTIVE
  We identified 17 patients from 12 Japanese families with mutations in XIAP. The Glu349del mutation was observed in 3 patients, each from a different family. Interestingly, these patients exhibited dysgammaglobulinemia but not hemophagocytic lymphohistiocytosis. We conducted an immunological study of patients carrying Glu349del and other mutations to elucidate the pathogenic mechanisms of dysgammaglobulinemia in patients with mutations in the XIAP gene.
  
  
  METHODS
  We performed an immunological study of 2 patients carrying the Glu349del mutation and 8 patients with other mutations.
  
  
  RESULTS
  Flow cytometry showed that the percentage of memory B cells in patients with a mutation in XIAP was lower than that observed in the healthy controls. The patients with the Glu349del mutation had a lower percentage of memory B cells than those with other mutations. Ig production was reduced in patients with the Glu349del mutation. Increased susceptibility to apoptosis was observed in the patients with other mutations. Susceptibility to apoptosis was normal in patients with Glu349del. Microarray analysis indicated that expression of Ig-related genes was reduced in patients with the Glu349del mutation and that the pattern was different from that observed in the healthy controls or patients with other mutations in XIAP.
  
  
  CONCLUSIONS
  Patients carrying the Glu349del mutation in the XIAP gene may have a clinically and immunologically distinct phenotype from patients with other XIAP mutations. The Glu349del mutation may be associated with dysgammaglobulinemia.
authors.forename: N
authors.initials: N
authors.lastname: Nishida
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: I
authors.initials: I
authors.lastname: Takasaki
authors.forename: K
authors.initials: K
authors.lastname: Imai
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Imamura
authors.forename: R
authors.initials: R
authors.lastname: Miyashita
authors.forename: F
authors.initials: F
authors.lastname: Kato
authors.forename: A
authors.initials: A
authors.lastname: Yamaide
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: J
authors.initials: J
authors.lastname: Hara
authors.forename: Y
authors.initials: Y
authors.lastname: Adachi
authors.forename: T
authors.initials: T
authors.lastname: Miyawaki
authors.forename: H
authors.initials: H
authors.lastname: Kanegane
mesh_terms: D000293:Adolescent; D017209:Apoptosis; D044466:Asian People / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004406:Dysgammaglobulinemia / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping / Q000379:methods; D007223:Infant; D007564:Japan; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*
chemical_list: D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human