Development of a novel autoantibody assay for autoimmune gastritis in type 1 diabetic individuals

Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA.
Diabetes/Metabolism Research and Reviews (Impact Factor: 3.55). 11/2011; 27(8):887-90. DOI: 10.1002/dmrr.1267
Source: PubMed


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.
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.
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.
Although the utility of the assay as a biomarker for T1DM is likely limited, it may serve as an improved indicator of ABG.

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    • "The overall higher incidence of organ-specific autoimmunity of approximately 50% detected in our study was mainly due to the inclusion of gastric ATPase autoantibodies which were not previously tested in parallel with other organ-specific autoantibodies. The prevalence of anti-gastric ATPase autoantibodies in approximately 16–24% of T1D subjects in the two different DASP cohorts is also consistent with other published findings that used immunofluorescence [13], [24] and recently developed radioimmunoprecipitation assay [36]. In contrast to previous studies [24], [37], no significant association of anti-gastric autoantibodies was detected with autoantibodies against GAD65 or TPO in our cohort, but this lack of correlation in our study may be due to our small sample size. "
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