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. PATIENTS AND 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.
Subject(s)
Dysgammaglobulinemia/genetics , Genetic Diseases, X-Linked/genetics , Lymphoproliferative Disorders/genetics , Mutation , X-Linked Inhibitor of Apoptosis Protein/genetics , Adolescent , Apoptosis , Asian People/genetics , B-Lymphocytes/immunology , Case-Control Studies , Cells, Cultured , Child , Child, Preschool , DNA Mutational Analysis , Dysgammaglobulinemia/diagnosis , Dysgammaglobulinemia/ethnology , Dysgammaglobulinemia/immunology , Female , Flow Cytometry , Gene Expression Profiling/methods , Genetic Diseases, X-Linked/diagnosis , Genetic Diseases, X-Linked/ethnology , Genetic Diseases, X-Linked/immunology , Genetic Predisposition to Disease , Humans , Immunologic Memory , Immunophenotyping/methods , Infant , Japan , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/ethnology , Lymphoproliferative Disorders/immunology , Male , Oligonucleotide Array Sequence Analysis , Pedigree , Phenotype , T-Lymphocytes/immunology , T-Lymphocytes/pathologyABSTRACT
The frequency of selective IgA deficiency (SIgAD) was determined in 33,171 Chinese distributed in six nationalities by Ouchterlony's double diffusion with 5 mg/dl as the limit of detection. Those who were found IgA-deficient were retested by single radial diffusion technique. Gel diffusion analysis of sera revealed apparent lack of IgA in 8 samples, all with normal levels of IgG and IgM (age-matched). The incidence was 0.024% (1:4,100). The incidences among the six nationalities were Han 1:2,600, Hui 1:5,000, Mongolia 1:2,700, Tujia 1:4,300, Zhuang 0:5,300, and Bai 1:4,800. All of the individuals, who had low levels of IgA or no IgA detectable, were below 16 years of age. Of these, 2 sera were autoantibody (anti-smooth muscle antibody) positive Delayed hypersensitivity skin tests were negative in one individual. The chief clinical manifestations were those of respiratory tract infections, of which about 50% were in subclinical state.
Subject(s)
Dysgammaglobulinemia/epidemiology , IgA Deficiency/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , China/epidemiology , Dysgammaglobulinemia/ethnology , Ethnicity , Female , Humans , IgA Deficiency/ethnology , Infant , Male , Middle Aged , PrevalenceABSTRACT
Serum IgA concentrations were measured in 1799 healthy Israeli military recruits (698 women and 1101 men) using an automated nephelometric system. The overall prevalence of IgA deficiency defined at a level of less than 50 mg/liter was 1.0 +/- 0.46% (95% confidence limits). No significant difference was found between the sexes in the mean values of serum IgA. Statistically significant ethnic differences were evident. Recruits of European origin had lower serum IgA concentrations than the North African, Israeli, or Asian origin groups. Whether the apparently high prevalence of IgA deficiency in this young population in Israel has clinical significance is at present unknown.
