Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1998 Jan 1;101(1):243–251. doi: 10.1172/JCI511

Anti-FcepsilonRIalpha autoantibodies in autoimmune-mediated disorders. Identification of a structure-function relationship.

E Fiebiger 1, F Hammerschmid 1, G Stingl 1, D Maurer 1
PMCID: PMC508561  PMID: 9421487

Abstract

Anti-FcepsilonRIalpha autoantibodies (autoAbs) occur and may be of pathogenetic relevance in a subset of chronic urticaria (CU) patients. To analyze the prevalence and magnitude of the humoral anti-FcepsilonRIalpha response in cohorts of CU patients compared with individuals suffering from classic skin- related (auto)immune diseases, we developed an ELISA system for the measurement of anti-FcepsilonRIalpha autoAbs in nonfractionated serum samples. Results obtained using this assay correlated well with those generated by Western blotting. We found IgG anti-FcepsilonRIalpha autoreactivity in 38% of CU patients but not in atopic dermatitis patients, psoriatics, or healthy individuals. We frequently detected anti-FcepsilonRIalpha autoAbs in pemphigus vulgaris (PV, 39%), dermatomyositis (DM, 36%), systemic lupus erythematosus (SLE, 20%), and bullous pemphigoid (BP, 13%). While the autoAb titers in DM, SLE, BP, and PV were similar to those encountered in CU patients, only anti-FcepsilonRIalpha+ CU serum specimens displayed pronounced histamine-releasing activity. The anti-FcepsilonRIalpha autoAbs in CU patients belong predominantly to the complement-fixing subtypes IgG1 and IgG3, whereas in DM, PV, and BP, they were found to be mainly of the IgG2 or IgG4 subtype. Complement-activating properties of anti-FcepsilonRIalpha autoAbs can indeed be of pathogenetic relevance, because C5a receptor blockade on basophils as well as decomplementation reduced drastically the histamine-releasing capacity of most anti-FcepsilonRIalpha-reactive CU sera. As a consequence, therapeutic efforts in CU should aim at altering not only the quantity but also the complement-activating properties of IgG anti-FcepsilonRIalpha autoAbs.

Full Text

The Full Text of this article is available as a PDF (242.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armant M., Ishihara H., Rubio M., Delespesse G., Sarfati M. Regulation of cytokine production by soluble CD23: costimulation of interferon gamma secretion and triggering of tumor necrosis factor alpha release. J Exp Med. 1994 Sep 1;180(3):1005–1011. doi: 10.1084/jem.180.3.1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Astier A., de la Salle H., Moncuit J., Freund M., Cazenave J. P., Fridman W. H., Hanau D., Teillaud J. L. Detection and quantification of secreted soluble Fc gamma RIIA in human sera by an enzyme-linked immunosorbent assay. J Immunol Methods. 1993 Nov 5;166(1):1–10. doi: 10.1016/0022-1759(93)90323-y. [DOI] [PubMed] [Google Scholar]
  3. Bischoff S. C., Schwengberg S., Wordelmann K., Weimann A., Raab R., Manns M. P. Effect of c-kit ligand, stem cell factor, on mediator release by human intestinal mast cells isolated from patients with inflammatory bowel disease and controls. Gut. 1996 Jan;38(1):104–114. doi: 10.1136/gut.38.1.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boros P., Odin J. A., Chen J., Unkeless J. C. Specificity and class distribution of Fc gamma R-specific autoantibodies in patients with autoimmune disease. J Immunol. 1994 Jan 1;152(1):302–306. [PubMed] [Google Scholar]
  5. Bürgi B., Brunner T., Dahinden C. A. The degradation product of the C5a anaphylatoxin C5adesarg retains basophil-activating properties. Eur J Immunol. 1994 Jul;24(7):1583–1589. doi: 10.1002/eji.1830240720. [DOI] [PubMed] [Google Scholar]
  6. Coffman R. L., Lebman D. A., Rothman P. Mechanism and regulation of immunoglobulin isotype switching. Adv Immunol. 1993;54:229–270. doi: 10.1016/s0065-2776(08)60536-2. [DOI] [PubMed] [Google Scholar]
  7. Fiebiger E., Maurer D., Holub H., Reininger B., Hartmann G., Woisetschläger M., Kinet J. P., Stingl G. Serum IgG autoantibodies directed against the alpha chain of Fc epsilon RI: a selective marker and pathogenetic factor for a distinct subset of chronic urticaria patients? J Clin Invest. 1995 Dec;96(6):2606–2612. doi: 10.1172/JCI118325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fiebiger E., Stingl G., Maurer D. Anti-IgE and anti-Fc epsilon RI autoantibodies in clinical allergy. Curr Opin Immunol. 1996 Dec;8(6):784–789. doi: 10.1016/s0952-7915(96)80005-7. [DOI] [PubMed] [Google Scholar]
  9. Füreder W., Agis H., Willheim M., Bankl H. C., Maier U., Kishi K., Müller M. R., Czerwenka K., Radaszkiewicz T., Butterfield J. H. Differential expression of complement receptors on human basophils and mast cells. Evidence for mast cell heterogeneity and CD88/C5aR expression on skin mast cells. J Immunol. 1995 Sep 15;155(6):3152–3160. [PubMed] [Google Scholar]
  10. Gavin A. L., Snider J., Hulett M. D., Mckenzie I. F., Hogarth P. M. Expression of recombinant soluble Fc epsilon RI: function and tissue distribution studies. Immunology. 1995 Nov;86(3):392–398. [PMC free article] [PubMed] [Google Scholar]
  11. Gerard C., Gerard N. P. C5A anaphylatoxin and its seven transmembrane-segment receptor. Annu Rev Immunol. 1994;12:775–808. doi: 10.1146/annurev.iy.12.040194.004015. [DOI] [PubMed] [Google Scholar]
  12. Giannini E., Boulay F. Phosphorylation, dephosphorylation, and recycling of the C5a receptor in differentiated HL60 cells. J Immunol. 1995 Apr 15;154(8):4055–4064. [PubMed] [Google Scholar]
  13. Grattan C. E., Francis D. M., Hide M., Greaves M. W. Detection of circulating histamine releasing autoantibodies with functional properties of anti-IgE in chronic urticaria. Clin Exp Allergy. 1991 Nov;21(6):695–704. doi: 10.1111/j.1365-2222.1991.tb03198.x. [DOI] [PubMed] [Google Scholar]
  14. Grattan C. E., Francis D. M., Slater N. G., Barlow R. J., Greaves M. W. Plasmapheresis for severe, unremitting, chronic urticaria. Lancet. 1992 May 2;339(8801):1078–1080. doi: 10.1016/0140-6736(92)90666-q. [DOI] [PubMed] [Google Scholar]
  15. Hide M., Francis D. M., Grattan C. E., Hakimi J., Kochan J. P., Greaves M. W. Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med. 1993 Jun 3;328(22):1599–1604. doi: 10.1056/NEJM199306033282204. [DOI] [PubMed] [Google Scholar]
  16. Huizinga T. W., van der Schoot C. E., Jost C., Klaassen R., Kleijer M., von dem Borne A. E., Roos D., Tetteroo P. A. The PI-linked receptor FcRIII is released on stimulation of neutrophils. Nature. 1988 Jun 16;333(6174):667–669. doi: 10.1038/333667a0. [DOI] [PubMed] [Google Scholar]
  17. Huston D. P., Bressler R. B. Urticaria and angioedema. Med Clin North Am. 1992 Jul;76(4):805–840. doi: 10.1016/s0025-7125(16)30327-3. [DOI] [PubMed] [Google Scholar]
  18. Inganäs M., Johansson S. G., Bennich H. Anti-IgE antibodies in human serum: occurrence and specificity. Int Arch Allergy Appl Immunol. 1981;65(1):51–61. doi: 10.1159/000232737. [DOI] [PubMed] [Google Scholar]
  19. Kalimo K., Jansen C. T. Treatment of chronic urticaria with an inhibitor of complement activation (cinnarizine). Ann Allergy. 1980 Jan;44(1):34–37. [PubMed] [Google Scholar]
  20. Kaplan A. P. Chronic urticaria. Possible causes, suggested treatment alternatives. Postgrad Med. 1983 Sep;74(3):209-15, 218-22. doi: 10.1080/00325481.1983.11698427. [DOI] [PubMed] [Google Scholar]
  21. Kirnbauer R. Papillomavirus-like particles for serology and vaccine development. Intervirology. 1996;39(1-2):54–61. doi: 10.1159/000150475. [DOI] [PubMed] [Google Scholar]
  22. Liszewski M. K., Farries T. C., Lublin D. M., Rooney I. A., Atkinson J. P. Control of the complement system. Adv Immunol. 1996;61:201–283. doi: 10.1016/s0065-2776(08)60868-8. [DOI] [PubMed] [Google Scholar]
  23. Metzger H. The high affinity receptor for IgE on mast cells. Clin Exp Allergy. 1991 May;21(3):269–279. doi: 10.1111/j.1365-2222.1991.tb01658.x. [DOI] [PubMed] [Google Scholar]
  24. Miletic V. D., Frank M. M. Complement-immunoglobulin interactions. Curr Opin Immunol. 1995 Feb;7(1):41–47. doi: 10.1016/0952-7915(95)80027-1. [DOI] [PubMed] [Google Scholar]
  25. Naito K., Hirama M., Okumura K., Ra C. Soluble form of the human high-affinity receptor for IgE inhibits recurrent allergic reaction in a novel mouse model of type I allergy. Eur J Immunol. 1995 Jun;25(6):1631–1637. doi: 10.1002/eji.1830250624. [DOI] [PubMed] [Google Scholar]
  26. Niimi N., Francis D. M., Kermani F., O'Donnell B. F., Hide M., Kobza-Black A., Winkelmann R. K., Greaves M. W., Barr R. M. Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria. J Invest Dermatol. 1996 May;106(5):1001–1006. doi: 10.1111/1523-1747.ep12338544. [DOI] [PubMed] [Google Scholar]
  27. Ravetch J. V., Kinet J. P. Fc receptors. Annu Rev Immunol. 1991;9:457–492. doi: 10.1146/annurev.iy.09.040191.002325. [DOI] [PubMed] [Google Scholar]
  28. Saban R., Haak-Frendscho M., Zine M., Ridgway J., Gorman C., Presta L. G., Bjorling D., Saban M., Jardieu P. Human FcERI-IgG and humanized anti-IgE monoclonal antibody MaE11 block passive sensitization of human and rhesus monkey lung. J Allergy Clin Immunol. 1994 Nov;94(5):836–843. doi: 10.1016/0091-6749(94)90151-1. [DOI] [PubMed] [Google Scholar]
  29. Sautès C., Varin N., Teillaud C., Daëron M., Even J., Hogarth P. M., Fridman W. H. Soluble Fc gamma receptors II (Fc gamma RII) are generated by cleavage of membrane Fc gamma RII. Eur J Immunol. 1991 Jan;21(1):231–234. doi: 10.1002/eji.1830210135. [DOI] [PubMed] [Google Scholar]
  30. Stadler B. M., Stämpfli M. R., Miescher S., Furukawa K., Vogel M. Biological activities of anti-IgE antibodies. Int Arch Allergy Immunol. 1993;102(2):121–126. doi: 10.1159/000236561. [DOI] [PubMed] [Google Scholar]
  31. Tong L. J., Balakrishnan G., Kochan J. P., Kinét J. P., Kaplan A. P. Assessment of autoimmunity in patients with chronic urticaria. J Allergy Clin Immunol. 1997 Apr;99(4):461–465. doi: 10.1016/s0091-6749(97)70071-x. [DOI] [PubMed] [Google Scholar]
  32. Wang B., Rieger A., Kilgus O., Ochiai K., Maurer D., Födinger D., Kinet J. P., Stingl G. Epidermal Langerhans cells from normal human skin bind monomeric IgE via Fc epsilon RI. J Exp Med. 1992 May 1;175(5):1353–1365. doi: 10.1084/jem.175.5.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Werfel T., Oppermann M., Begemann G., Götze O., Zwirner J. C5a receptors are detectable on mast cells in normal human skin and in psoriatic plaques but not in weal and flare reactions or in uticaria pigmentosa by immunohistochemistry. Arch Dermatol Res. 1997 Jan;289(2):83–86. doi: 10.1007/s004030050159. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES