title: Persistent hypogammaglobulinemia following mononucleosis in boys is highly suggestive of X-linked lymphoproliferative disease--report of three cases.
abstract: Hypogammaglobulinemia is a common symptom in different immunodeficiencies. It is, however, not usually associated with Epstein-Barr virus (EBV) infections. The X-linked lymphoproliferative disease (XLP) on the other hand shows immunological changes in response to the EBV. Here we report three previously healthy boys, all of which developed persistent hypogammaglobulinemia following severe acute infectious mononucleosis. All three patients revealed T-cell abnormalities including inverted CD4/CD8 and increased CD8(+) T-cell numbers. The number of IFN-gamma-producing T cells were markedly increased in the two patients studied so far. In addition, patient 2 showed mainly T cells, instead of B cells, to be infected with the EBV. Apart from an uncle of patient 3, who died of malignant lymphoma, family history was unremarkable in all cases. All three patients exhibited mutations in the SH2D1A gene, establishing the diagnosis of XLP. Protein expression was found on immunoblot analysis in one patient with a missense mutation. Development of persistent hypogammaglobulinemia after severe primary EBV infection seems to be a specific diagnostic sign for XLP even in males with unremarkable family history.
authors.affiliation: Hospital for Children and Adolescents, University of Leipzig, 04317 Leipzig, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Hügle
authors.forename: P
authors.initials: P
authors.lastname: Suchowerskyj
authors.forename: H
authors.initials: H
authors.lastname: Hellebrand
authors.forename: B
authors.initials: B
authors.lastname: Adler
authors.forename: M
authors.initials: M
authors.lastname: Borte
authors.forename: U
authors.initials: U
authors.lastname: Sack
authors.forename: U Schulte
authors.initials: US
authors.lastname: Overberg-Schmidt
authors.forename: N
authors.initials: N
authors.lastname: Strnad
authors.forename: J
authors.initials: J
authors.lastname: Otto
authors.forename: A
authors.initials: A
authors.lastname: Meindl
authors.forename: V
authors.initials: V
authors.lastname: Schuster
mesh_terms: D000361:Agammaglobulinemia / Q000276:immunology*; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D040181:Genetic Diseases, X-Linked / Q000276:immunology*; D006801:Humans; D007223:Infant; D007244:Infectious Mononucleosis / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D008297:Male; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein