| Affiliation: | (1) Istituto di Medicina Molecolare “Angelo Nocivelli,”, Clinica Pediatrica, Università di Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy;(2) Division of Rheumatology and Clinical Immunology, Medical School, University of Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany;(3) Istituto di Medicina Molecolare “Angelo Nocivelli,”, Clinica Pediatrica, Università di Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy |
| Abstract: | 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. |
