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Erschienen in: Journal of Clinical Immunology 6/2009

01.11.2009

Novel Mutations in TACI (TNFRSF13B) Causing Common Variable Immunodeficiency

verfasst von: Javad Mohammadi, Chonghai Liu, Asghar Aghamohammadi, Astrid Bergbreiter, Likun Du, Jiayi Lu, Nima Rezaei, Ali Akbar Amirzargar, Mostafa Moin, Ulrich Salzer, Qiang Pan-Hammarström, Lennart Hammarström

Erschienen in: Journal of Clinical Immunology | Ausgabe 6/2009

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Abstract

Introduction

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production. The disorder is also characterized by co-occurrence of autoimmune, lymphoproliferative, and granulomatous diseases. Mutations in the gene encoding TACI (Transmembrane Activator and CAML Interactor, TNFRSF13B) were previously found to be associated with CVID.

Materials and Methods

We therefore sequenced TNFRSF13B gene in a cohort of 48 Iranian CVID patients. Expression of TACI and binding of A proliferation-inducing ligand (APRIL) were tested by FACS.

Results

We identified one patient with a homozygous G to T substitution in the TNFRSF13B gene at the splice site of intron 1 (c.61+1G>T), which abolished expression of the TACI molecule and binding capacity of APRIL. This represents the second CVID patient in the world with a complete absence of TACI expression. B cell lines from family members carrying the same mutation in a heterozygous form showed a reduced level of TACI expression and APRIL-binding capacity, suggesting a gene dosage effect. In addition, we found the previously recognized C104R and C172Y mutations in a heterozygous form in two patients with CVID and one, novel, heterozygous P42T mutation.

Conclusion

TACI mutations were observed in Iran CVID patients in a similar frequency as in other Caucasian populations. The novel mutations identified in this study support the notion of a crucial role for TACI in B cell differentiation.
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Metadaten
Titel
Novel Mutations in TACI (TNFRSF13B) Causing Common Variable Immunodeficiency
verfasst von
Javad Mohammadi
Chonghai Liu
Asghar Aghamohammadi
Astrid Bergbreiter
Likun Du
Jiayi Lu
Nima Rezaei
Ali Akbar Amirzargar
Mostafa Moin
Ulrich Salzer
Qiang Pan-Hammarström
Lennart Hammarström
Publikationsdatum
01.11.2009
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 6/2009
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-009-9317-5

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