Hemophagocytic lymphohistiocytosis due to germline mutations in SH2D1A, the X-linked lymphoproliferative disease gene

M. Arico, S. Imashuku, R. Clementi, S. Hibi, T. Teramura, C. Danesino, D. A. Haber, K. E. Nichols

Research output: Contribution to journalArticle

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Abstract

The hemophagocytic lymphohistiocytoses (HLH) comprise a heterogeneous group of disorders characterized by dysregulated activation of T cells and macrophages. Although some patients with HLH harbor perforin gene mutations, the cause of the remaining cases is not known. The phenotype of HLH bears a strong resemblance to X-linked lymphoproliferative disease (XLP), an Epstein-Barr virus (EBV)-associated immunodeficiency resulting from defects in SH2D1A, a small SH2 domain-containing protein expressed in T lymphocytes and natural killer cells. Here it is shown that 4 of 25 male patients with HLH who were examined harbored germline SH2D1A mutations. Among these 4 patients, only 2 had family histories consistent with XLP. On the basis of these findings, it is suggested that all male patients with EBV-associated hemophagocytosis be screened for mutations in SH2D1A. Patients identified as having XLP should undergo genetic counseling, and be followed long-term for development of lymphoma and hypogammaglobulinemia.

Original languageEnglish
Pages (from-to)1131-1133
Number of pages3
JournalBlood
Volume97
Issue number4
DOIs
Publication statusPublished - Feb 15 2001

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Hemophagocytic Lymphohistiocytosis
Lymphoproliferative Disorders
Germ-Line Mutation
T-cells
Genes
Viruses
Perforin
Human Herpesvirus 4
Macrophages
Ports and harbors
T-Lymphocytes
Agammaglobulinemia
Chemical activation
Mutation
src Homology Domains
Genetic Counseling
Defects
Natural Killer Cells
Lymphoma
Proteins

ASJC Scopus subject areas

  • Hematology

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Hemophagocytic lymphohistiocytosis due to germline mutations in SH2D1A, the X-linked lymphoproliferative disease gene. / Arico, M.; Imashuku, S.; Clementi, R.; Hibi, S.; Teramura, T.; Danesino, C.; Haber, D. A.; Nichols, K. E.

In: Blood, Vol. 97, No. 4, 15.02.2001, p. 1131-1133.

Research output: Contribution to journalArticle

Arico, M, Imashuku, S, Clementi, R, Hibi, S, Teramura, T, Danesino, C, Haber, DA & Nichols, KE 2001, 'Hemophagocytic lymphohistiocytosis due to germline mutations in SH2D1A, the X-linked lymphoproliferative disease gene', Blood, vol. 97, no. 4, pp. 1131-1133. https://doi.org/10.1182/blood.V97.4.1131
Arico, M. ; Imashuku, S. ; Clementi, R. ; Hibi, S. ; Teramura, T. ; Danesino, C. ; Haber, D. A. ; Nichols, K. E. / Hemophagocytic lymphohistiocytosis due to germline mutations in SH2D1A, the X-linked lymphoproliferative disease gene. In: Blood. 2001 ; Vol. 97, No. 4. pp. 1131-1133.
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