Restricted accessCase reportFirst published online 2015-06
A Boy Aged 5 Years 10 Months with IgM Deficiency and Antibody Deficiency to Streptococcus pneumoniae Associated with TNFRSF13B C104R Heterozygous Mutation
The case is presented of a boy aged 5 years and 10 months with recurrent infections and intermittent thrombocytopenia who had immunoglobulin M (IgM) deficiency and specific antibody deficiency to Streptococcus pneumoniae. Whole exome sequencing was performed and revealed a transmembrane activator and calcium modulator and cyclophilin ligand interactor gene mutation, which has been seen in common variable immunodeficiency. He was treated with IgG antibody replacement therapy and has been free of infection with resolution of his thrombocytopenia.
Get full access to this article
View all access options for this article.
References
1.
LeivaLE, MonjureH, SorensenRU. Recurrent respiratory infections, specific antibody deficiencies, and memory B cells. J Clin Immunol, 2013; 33:S57–61.
2.
BoyleRJ, LeC, BallochA, TangML-K. The clinical syndrome of specific antibody deficiency in children. Clin Exp Immunol, 2006; 146:486–492.
3.
WolpertJ, KnutsenAP. Natural history of selective antibody deficiency to bacterial polysaccharide antigens in children. Pediatr Asthma Allergy Immunol, 1998; 12:183–191.
4.
ResnickES, MoshierEL, GodboldJH, Cunningham-RundlesC. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood, 2012; 119:1650–1657.
5.
SalzerU, ChapelH, WebsterA, et al.Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nature Genetics, 2005; 37:820–828.
6.
Martinez-Gallo, RadiganL, AlmejúnMB, Martínez-PomarN, MatamorosN, Cunningham-RundlesC. TACI mutations and impaired B-cell function in subjects with CVID and healthy heterozygotes. J Allergy Clin Immunol, 2013; 131:468–476.
7.
SalzerU, BacchelliC, BuckridgeS, et al.Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes. Blood, 2009; 113:1967–1976.
8.
FreibergerT, RavčukovaB, GrodeckaL, et al.Sequence variants of the TNFRSF13B gene in Czech CVID and IgAD patients in the context of other populations. Human Immunol, 2012; 73:1147–1154.
LeeJJ, JabaraHH, GaribyanL, et al.The C104R mutant impairs the function of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) through haploinsufficiency. J Allergy Clin Immunol, 2010; 126:1234–1241.
11.
GaribyanL, LobitoAA, SiegelRM, CallME, WucherpfennigKW, GehaRS. Dominant-negative effect of the heterozygous C104R TACI mutation in common variable immunodeficiency (CVID). J Clin Immunol, 2007; 117:1550–1557.
12.
ChouJ, OhsumiT, GehaR. Use of whole exome and genome sequencing in the identification of genetic causes of primary immunodeficiencies. Curr Opin Allergy Clin Immunol, 2012; 12:623–628.
13.
ShearerWT, RosenblattHM, GelmanRS, et al.Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol, 2003; 112:973–980.
