**2. Antibodies as predictors of the GI autoimmune diseases**

The presence of autoantibodies in patient's serum has been considered a common symbol of autoimmune diseases. Autoantibodies are produced by pathogenic B cells, to target individual's own tissues. Many have considered them a clinical marker of diseases that can diagnose and predict prognosis of the disease. However, one GI disease can have more than one autoantibody, and many other diseases share the same autoantibodies. Some autoantibodies are specific to specific diseases, and some are not [3, 4]. This section is intended to give an overview of the most common and important autoantibodies in GI autoimmune diseases.

### **2.1 Anti-parietal cell antibody (APCA)**

Anti-parietal cell (APCA) is an autoantibody that targets H+/K+ ATPase, a heterodimer made of alpha- and beta-subunits. This enzyme is a proton pump located on parietal cells, that is involved in the production and release of high amount of hydrochloric acid [5]. Studies have shown that the isotypes of APCA immunoglobulins ate A, M, and G isotypes [6]. Many studies have associated APCA with autoimmune GI diseases, such as atrophic gastritis and Helicobacter pylori-associated atrophic gastritis. For example, H+/K+ ATPase has been considered a major antigen in H. pylori-associated antigastric autoimmunity [7]. Antibodies against this antigen are believed to have a crucial role in H. pylori-associated atrophic gastritis too. This was concluded by Ito et al., as the levels of APCA were significantly higher in patients with severe atrophy than in patients with mild atrophy (P = 0.01) [8]. Furthermore, H+/K+ ATPase is also a major antigen in autoimmune gastritis [9]. It is important to note that chronic gastritis, most commonly autoimmune gastritis and H. pylori gastritis, can result in atrophic gastritis [10]. To help identify atrophy, Claeys et al. state that APCA, which are closely associated with classical autoimmune gastritis, can be used as useful indicators for the atrophy of body mucosa in chronic H. pylori gastritis [7, 11].

Moreover, APCA can also predict one's risk for developing atrophic gastritis and its severity. For instance, Zhang et al. detected an overall APCA prevalence of 19.5%. They discovered that APCA prevalence was strongly associated with an approximately fourfold increased risk of chronic atrophic gastritis (CAG) (46.2% vs. 18.0%, adjusted OR = 3.8; 95% CI: 3.1–4.7). This striking association was even more increased with raising severity of chronic autoimmune gastritis (CAG) defined by PGI levels. As a result, they concluded that examining APCA levels might be a useful marker to be added when screening patients for CAG [11]. De Block et al. also conclude that

individuals with positive anti-gastric parietal cell are at a higher risk for atrophic gastritis [12]. To summarize, occurrence of APCA can help predict the development of atrophic gastritis in the future.
