title: Sequence analysis of TNFRSF13b, encoding TACI, in patients with systemic lupus erythematosus.
abstract: B cell activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL), and their receptors BAFF receptor (BAFFR), B cell maturation antigen (BCMA), and transmembrane activator and CAML interactor (TACI) are involved in the regulation of B cell homeostasis and differentiation. BAFF overexpression leads to systemic lupus erythematosus (SLE) in mice and elevated BAFF levels have been observed in human SLE and mouse models for SLE. Furthermore, genetic inactivation of TACI in mice results in a SLE-like phenotype. Based on our recent finding that TACI is mutated in patients with common variable immunodeficiency, of whom more than 30% suffer from autoimmune conditions, we analyzed TACI in humans with SLE. Sequence analysis of TNFRSF13b/TACI in 119 unrelated SLE patients revealed four variants: R20C in exon 1, R72H in exon 3, the silent variation c.327 G > A in exon 3, and A181E in exon 4. No significant association with any of these variants was found, when compared to the frequencies of the variants in a healthy control cohort. Furthermore, the mutated alleles R20C and R72H did not segregate with the SLE phenotype in familial cases of SLE. Thus, our evaluation of the coding region of TNFRSF13b/TACI did not reveal any deleterious or disease-associated mutations.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Salzer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Birmelin
authors.forename: Chiara
authors.initials: C
authors.lastname: Bacchelli
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.forename: Ulrike
authors.initials: U
authors.lastname: Buchegger-Podbielski
authors.forename: Sylvie
authors.initials: S
authors.lastname: Buckridge
authors.forename: Rita
authors.initials: R
authors.lastname: Rzepka
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.forename: Inga
authors.initials: I
authors.lastname: Melchers
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
mesh_terms: D001483:Base Sequence; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D017421:Sequence Analysis; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics*
chemical_list: C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein