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Conditional autoimmunity mediated by human natural anti-FcRI autoantibodies?

MICHAEL P. HORN^*,1, JANA M. PACHLOPNIK^*, MONIQUE VOGEL^*, MARKUS DAHINDEN^*, FLORIAN WURM, BEDA M. STADLER^* and SYLVIA M. MIESCHER^*,2

^* Institute of Immunology and Allergology, Inselspital, CH-3010 Bern, Switzerland;
Laboratory of Cellular Biotechnology, Center for Biotechnology UNIL-EPFL, EPFL, CH-1015 Lausanne, Switzerland; and
ZLB Bioplasma AG, CH-3022 Bern, Switzerland

²Correspondence: Institute of Immunology and Allergology, Sahlihaus 1, Inselspital, CH-3010 Bern, Switzerland. E-mail: sylvia.miescher{at}insel.ch

Natural antibodies provide an early defense mechanism against pathogens, show a frequent self-reactivity, and are present throughout life. Two questions concern the physiological control of self-reactivity and the pathogenetic link to autoimmune disease. Here we propose a concept of conditional autoimmunity involving natural antibodies against the chain of the high-affinity receptor for IgE (FcRI). Like other natural antibodies, anti-FcRI antibodies are found in sera of healthy donors. We now report the first human recombinant anti-FcRI autoantibodies isolated by repertoire cloning from a human tonsillar IgM library. These high-affinity antibodies recognize FcRI on cells and trigger histamine release from freshly isolated blood basophils. However, the latter effect requires IgE removal from the FcRI. The same conditional histamine release is seen when using sera from individual normal donors and affinity-purified anti-FcRI antibodies isolated from multidonor therapeutic IgG preparations. We propose that such anti-FcRI antibodies can become pathogenic and that this is dependent on the state of occupancy of the FcRI by its natural ligand IgE. We suggest that an imbalance between FcRI occupancy and natural anti-FcRI antibodies may be implicated in the pathogenesis of autoimmune urticaria.—Horn, M. P., Pachlopnik, J. M., Vogel, M., Dahinden, M., Wurm, F., Stadler, B. M., Miescher, S. M. Conditional autoimmunity mediated by human natural anti-FcRI autoantibodies?

Key Words: natural autoantibodies • phage display • IgE receptor

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