Abstract
Oxidation–reduction (redox) reactions can “unmask” autoantibody activity in blood and other body fluids from normal, healthy individuals. These “unmasked” autoantibodies are similar if not identical to autoantibodies associated with autoimmune diseases. The agents responsible for this unmasking are physiological oxidants such as hemin and likely other naturally occurring molecules in the body that contain transitional metals available for participation in redox reactions. Laboratory comparisons between oxidized and non oxidized IgG fail to show differences to account for the oxidation-induced alteration of antibody specifics. The autoantibodies unmasked by redox reactivities represent a growing list of specificities, many that are responsible for modulating and/or regulating intracellular functions. In contrast, alloantibodies, such as anti-HLA antibodies, do not exhibit susceptibility to oxidation-induced autoantibody alterations, suggesting differences in the amino acids responsible for forming the complementarity determining regions of these respective antibody molecules. We have proposed that such reversible oxidative conversions of antibody reactivities represent a heretofore undiscovered, but an evolutionary-conserved, resource of innate humoral immunity destined to maintain an immunological homeostasis.
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References
Shoenfeld Y, Gershwin ME, Meroni PL (eds) (2008) Autoantibodies, 2nd edn. Elsevier, Philadelphia
Silverstein AM (2001) Autoimmunity versus horror autotoxicus: the struggle for recognition. Nat Immunol 2:279–281
National Institutes of Health, The Autoimmune Diseases Coordinating Committee (2005) Progress in autoimmune diseases research. Report to Congress. U.S. Department of Health and Human Services, March
Gershwin LJ (2007) Veterinary autoimmunity: autoimmune diseases in domestic animals. Ann N Y Acad Sci 1109:109–116
McIntyre JA (2004) The appearance and disappearance of antiphospholipid antibodies subsequent to oxidation–reduction reactions. Thromb Res 114:579–587
McIntyre JA, Wagenknecht DR, Faulk WP (2005) Autoantibodies unmasked by redox reactions. J Autoimmun 24:311–317
McIntyre JA, Wagenknecht DR, Faulk WP (2003) Antiphospholipid antibodies: discovery, definition, detection and disease. Prog Lipid Res 42:176–237
McIntyre JA, Wagenknecht DR, Faulk WP (2006) Redox-reactive autoantibodies: detection and physiological relevance. Autoimmun Rev 5:76–83
Fellouse FA, Barthelemy PA, Kelley RF, Sidhu SS (2006) Tyrosine plays a dominant functional role in the paratope of a synthetic antibody derived from a four amino acid code. J Mol Biol 357:100–114
Cabiedes J, Cabral AR, Alarcón-Segovia (1998) Hidden anti-phospholipid antibodies in normal human sera circulate as immune complexes whose antigen can be removed by heat, acid, hypermolar buffers or phospholipase treatments. Eur J Immunol 7:2108–2114
Lorber M, Shoenfeld Y (2000) Hidden autoantibodies. Clin Rev Allergy Immunol 1:51–58
Tomer Y, Shoenfeld Y (1988) The significance of natural autoantibodies. Immunol Invest 5:389–424
Matsuura E, Hughes GRV, Khamashta MA (2008) Oxidation of LDL and its clinical implication. Autoimmun Rev 7:558–566
Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320:915–924
Tabuchi M, Inoue K, Usui-Kataoka H, Kobayashi K, Teramoto M, Takasugi K et al (2007) The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis. J Lipid Res 48:768–781
Shoenfeld Y, Wu R, Dearing LD, Matsuura E (2004) Are anti-oxidized low-density lipoprotein antibodies pathogenic or protective? Circulation 110:2552–2558
Matsuura E, Kobayashi K, Tabuchi M, Lopez LR (2006) Oxidative modification of low-density lipoprotein and immune regulation of atherosclerosis. Prog Lipid Res 45:466–486
Camejo G, Halberg C, Monschik-Lundin A et al (1998) Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages. J Lipid Res 39:755–766
Miller YI, Shaklai N (1999) Kinetics of hemin distribution in plasma reveals its role in lipoprotein oxidation. Biochim Biophys Acta 1454:153–164
McIntyre JA, Faulk WP (eds) (2008) Special issue: redox and autoimmunity. Autoimmun Rev 7:515–584
Acknowledgements
We thank Dr. Chinpal Kim, Purdue University, for Fig. 6 and Dr. Christiane Hampe, University of Washington, for Fig. 7. Mr. Napoleon Monce, Immunoconcepts, Sacramento, CA contributed to Table 1.
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McIntyre, J.A., Faulk, W.P. Redox-Reactive Autoantibodies: Biochemistry, Characterization, and Specificities. Clinic Rev Allerg Immunol 37, 49–54 (2009). https://doi.org/10.1007/s12016-008-8093-y
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DOI: https://doi.org/10.1007/s12016-008-8093-y