Abstract
In autoantibody-mediated autoimmune diseases, pathogenic autoantibodies generated by a failure of central or peripheral tolerance, have different effects mediated by a variety of mechanisms. Interestingly, even non-autoimmune chronic diseases have a set of disease-specific natural autoantibodies that are maintained for a long time. Because most of these natural autoantibodies target intracellular proteins or long non-coding RNAs, they are speculated to be non-pathological and have some important as yet unrecognized physiological functions such as debris clearance. Recently, we revealed a set of disease-specific natural autoantibodies of chronic pulmonary diseases with unknown etiology by protein arrays that enable detection of specific autoantibodies against >8000 targets. Surprisingly, some of the targeted antigens of disease-specific autoantibodies were subsequently reported by other laboratories as strongly associated with the disease, suggesting that these antigens reflect the pathology of each disease. Furthermore, some of these autoantibodies that target extracellular antigens might modify the original course of each disease. Here, we review the disease-specific natural autoantibodies of chronic pulmonary diseases, including chronic fibrosing idiopathic interstitial pneumonias, sarcoidosis, and autoimmune pulmonary alveolar proteinosis, and discuss their utility and effects.
Highlights
An antibody, called an immunoglobulin, is a protective protein produced by the immune system in response to the presence of foreign substances, including antigens
We showed that 17.5% of a cohort of chronic fibrosing interstitial pneumonias (IIPs) had high titers of serum anti-myxovirus resistance-protein 1 (MX1) autoAbs above the cut-off value, i.e., mean + 4 SD of healthy individuals, by ELISA [12]
Pulmonary alveolar proteinosis (PAP) encompasses chronic lung disorders characterized by the accumulation of surfactant-derived material in pulmonary alveoli, which is accompanied by varying degrees of respiratory insufficiency [67]
Summary
Called an immunoglobulin, is a protective protein produced by the immune system in response to the presence of foreign substances, including antigens. Recent studies have shown that sera of patients with or without autoimmune diseases contain IgG autoAbs that react with a set of self-antigens and are unique to each disease [7,8]. These so-called natural autoAbs usually react with intracellular proteins and long non-coding RNAs, and are thought to have evolved as an adaptive mechanism for functions such as debris clearance, which is consistent with their utility as diagnostic and prognostic indicators of disease [8]. Natural autoAbs are sometimes generated against the cell surface or secreted proteins, which might modify the course of the original disease. This review summarizes the recent insights into natural autoAbs in chronic pulmonary diseases and their potential relevance to the disease course
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