RGD Reference Report - A novel splice variant of FcgammaRIIa: a risk factor for anaphylaxis in patients with hypogammaglobulinemia. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

A novel splice variant of FcgammaRIIa: a risk factor for anaphylaxis in patients with hypogammaglobulinemia.

Authors: Van der Heijden, J  Geissler, J  Van Mirre, E  Van Deuren, M  Van der Meer, JW  Salama, A  Van den Berg, TK  Roos, D  Kuijpers, TW 
Citation: van der Heijden J, etal., J Allergy Clin Immunol. 2013 May;131(5):1408-16.e5. doi: 10.1016/j.jaci.2013.02.009. Epub 2013 Mar 29.
RGD ID: 11040993
Pubmed: PMID:23545275   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jaci.2013.02.009   (Journal Full-text)

BACKGROUND: Our index case was a patient with common variable immunodeficiency (CVID). She had anaphylactoid reactions on administration of intravenous immunoglobulin (IVIg) associated with the presence of IgG antibodies against IgA. OBJECTIVE: We sought to determine the role of Fcgamma receptor (FcgammaR) IIa in IVIg-induced anaphylactoid reactions. METHODS: Neutrophils and PBMCs were isolated from healthy subjects and IVIg-treated patients. FcgammaRIIa mRNA and DNA were analyzed by using real-time PCR and sequencing. IgG-mediated elastase release and intracellular Ca(2+) mobilization were determined in neutrophils and transfected cell lines, respectively. RESULTS: A novel splice variant of FcgammaRIIa containing an expressed cryptic exon 6* (FcgammaRIIa(exon6 *)) was identified in our index patient. This exon is normally spliced out of all FcgammaRII isoforms, except the inhibitory FcgammaRIIb1. Compared with healthy control subjects, the heterozygous FCGR2A(c.742+871A>G) mutation was more frequent in patients with CVID (n = 53, P < .013). Expression in patients with CVID was associated with anaphylaxis on IVIg infusion (P = .002). On screening of additional IVIg-treated patient cohorts, we identified 6 FCGR2A(c.742+871A>G) allele-positive patients with Kawasaki disease (n = 208) and 1 patient with idiopathic thrombocytopenia (n = 93). None had adverse reactions to IVIg. Moreover, FcgammaRIIa(exon6 *) was also demonstrated in asymptomatic family members. Functional studies in primary cells and transfected murine cells demonstrated enhanced cellular activation by FcgammaRIIa(exon6 *) compared with its native form, as shown by increased elastase release and intracellular calcium mobilization. CONCLUSION: A novel splice variant, FcgammaRIIa(exon6 *), was characterized as a low-frequency allele, coding for a gain-of-function receptor for IgG. In the presence of immune complexes, FcgammaRIIa(exon6 *) can contribute to anaphylaxis in patients with CVID.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FCGR2AHumanAnaphylaxis susceptibilityIAGP associated with Agammaglobulinemia and DNA:mutation:splice junction:RGD 
Fcgr2aRatAnaphylaxis susceptibilityISOFCGR2A (Homo sapiens)associated with Agammaglobulinemia and DNA:mutation:splice junction:RGD 
Fcgr3MouseAnaphylaxis susceptibilityISOFCGR2A (Homo sapiens)associated with Agammaglobulinemia and DNA:mutation:splice junction:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fcgr2a  (Fc gamma receptor 2A)

Genes (Mus musculus)
Fcgr3  (Fc receptor, IgG, low affinity III)

Genes (Homo sapiens)
FCGR2A  (Fc gamma receptor IIa)


Additional Information