Nature Medicine
8, 694 - 701 (2002)
Published online: 17 June 2002; | doi:10.1038/nm722
Immunoglobulin-free light chains elicit immediate hypersensitivity-like responsesFrank A. Redegeld1, Maurice W. van der Heijden1, Mirjam Kool1, Bianca M. Heijdra1, Johan Garssen2, Aletta D. Kraneveld1, Henk Van Loveren2, Paul Roholl2, Takashi Saito3, J. Sjef Verbeek4, Jill Claassens4, Andries S. Koster1
& Frans P. Nijkamp11
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
2
National Institute of Public Health and the Environment, Bilthoven, the Netherlands
3
Department of Molecular Genetics, Chiba University, Chuo-ku, Chiba, Japan
4
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
Correspondence should be addressed to Frank A. Redegeld f.a.m.redegeld@pharm.uu.nlImmunoglobulin (Ig)-free light chains IgLC are present in serum and their production is augmented under pathological conditions such as multiple sclerosis, rheumatoid arthritis and neurological disorders. Until now, no (patho)physiological function has been ascribed to circulating Ig light chains. Here we show that IgLCs can confer mast cell−dependent hypersensitivity in mice. Antigenic stimulation results in plasma extravasation, cutaneous swelling and mast-cell degranulation. We show that IgLCs have a crucial role in development of contact sensitivity, which could be completely prevented by a novel IgLC antagonist. Although IgE and IgG1 are central to the induction of immediate hypersensitivity reactions, our results show that IgLCs have similar activity. IgLCs may therefore be a novel factor in the humoral immune response to antigen exposure. Our findings open new avenues in investigating the pathogenesis of autoimmune diseases and their treatments.
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