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Development of a novel autoantibody assay for autoimmune gastritis in type 1 diabetic individuals
Author(s) -
Wenzlau J. M.,
Gardner T. J.,
Frisch L. M.,
Davidson H. W.,
Hutton J. C.
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1267
Subject(s) - autoimmune gastritis , autoantibody , pernicious anaemia , type 1 diabetes , medicine , atrophic gastritis , immunology , biomarker , autoimmune disease , population , antigen , autoimmunity , disease , gastritis , antibody , gastroenterology , diabetes mellitus , helicobacter pylori , endocrinology , biology , biochemistry , environmental health
Abstract Background Autoimmune atrophic body gastritis (ABG) and pernicious anaemia are prototypical, organ‐specific autoimmune diseases whose prevalence in the general population is 2.0 vs 2 and 0.15–1%, respectively. The incidence of disease increases with age and is frequently associated with other autoimmune disorders such as type 1 diabetes mellitus (T1DM). Early diagnosis of ABG/pernicious anaemia is essential for the prevention and/or treatment before manifestations of chronic disease become irreversible. Parietal cell autoantibody detection via enzyme‐linked immunosorbent assay is currently the most widely used biomarker of disease with diagnosis confirmed by subsequent immunohistochemistry via biopsy. Methods To improve the assay we designed a specific, molecularly defined radioimmunoprecipitation assay for early detection of ABG, targeting its major antigen, the gastric H + /K + ATPase 4A subunit ATP4A. Results The major antigenic domain in ATP4A was tested against a panel of sera from new onset patients with T1DM which tested positive for the gold standard T1DM autoantibodies (IAA, IA2A, GAD65A, and ZnT8A). Significant immunoreactivity to ATP4A was measured (25%) while 6% of first‐degree relatives of subjects with T1DM who were sero‐negative for T1DM autoantigens were positive for ATP4A autoantibodies. ATP4A antibody prevalence increased with age of onset of T1DM, which is atypical of other T1DM autoantibodies. Immunoreactivity to ATP4A, unlike that of T1DM antigens, demonstrates a significant gender bias in newly diagnosed individuals with T1DM. Conclusion Although the utility of the assay as a biomarker for T1DM is likely limited, it may serve as an improved indicator of ABG. Copyright © 2011 John Wiley & Sons, Ltd.