Elsevier

Autoimmunity Reviews

Volume 10, Issue 2, December 2010, Pages 80-83
Autoimmunity Reviews

Review
Autoantibodies to parietal cells as predictors of atrophic body gastritis: A five-year prospective study in patients with autoimmune thyroid diseases

https://doi.org/10.1016/j.autrev.2010.08.006Get rights and content

Abstract

Autoimmune thyroid diseases (AITD) can be associated with autoimmune gastritis (AIG), but the frequency of this association is poorly characterized. We performed a prospective study to: a) characterize the frequency of parietal cell (PCA) and intrinsic factor (IFA) autoantibodies in AITD patients; b) evaluate the development of histologically- and functionally-proven AIG after five years and to assess the predictive role of PCA for AIG at baseline; and c) analyze the trend of PCA levels in the course of the disease. We studied 208 consecutive adult patients affected by AITD (166 Hashimoto's thyroiditis, 42 Graves’ disease). PCA, IFA and plasma gastrin levels were measured with ELISA methods at baseline and after 5 years. At baseline, 51/208 (24.5%) AITD patients were positive for PCA and 10/208 (4.8%) for IFA. 25 out of 54 PCA/IFA-positive AITD patients (all without gastric or haematologic symptoms) agreed to participate in the follow-up study. After 5 years, 6 (24%) of these 25 patients showed a histologically proven AIG, with lymphocytic infiltration and/or atrophy of body gastric mucosa. The trend analysis of PCA concentration showed that autoantibody levels rise progressively over time, reach a peak level and then fall, according to the progressive destruction of gastric mucosa and to the disappearance of the target autoantigen (proton pump). The presence of PCA predicts the development of autoimmune gastritis in AITD patients. Antibody levels measured with a sensitive quantitative immunometric method are useful for early diagnosis and early treatment of the disease.

Introduction

Autoimmune gastritis (AIG) is a common and frequently underdiagnosed disease, with a prevalence of nearly 2% in the general population [1], [2]. AIG is characterized by atrophy of the corpus and fundus of the stomach, and by the serum presence of autoantibodies to the parietal cells (PCA) directed against the proton pump (H+/K+ATPase), and of autoantibodies to the intrinsic factor (IFA). The autoimmune attack to the parietal cells may result in decreased acid secretion, hypergastrinemia, iron-deficient anemia [3], pernicious anemia due to vitamin B12 deficiency, and gastric malignant tumours (carcinoid and adenocarcinoma) related to intestinal metaplasia and entero-chromaffin-like hyperplasia or dysplasia [4]. For these reasons, early diagnosis of AIG is extremely important to prevent and treat iron-deficient anemia, pernicious anemia and premalignant gastric lesions.

In the general population, the prevalence of PCA increases with age, from 2.5% in the third decade to 12% in the eighth decade. The prevalence is even higher in patients affected by other autoimmune diseases, especially autoimmune thyroid diseases (AITD) and type 1 diabetes (T1DM) [5], [6]. These associations define the multiple autoimmune diseases (MAS) type 3B and 4 [7], [8].

The immunological association between AITD and AIG was first suggested in the early 1960s [9]. The term thyrogastric autoimmunity, initially coined for the association of AITD with pernicious anemia [10], was later extended for defining all associations between AITD and AIG.

Although AIG has been extensively studied in patients with AITD, its prevalence varies widely in literature reports, depending on the type of patient studied (children or adults, overt AIG or only PCA/IFA positivity) and the diagnostic accuracy of the immunological methods used for the detection of AIG-associated autoantibodies [11], [12], [13], [14].

In addition, another aspect not yet investigated is the trend of autoantibody levels during the progression of AIG.

Section snippets

A prospective study in AITD patients

In a five-year prospective study on AITD patients, we aimed to test and characterize: a) the frequency of PCA/IFA (to define incomplete MAS 3B) at enrollment; b) the development of histologically- and functionally-proven AIG (complete MAS 3B) after five years, in order to assess the predictive role of PCA for AIG at baseline; and c) the trend of PCA levels during the follow-up.

Two hundred and eight consecutive adult patients with AITD were studied, 166 of whom were affected by Hashimoto's

Results

Using the 95 percentile of value distribution in healthy subjects, the cut-off levels obtained for PCA and IFA were 20 U/mL and 12 U/mL, respectively. According to these threshold values, we found that, at baseline sampling, 51/208 patients (24.5%) were positive for PCA and 10/208 (4.8%) were positive for IFA (7 patients were positive for both antibodies).

The prevalence of PCA-positivity in GD patients (11/42, 26.2%) was only slightly higher than in HT patients (40/166, 24.1%). Conversely, the

Discussion

This study had three main objectives: a) to assess the prevalence of PCA and IFA in AITD patients; b) to assess the positive predictive value of PCA for autoimmune gastritis in AITD patients; and c) to characterize antibody levels during the clinical course of AIG.

In our series of 208 adult patients affected by AITD, we found a prevalence of 24.5% of PCA detected by ELISA, which is much higher than that reported in normal adults without AITD (2–12%) [1], [2], but is similar to the prevalence

Take-home messages

  • Parietal cell autoantibodies are present nearly in 25% of patients affected by autoimmune thyroid diseases.

  • During a five-year follow-up, 24% of asymptomatic AITD patients with detectable levels of PCA at baseline developed an overt autoimmune gastritis.

  • In the natural history of autoimmune gastritis, the concentrations of parietal cell antibodies rise progressively, rich a peak level and then fall, according to the progressive destruction of gastric mucosa.

  • The quantitative measurement of

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