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.

Gleich GJ: The eosinophil and bronchial asthma: Current understanding. J Allergy Clin Immunol 1990;85:422–446.
Brandtzaeg P, Farstad IN, Johansen FE, Morton HC, Norderhaug IN, Yamanaka T: The B cell system of human mucosae and exocrine glands. Immunol Rev 1999;171:45–87.
Nahm DH, Kim HY, Park HS: Elevation of specific immunoglobulin A antibodies to both allergen and bacterial antigen in induced sputum from asthmatics. Eur Respir J 1998;12:540–545.
Monteiro RC, Hostoffer RW, Cooper MD, Bonner JR, Gartland GL, Kubagawa H: Definition of immunoglobulin A receptors on eosinophils and their enhanced expression in allergic individuals. J Clin Invest 1993;92:1681–1685.
Bracke M, Graaf E van de, Lammers JW, Coffer PJ, Koenderman L: In vivo priming of FcαR functioning on eosinophils of allergic asthmatics. J Leukoc Biol 2000;68:655–661.
Bracke M, Dubois GR, Bolt K, Bruijnzeel PL, Vaerman JP, Lammers JW, Koenderman L: 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. J Immunol 1997;159:1459–1465.
Bracke M, Lammers JW, Coffer PJ, Koenderman L: Cytokine-induced inside-out activation of FcαR (CD89) is mediated by a single serine residue (S263) in the intracellular domain of the receptor. Blood 2001;97:3478–3483.
Maliszewski CR, March CJ, Schoenborn MA, Gimpel S, Shen L: Expression cloning of a human Fc receptor for IgA. J Exp Med 1990;172:1665–1672.
de Wit TPM, Morton HC, Capel PJA, van de Winkel JGJ: Structure of the gene for the human myeloid IgA Fc receptor (CD89). J Immunol 1995;155:1203–1209.
van Vuuren AJ, van Egmond M, Coenen MJ, Morton HC, van de Winkel JG: Characterization of the human myeloid IgA Fc receptor I (CD89) gene in cosmid clone. Immunogenetics 1999;49:586–589.
Kremer EJ, Kalatzis V, Baker E, Callen DF, Sutherland GR, Maliszewski CR: The gene for the human IgA Fc receptor maps to 19q13.4. Hum Genet 1992;89:107–108.
Hoffjan S, Ober C: Present status on the genetic studies of asthma. Curr Opin Immunol 2002;14:709–717.
Shimokawa T, Tsuge T, Okumura K, Ra C: Identification and characterization of the promoter for the gene encoding the human myeloid IgA Fc receptor (FcαR, CD89). Immunogenetics 2000;51:945–954.
Morton HC, Schiel AE, Janssen SWJ, van de Winkel JGJ: Alternatively spliced forms of the human myeloid Fcα receptor (CD89) in neutrophils. Immunogenetics 1996;43:246–247.
Jasek M, Mańczak M, Sawaryn A, Obojski A, Wiśniewski A, Łuszczek W, Kuśnierczyk P: A novel polymorphism in the cytoplasmic region of the human immunoglobulin A Fc receptor gene. Eur J Immunogenet 2004;31:59–62.
Global Strategy for Asthma Management and Prevention. NHLBI/WHO Workshop Report, NIH Publication No 02-3659, February 2002.
Dreborg S, Backman A, Basomba A, Bousquet J, Digies P, Malling HI: Skin tests used in type I allergy testing. Position paper prepared by the Subcommittee on Skin Tests of the EAACI. Allergy 1989;44(Suppl 10):1–59.
Biometra TGGE System Manual. Göttingen, Biometra, 1999, pp 4–7.
Michaelides K, Schwaab R, Lalloz MRA, Schmidt W, Tuddenham EGD: Mutational analysis: New mutations; in McPherson MJ, Hames BD, Taylor GR (eds): PCR 2:A Practical Approach (Practical Approach Series). Oxford, Oxford University Press, 1995, pp 255–288.
Gille C, Gille A, Booms P, Robinson PN, Nurnberg P: Bipolar clamping improves the sensitivity of mutation detection by temperature gradient gel electrophoresis. Electrophoresis 1998;19:1347–1350.
Tsuge T, Shimokawa T, Horikoshi S, Tomino Y, Ra C: Polymorphism in promoter region of Fcα receptor gene in patients with IgA nephropathy. Hum Genet 2001;108:128–133.
Narita I, Goto S, Saito N, Sakatsume M, Jin S, Omori K, Gejyo F: Genetic polymorphisms in the promoter and 5′ UTR region of the Fcα receptor (CD89) are not associated with a risk of IgA nephropathy. J Hum Genet 2001;46:694–698.
Monteiro RC, van de Winkel JGJ: IgA Fc receptors. Annu Rev Immunol 2003;21:177–204.
Kita H, Masayuki K, Bartemes KR, Weiler DA, Schimming AW, Reed ChE, Gleich GJ: Does IgE bind to and activate eosinophils from patients with allergy? J Immunol 1999;162:6901–6911.
Abu-Ghazaleh RI, Fujisawa T, Mestecky J, Kyle RA, Gleich GJ: IgA-induced eosinophil degranulation. J Immunol 1989;142:2393–2400.
Pawlik A, Carlsson L, Meisel P, Czaja-Bulsa G, Mokrzycka M, Gawrońska-Szklarz B: The FcγRIIa polymorphism in children with atopic diseases. Int Arch Allergy Immunol 2004;133:233–238.
Wines BD, Sardjono CT, Trist HM, Lay C-S, Hogarth PM: The interaction of FcαRI with its implications for ligand binding by immunoreceptors of the leukocyte receptor cluster. J Immunol 2001;166:1781–1789.
Ding Y, Xu G, Yang M, Yao M, Gao GF, Wang L, Zhang W, Rao Z: Crystal structure of the ectodomain of human FcαRI. J Biol Chem 2003;278:27966–27970.
Herr AB, Ballister ER, Bjorkman PJ: Insights into IgA-mediated immune responses from the crystal structures of human FcαRI and its complex with IgA1-Fc. Nature 2003;423:614–620.
Shimokawa T, Ra C: C/EBPα and Ets protein family members regulate the human myeloid IgA Fc receptor (FcαRI, CD89) promoter. J Immunol 2003;170:2564–2572.
Lamkhioued B, Gounni AS, Gruart V, Pierce A, Capron A, Capron M: Human eosinophils express a receptor for secretory component. Role in secretory IgA-dependent activation. Eur J Immunol 1995;25:117–125.
Motegi Y, Kita H: Interaction with secretory component stimulates effector functions of human eosinophils but not of neutrophils. J Immunol 1998;161:4340–4346.
van Spriel AB, Leusen JHW, Vile H, van de Winkel JGJ: Mac-1 (CD11b/CD18) as accessory molecule for FcαR (CD89) binding of IgA. J Immunol 2002;169:3831–3836.
Grossetete B, Launay P, Lehuen A, Jungers P, Bach JF, Monteiro RC: Down-regulation of Fcα receptors on blood cells of IgA nephropathy patients: Evidence for a negative regulatory role of serum IgA. Kidney Int 1998;53:1321–1335.
Montenegro V, Chiamolera M, Launay P, Goncalves CR, Monteiro RC: Impaired expression of IgA Fc receptors (CD89) by blood phagocytic cells in ankylosing spondylitis. J Rheumatol 2000;27:411–417.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.