Are Single Nucleotide Polymorphisms of the Immunoglobulin A Fc Receptor Gene Associated with Allergic Asthma?

Background: Eosinophils are important components of allergic inflammation. The immunoglobulin A (IgA) Fc receptor (FcαRI), encoded by the FCAR gene, is a possible candidate for eosinophil activation at mucosal surfaces, where IgA is abundant. Both elevated cell surface expression of FcαRI and increased avidity for IgA were described on eosinophils from allergic subjects. The aim of our study was to examine the possible association of FCAR gene polymorphisms with allergic asthma. Methods: We screened three regions of the FCAR gene: (1) the promoter region, (2) exon 3, encoding the first extracellular domain (EC1), and (3) exon 5, coding for the transmembrane and cytoplasmic domain, for new and published polymorphisms using a sensitive temperature gradient gel electrophoresis technique and compared their frequencies in 112 patients diagnosed with allergic asthma and 100 healthy controls. Results: Six polymorphisms, including two novel ones, were detected. No differences between patients and controls were found in the distribution of any of these polymorphisms. Conclusion: FcαRI polymorphism does not seem to be a risk factor in allergic asthma. Nevertheless, this is the first report on the distribution of 6 single nucleotide polymorphisms of the FCAR gene in a human population and the first study on FCAR polymorphism in allergic asthma.

[1]  M. Mańczak,et al.  A novel polymorphism in the cytoplasmic region of the human immunoglobulin A Fc receptor gene. , 2004, European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics.

[2]  A. Pawlik,et al.  The FcγRIIa Polymorphism in Children with Atopic Diseases , 2004, International Archives of Allergy and Immunology.

[3]  Wei Zhang,et al.  Crystal Structure of the Ectodomain of Human FcαRI* , 2003, Journal of Biological Chemistry.

[4]  P. Bjorkman,et al.  Insights into IgA-mediated immune responses from the crystal structures of human FcαRI and its complex with IgA1-Fc , 2003, Nature.

[5]  C. Ra,et al.  C/EBPα and Ets Protein Family Members Regulate the Human Myeloid IgA Fc Receptor (FcαR, CD89) Promoter1 , 2003, The Journal of Immunology.

[6]  C. Ober,et al.  Present status on the genetic studies of asthma. , 2002, Current opinion in immunology.

[7]  J. Leusen,et al.  Mac-1 (CD11b/CD18) as Accessory Molecule for FcαR (CD89) Binding of IgA1 , 2002, The Journal of Immunology.

[8]  S. Goto,et al.  Genetic polymorphisms in the promoter and 5′ UTR region of the Fc α receptor (CD89) are not associated with a risk of IgA nephropathy , 2001, Journal of Human Genetics.

[9]  P. Coffer,et al.  Cytokine-induced inside-out activation of FcalphaR (CD89) is mediated by a single serine residue (S263) in the intracellular domain of the receptor. , 2001, Blood.

[10]  Y. Tomino,et al.  Polymorphism in promoter region of Fcα receptor gene in patients with IgA nephropathy , 2001, Human Genetics.

[11]  C. Lay,et al.  The Interaction of FcαRI with IgA and Its Implications for Ligand Binding by Immunoreceptors of the Leukocyte Receptor Cluster1 , 2001, The Journal of Immunology.

[12]  P. Coffer,et al.  In vivo priming of FcαR functioning on eosinophils of allergic asthmatics , 2000, Journal of Leukocyte Biology.

[13]  C. Ra,et al.  Identification and characterization of the promoter for the gene encoding the human myeloid IgA Fc receptor (FcαR, CD89) , 2000, Immunogenetics.

[14]  R. Monteiro,et al.  Impaired expression of IgA Fc receptors (CD89) by blood phagocytic cells in ankylosing spondylitis. , 2000, Journal of Rheumatology.

[15]  P. Brandtzaeg,et al.  The B‐cell system of human mucosae and exocrine glands , 1999, Immunological reviews.

[16]  H. Kita,et al.  Does IgE bind to and activate eosinophils from patients with allergy? , 1999, Journal of immunology.

[17]  van Vuuren Aj,et al.  Characterization of the human myeloid IgA Fc receptor I (CD89) gene in a cosmid clone. , 1999 .

[18]  H. Kita,et al.  Interaction with secretory component stimulates effector functions of human eosinophils but not of neutrophils. , 1998, Journal of immunology.

[19]  D. Nahm,et al.  Elevation of specific immunoglobulin A antibodies to both allergen and bacterial antigen in induced sputum from asthmatics. , 1998, The European respiratory journal.

[20]  P. Robinson,et al.  Bipolar clamping improves the sensitivity of mutation detection by temperature gradient gel electrophoresis , 1998, Electrophoresis.

[21]  P. Jungers,et al.  Down-regulation of Fc alpha receptors on blood cells of IgA nephropathy patients: evidence for a negative regulatory role of serum IgA. , 1998, Kidney international.

[22]  L. Koenderman,et al.  Differential effects of the T helper cell type 2-derived cytokines IL-4 and IL-5 on ligand binding to IgG and IgA receptors expressed by human eosinophils. , 1997, Journal of immunology.

[23]  R. Pauwels,et al.  GLOBAL STRATEGY FOR ASTHMA MANAGEMENT AND PREVENTION , 1996 .

[24]  J. V. D. van de Winkel,et al.  Structure of the gene for the human myeloid IgA Fc receptor (CD89). , 1995, Journal of immunology.

[25]  A. Capron,et al.  Human eosinophils express a receptor for secretory component. Role in secretory IgA‐dependent activation , 1995, European journal of immunology.

[26]  M. Cooper,et al.  Definition of immunoglobulin A receptors on eosinophils and their enhanced expression in allergic individuals. , 1993, The Journal of clinical investigation.

[27]  G. Sutherland,et al.  The gene for the human IgA Fc receptor maps to 19q13.4 , 1992, Human Genetics.

[28]  C. March,et al.  Expression cloning of a human Fc receptor for IgA , 1990, The Journal of experimental medicine.

[29]  G. Gleich The eosinophil and bronchial asthma: current understanding. , 1990, The Journal of allergy and clinical immunology.

[30]  R. Kyle,et al.  IgA-induced eosinophil degranulation. , 1989, Journal of immunology.

[31]  G. Canonica,et al.  Antiallergic drugs and the immune response , 1989, Allergy.

[32]  J. G. Winkel,et al.  Alternatively spliced forms of the human myeloid Fcα receptor (CD89) in neutrophils , 2004, Immunogenetics.

[33]  R. Monteiro,et al.  IgA Fc receptors. , 2003, Annual review of immunology.

[34]  J. V. D. van de Winkel,et al.  Characterization of the human myeloid IgA Fc receptor I (CD89) gene in a cosmid clone , 1999, Immunogenetics.

[35]  J. Bousquet,et al.  Skin tests used in type I allergy testing Position paper. Sub-Committee on Skin Tests of the European Academy of Allergology and Clinical Immunology. , 1989, Allergy.