Mutational Analysis of Human BLyS in Patients with Common Variable Immunodeficiency
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BLyS, a TNF family member, is crucial for B cell proliferation and differentiation by acting through its three receptors, TACI, BCMA and BAFF-R. The knock out model for BLyS is characterized by an immunological phenotype reminiscent of the human phenotype of common variable immunodeficiency (CVID). CVID is characterized by a defective B cell compartment, evidencing the putative importance of BLyS in its pathogenesis. On the contrary, the transgenic model for BLys is characterized by autoimmune manifestations, underlying its role in B cell regulation. In fact, mutations in TACI, one of the three BLyS receptors, are associated with CVID. Based on these facts, we hypothesized that BLyS could be a candidate gene for CVID. We screened 78 patients with CVID using DHPLC and direct sequencing: No disease causing mutations were identified. A novel heterozygous single nucleotide polymorphism (SNP) was found in exon 1 of one individual, however this SNP (G189A) does not lead to an amino acid substitution.
KEY WORDS:TNF family BAFF BLyS B cell differentiation CVID Polymorphic variants Mutational analysis DHPLC
We would like to thank the referring physicians for their collaboration, Mrs. Jessica Pfannstiel and Mrs. Giovanna Falsetti for excellent technical assistance. This work was partly supported by the Center for Primary Immunodeficiencies “Mario Di Martino” and Camillo Golgi Foundation, Brescia. B.G. and U.S. were supported by grants of the Deutsche Forschungsgemeinschaft (DFG) GR1617/3 and SFB620/C2, and a USIDnet grant NO1-A1-30070. Both groups were supported by EU Contract No. SP23-CT-2005-006411, EURO-POLICY-PID.
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