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Published in: Journal of Clinical Immunology 1/2010

Open Access 01-05-2010

Anti-amyloidogenic Activity of IgGs Contained in Normal Plasma

Authors: Brian O’Nuallain, Angela D. Williams, Helen P. McWilliams-Koeppen, Luis Acero, Alfred Weber, Hartmut Ehrlich, Hans P. Schwarz, Alan Solomon

Published in: Journal of Clinical Immunology | Special Issue 1/2010

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Abstract

Introduction

We have previously shown that a subpopulation of naturally occurring human IgGs has therapeutic potential for the amyloid-associated disorders. These molecules cross-react with conformational epitopes on amyloidogenic assemblies, including amyloid beta (Aβ) protein fibrils that are a pathological hallmark of Alzheimer’s disease.

Materials and Methods

Using our europium-linked immunosorbant assay, we established that ∼95% of 260 screened donor plasma samples had amyloid fibril-reactive IgGs and Aβ conformer-reactive IgGs with minimal binding to Aβ monomers. Anti-amyloidogenic reactivity was diverse and attributed to Aβ targeting multiple fibril-related binding sites and/or variations in multidentate binding.

Results and Discussion

There was no correlation between anti-fibril and anti-oligomer reactivity and donor age (19 to 60 years old) or gender. These findings demonstrate the inherent but diverse anti-amyloidogenic activity of natural IgGs contained in normal plasma.

