دورية
Relevance of biallelic versus monoallelic TNFRSF13Bmutations in distinguishing disease-causing from risk-increasing TNFRSF13Bvariants in antibody deficiency syndromes
| العنوان: | Relevance of biallelic versus monoallelic TNFRSF13Bmutations in distinguishing disease-causing from risk-increasing TNFRSF13Bvariants in antibody deficiency syndromes |
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| المؤلفون: | Salzer, Ulrich, Bacchelli, Chiara, Buckridge, Sylvie, Pan-Hammarström, Qiang, Jennings, Stephanie, Lougaris, Vassilis, Bergbreiter, Astrid, Hagena, Tina, Birmelin, Jennifer, Plebani, Alessandro, Webster, A. David B., Peter, Hans-Hartmut, Suez, Daniel, Chapel, Helen, McLean-Tooke, Andrew, Spickett, Gavin P., Anover-Sombke, Stephanie, Ochs, Hans D., Urschel, Simon, Belohradsky, Bernd H., Ugrinovic, Sanja, Kumararatne, Dinakantha S., Lawrence, Tatiana C., Holm, Are M., Franco, Jose L., Schulze, Ilka, Schneider, Pascal, Gertz, E. Michael, Schäffer, Alejandro A., Hammarström, Lennart, Thrasher, Adrian J., Gaspar, H. Bobby, Grimbacher, Bodo |
| المصدر: | Blood; February 2009, Vol. 113 Issue: 9 p1967-1976, 10p |
| مستخلص: | TNFRSF13Bencodes transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), a B cell– specific tumor necrosis factor (TNF) receptor superfamily member. Both biallelic and monoallelic TNFRSF13Bmutations were identified in patients with common variable immunodeficiency disorders. The genetic complexity and variable clinical presentation of TACI deficiency prompted us to evaluate the genetic, immunologic, and clinical condition in 50 individuals with TNFRSF13Balterations, following screening of 564 unrelated patients with hypogammaglobulinemia. We identified 13 new sequence variants. The most frequent TNFRSF13Bvariants (C104R and A181E; n = 39; 6.9%) were also present in a heterozygous state in 2% of 675 controls. All patients with biallelic mutations had hypogammaglobulinemia and nearly all showed impaired binding to a proliferation-inducing ligand (APRIL). However, the majority (n = 41; 82%) of the pa-tients carried monoallelic changes in TNFRSF13B. Presence of a heterozygous mutation was associated with antibody deficiency (P<.001, relative risk 3.6). Heterozygosity for the most common mutation, C104R, was associated with disease (P< .001, relative risk 4.2). Furthermore, heterozygosity for C104R was associated with low numbers of IgD−CD27+B cells (P= .019), benign lymphoproliferation (P< .001), and autoimmune complications (P= .001). These associations indicate that C104R heterozygosity increases the risk for common variable immunodeficiency disorders and influences clinical presentation. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00064971 15280020 |
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| DOI: | 10.1182/blood-2008-02-141937 |