McIntyre John A, Faulk W Page
HLA-Vascular Biology Laboratory, St. Francis Hospital and Health Care Centers, Beech Grove, IN 46107, USA.
Clin Rev Allergy Immunol. 2009 Aug;37(1):49-54. doi: 10.1007/s12016-008-8093-y.
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.
氧化还原反应能够“揭示”正常健康个体血液及其他体液中的自身抗体活性。这些“被揭示”的自身抗体即便与自身免疫性疾病相关的自身抗体不完全相同，也极为相似。引发这种揭示现象的物质是生理氧化剂，如血红素以及体内其他可能含有可参与氧化还原反应的过渡金属的天然分子。氧化型和非氧化型免疫球蛋白G（IgG）之间的实验室比较未能显示出差异，无法解释氧化诱导的抗体特异性改变。由氧化还原反应性揭示的自身抗体种类日益增多，其中许多负责调节细胞内功能。相比之下，同种抗体，如抗人白细胞抗原（HLA）抗体，对氧化诱导的自身抗体改变不敏感，这表明形成这些各自抗体分子互补决定区的氨基酸存在差异。我们提出，抗体反应性的这种可逆氧化转化代表了一种迄今未被发现但进化保守的固有体液免疫资源，旨在维持免疫稳态。