Conclusion

Our studies provide support for investigating the clinical significance and physiological function of this novel class of antibodies.
Literature
1.
go back to reference Stefani M. Protein misfolding and aggregation: new examples in medicine and biology of the dark side of the protein world. Biochim Biophys Acta. 2004;1739:5–25.PubMed Stefani M. Protein misfolding and aggregation: new examples in medicine and biology of the dark side of the protein world. Biochim Biophys Acta. 2004;1739:5–25.PubMed
2.
go back to reference Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, et al. Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature. 1992;359:322–5.CrossRefPubMed Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, et al. Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature. 1992;359:322–5.CrossRefPubMed
3.
4.
go back to reference Moir RD, Tseitlin KA, Soscia S, Hyman BT, Irizarry MC, Tanzi RE. Autoantibodies to redox-modified oligomeric Abeta are attenuated in the plasma of Alzheimer's disease patients. J Biol Chem. 2005;280:17458–63.CrossRefPubMed Moir RD, Tseitlin KA, Soscia S, Hyman BT, Irizarry MC, Tanzi RE. Autoantibodies to redox-modified oligomeric Abeta are attenuated in the plasma of Alzheimer's disease patients. J Biol Chem. 2005;280:17458–63.CrossRefPubMed
5.
go back to reference Falk RH, Skinner M. The systemic amyloidoses: an overview. Adv Intern Med. 2000;45:107–37.PubMed Falk RH, Skinner M. The systemic amyloidoses: an overview. Adv Intern Med. 2000;45:107–37.PubMed
6.
go back to reference Solomon A, Weiss DT, Wall JS. Immunotherapy in systemic primary (AL) amyloidosis using amyloid-reactive monoclonal antibodies. Cancer Biother Radiopharm. 2003;18:853–60.CrossRefPubMed Solomon A, Weiss DT, Wall JS. Immunotherapy in systemic primary (AL) amyloidosis using amyloid-reactive monoclonal antibodies. Cancer Biother Radiopharm. 2003;18:853–60.CrossRefPubMed
7.
go back to reference Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005;64:1553–62.CrossRefPubMed Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005;64:1553–62.CrossRefPubMed
8.
go back to reference Klyubin I, Betts V, Welzel AT, Blennow K, Zetterberg H, Wallin A, et al. Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization. J Neurosci. 2008;28:4231–7.CrossRefPubMed Klyubin I, Betts V, Welzel AT, Blennow K, Zetterberg H, Wallin A, et al. Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization. J Neurosci. 2008;28:4231–7.CrossRefPubMed
10.
go back to reference Dodel RC, Du Y, Depboylu C, Hampel H, Frölich L, Haag A, et al. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2004;75:1472–4.CrossRefPubMed Dodel RC, Du Y, Depboylu C, Hampel H, Frölich L, Haag A, et al. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2004;75:1472–4.CrossRefPubMed
11.
go back to reference Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, et al. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging. 2009;30:1728–36.CrossRefPubMed Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, et al. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging. 2009;30:1728–36.CrossRefPubMed
12.
go back to reference .O'Nuallain B, Acero L, Williams AD, Koeppen HP, Weber A, Schwarz HP, et al. Human plasma contains cross-reactive Abeta conformer-specific IgG antibodies. Biochemistry. 2008;47:12254–6.CrossRefPubMed .O'Nuallain B, Acero L, Williams AD, Koeppen HP, Weber A, Schwarz HP, et al. Human plasma contains cross-reactive Abeta conformer-specific IgG antibodies. Biochemistry. 2008;47:12254–6.CrossRefPubMed
13.
go back to reference O'Nuallain B, Hrncic R, Wall JS, Weiss DT, Solomon A. Diagnostic and therapeutic potential of amyloid-reactive IgG antibodies contained in human sera. J Immunol. 2006;176:7071–8.PubMed O'Nuallain B, Hrncic R, Wall JS, Weiss DT, Solomon A. Diagnostic and therapeutic potential of amyloid-reactive IgG antibodies contained in human sera. J Immunol. 2006;176:7071–8.PubMed
14.
go back to reference Li Q, Gordon M, Cao C, Ugen KE, Morgan D. Improvement of a low pH antigen-antibody dissociation procedure for ELISA measurement of circulating anti-Abeta antibodies. BMC Neurosci. 2007;8:22.CrossRefPubMed Li Q, Gordon M, Cao C, Ugen KE, Morgan D. Improvement of a low pH antigen-antibody dissociation procedure for ELISA measurement of circulating anti-Abeta antibodies. BMC Neurosci. 2007;8:22.CrossRefPubMed
15.
go back to reference Kuo YM, Emmerling MR, Lampert HC, Hempelman SR, Kokjohn TA, Woods AS, et al. High levels of circulating Abeta42 are sequestered by plasma proteins in Alzheimer's disease. Biochem Biophys Res Commun. 1999;257:787–91.CrossRefPubMed Kuo YM, Emmerling MR, Lampert HC, Hempelman SR, Kokjohn TA, Woods AS, et al. High levels of circulating Abeta42 are sequestered by plasma proteins in Alzheimer's disease. Biochem Biophys Res Commun. 1999;257:787–91.CrossRefPubMed
16.
go back to reference Baril L, Nicolas L, Croisile B, Crozier P, Hessler C, Sassolas A, et al. Immune response to Abeta-peptides in peripheral blood from patients with Alzheimer's disease and control subjects. Neurosci Lett. 2004;355:226–30.CrossRefPubMed Baril L, Nicolas L, Croisile B, Crozier P, Hessler C, Sassolas A, et al. Immune response to Abeta-peptides in peripheral blood from patients with Alzheimer's disease and control subjects. Neurosci Lett. 2004;355:226–30.CrossRefPubMed
17.
go back to reference Mruthinti S, Buccafusco JJ, Hill WD, Waller JL, Jackson TW, Zamrini EY, et al. Autoimmunity in Alzheimer's disease: increased levels of circulating IgGs binding Abeta and RAGE peptides. Neurobiol Aging. 2004;25:1023–32.CrossRefPubMed Mruthinti S, Buccafusco JJ, Hill WD, Waller JL, Jackson TW, Zamrini EY, et al. Autoimmunity in Alzheimer's disease: increased levels of circulating IgGs binding Abeta and RAGE peptides. Neurobiol Aging. 2004;25:1023–32.CrossRefPubMed
18.
go back to reference Xu W, Kawarabayashi T, Matsubara E, Deguchi K, Murakami T, Harigaya Y, et al. Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls. Brain Res. 2008;1219:169–79.CrossRefPubMed Xu W, Kawarabayashi T, Matsubara E, Deguchi K, Murakami T, Harigaya Y, et al. Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls. Brain Res. 2008;1219:169–79.CrossRefPubMed
19.
go back to reference Istrin G, Bosis E, Solomon B. Intravenous immunoglobulin enhances the clearance of fibrillar amyloid-beta peptide. J Neurosci Res. 2006;84:434–43.CrossRefPubMed Istrin G, Bosis E, Solomon B. Intravenous immunoglobulin enhances the clearance of fibrillar amyloid-beta peptide. J Neurosci Res. 2006;84:434–43.CrossRefPubMed
20.
go back to reference Du Y, Wei X, Dodel R, Sommer N, Hampel H, Gao F, et al. Human anti-beta-amyloid antibodies block beta-amyloid fibril formation and prevent beta-amyloid-induced neurotoxicity. Brain. 2003;126:1935–9.CrossRefPubMed Du Y, Wei X, Dodel R, Sommer N, Hampel H, Gao F, et al. Human anti-beta-amyloid antibodies block beta-amyloid fibril formation and prevent beta-amyloid-induced neurotoxicity. Brain. 2003;126:1935–9.CrossRefPubMed
Metadata
Title
Anti-amyloidogenic Activity of IgGs Contained in Normal Plasma
Authors
Brian O’Nuallain
Angela D. Williams
Helen P. McWilliams-Koeppen
Luis Acero
Alfred Weber
Hartmut Ehrlich
Hans P. Schwarz
Alan Solomon
Publication date
01-05-2010
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue Special Issue 1/2010
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-010-9413-6

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