Abstract
BackgroundAutoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC. We examined single-nucleotide polymorphism (SNPs) in the CD16A and CD32 genes in patients with MD which may determine a Fcγ receptor with lower binding to CIC.MethodsThe functional CD16A (FcγRIIIa*559A > C, rs396991) and CD32A (FcγRIIa*519A > G, rs1801274) SNPs were analyzed using PCR-based TaqMan Genotyping Assay in two cohorts of 156 mediterranean and 112 Galicia patients in a case-control study. Data were analyzed by χ2 with Fisher's exact test and Cochran-Armitage trend test (CATT). CIC were measured by ELISA for C1q-binding CIC.ResultsElevated CIC were found in 7% of patients with MD during the intercrisis period. No differences were found in the allelic frequency for rs396991 or rs1801274 in controls subjects when they were compared with patients with MD from the same geographic area. However, the frequency of AA and AC genotypes of CD16A (rs396991) differed among mediterranean and Galicia controls (Fisher's test, corrected p = 6.9 × 10-4 for AA; corrected p = 0.02 for AC). Although genotype AC of the CD16A receptor was significantly more frequent in mediterranean controls than in patients, [Fisher's test corrected p = 0.02; OR = 0.63 (0.44-0.91)], a genetic additive effect for the allele C was not observed (CATT, p = 0.23). Moreover, no differences were found in genotype frequencies for rs396991 between patients with MD and controls from Galicia (CATT, p = 0.14). The allelic frequency of CD32 (rs1801274) was not different between patients and controls either in mediterranean (p = 0.51) or Galicia population (p = 0.11).ConclusionsElevated CIC are not found in most of patients with MD. Functional polymorphisms of CD16A and CD32 genes are not associated with onset of MD.
Highlights
Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease
The CD32 (FcgRIIa*519A > G) and CD16A (FcgRIIIa*559A > C) single-nucleotide polymorphism (SNPs) in the Fcg receptors were selected to investigate their association with Ménière’s disease (MD)
Genotype distributions of both SNPs in mediterranean and Galicia controls exhibited Hardy- Weinberg equilibrium, and the minor allele frequencies of all SNPs were over 5% in controls from both groups
Summary
Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcg receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière’s disease (MD) could be mediated by an immune response driven by CIC. We examined single-nucleotide polymorphism (SNPs) in the CD16A and CD32 genes in patients with MD which may determine a Fcg receptor with lower binding to CIC. The response to steroids therapy and the finding of elevated levels of circulating immune complexes (CIC) in some patients with MD, especially in the active phase, has supported the hypothesis of autoimmunity in MD [15,16]. The Fcg receptors CD16A and CD32A connect the innate and the adaptative immune response by transmitting activating signals to natural killer lymphocytes and myeloid cell upon recognition of Fc of IgG [17] A decrease in CIC clearance could determine an increase of CIC levels which are deposited in the blood vessels of the endolymphatic sac, resulting in inflammation with increase in vascular permeability and the development of endolymphatic hydrops [16].
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