Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses

F.A. Redegeld; M.W. van der Heijden; M. Kool; B.M. Heijdra; J. Garssen; A.D. Kraneveld; H. van Loveren; P. Rhoholl; T. Saito; S. Verbeek; J. Claassens; A.S. Koster; F.P. Nijkamp

doi:10.1038/nm722

Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses

F.A. Redegeld^*, M.W. van der Heijden, M. Kool, B.M. Heijdra, J. Garssen, A.D. Kraneveld, H. van Loveren, P. Rhoholl, T. Saito, S. Verbeek, J. Claassens, A.S. Koster, F.P. Nijkamp

^*Corresponding author for this work

NUTRIM School of Nutrition and Translational Research in Metabolism

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses.

Redegeld FA, van der Heijden MW, Kool M, Heijdra BM, Garssen J, Kraneveld AD, Van Loveren H, Roholl P, Saito T, Verbeek JS, Claassens J, Koster AS, Nijkamp FP.

Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands. f.a.m.redegeld@pharm.uu.nl

Immunoglobulin (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 IgG(1) 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.

Original language	English
Pages (from-to)	694-701
Number of pages	7
Journal	Nature Medicine
Volume	8
Issue number	7
DOIs	https://doi.org/10.1038/nm722
Publication status	Published - 1 Jan 2002

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10.1038/nm722

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@article{9e54652ee28047afb75fe83b037ab8c4,

title = "Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses",

abstract = "Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses.Redegeld FA, van der Heijden MW, Kool M, Heijdra BM, Garssen J, Kraneveld AD, Van Loveren H, Roholl P, Saito T, Verbeek JS, Claassens J, Koster AS, Nijkamp FP.Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands. 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 IgG(1) 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.",

author = "F.A. Redegeld and {van der Heijden}, M.W. and M. Kool and B.M. Heijdra and J. Garssen and A.D. Kraneveld and {van Loveren}, H. and P. Rhoholl and T. Saito and S. Verbeek and J. Claassens and A.S. Koster and F.P. Nijkamp",

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AU - Redegeld, F.A.

AU - van der Heijden, M.W.

AU - Kool, M.

AU - Heijdra, B.M.

AU - Garssen, J.

AU - Kraneveld, A.D.

AU - van Loveren, H.

AU - Rhoholl, P.

AU - Saito, T.

AU - Verbeek, S.

AU - Claassens, J.

AU - Koster, A.S.

AU - Nijkamp, F.P.

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N2 - Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses.Redegeld FA, van der Heijden MW, Kool M, Heijdra BM, Garssen J, Kraneveld AD, Van Loveren H, Roholl P, Saito T, Verbeek JS, Claassens J, Koster AS, Nijkamp FP.Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands. 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 IgG(1) 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.

AB - Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses.Redegeld FA, van der Heijden MW, Kool M, Heijdra BM, Garssen J, Kraneveld AD, Van Loveren H, Roholl P, Saito T, Verbeek JS, Claassens J, Koster AS, Nijkamp FP.Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands. 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 IgG(1) 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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