Autoimmune gastritis (AIG) is a chronic inflammatory condition affecting the stomach lining. The immune system mistakenly attacks its own healthy stomach cells, specifically targeting the acid-producing cells. This leads to their damage and eventual loss, distinguishing AIG from other forms of gastritis caused by infections or irritants.
Understanding Autoimmunity
The immune system, which normally defends against foreign invaders, becomes misdirected in autoimmune gastritis. It targets components of the stomach’s parietal cells. These specialized cells, located in the stomach lining, produce hydrochloric acid for digestion and intrinsic factor, a protein crucial for vitamin B12 absorption.
The immune system’s attack involves specific autoantibodies. Anti-parietal cell antibodies (APCA) target the H+/K+-ATPase proton pump on parietal cells. This pump is important for acid secretion, and its destruction reduces stomach acid production, a condition known as hypochlorhydria or achlorhydria. Anti-intrinsic factor antibodies (IFA) directly interfere with intrinsic factor’s function.
The presence of both APCA and IFA indicates an ongoing autoimmune process. The destruction of parietal cells and the binding of IFAs to intrinsic factor hinder vitamin B12 absorption. Over time, this can lead to a vitamin B12 deficiency, necessary for red blood cell production and neurological function. While APCA are sensitive markers for AIG, IFA are more specific, appearing later in disease progression.
Genetic Predisposition
An individual’s genetic makeup plays a significant role in susceptibility to autoimmune gastritis. AIG often runs in families, suggesting an inherited component. Certain genetic markers, particularly within the human leukocyte antigen (HLA) system, are linked to an increased risk.
HLA genes are part of the major histocompatibility complex (MHC), which helps the immune system distinguish between the body’s own cells and foreign substances. Specific alleles, such as HLA-DRB104 and DQB103, are more common in individuals with AIG. These genetic variations can influence immune function, potentially predisposing an individual to an autoimmune response against stomach cells.
Beyond HLA genes, other genetic variations have been identified as risk factors. These include genes like PTPN22, PNPT1, and IL2RA, which are involved in immune regulation. Genes responsible for gastric acid secretion, such as ATP4A and ATP4B, have also been implicated. While genetic factors increase the likelihood of developing AIG, they do not guarantee its onset, indicating other influences are also at play.
Environmental Factors
External elements can act as triggers or contributors to autoimmune gastritis, especially in genetically predisposed individuals. Infections are notable environmental factors, with Helicobacter pylori (H. pylori) bacteria often discussed. The relationship between H. pylori and AIG is complex; some research suggests it may contribute to AIG through mechanisms like molecular mimicry, where bacterial antigens resemble self-antigens, leading to an immune attack on the stomach’s own cells.
Paradoxically, in some cases, H. pylori infection might protect against AIG, or its eradication could potentially unmask the autoimmune process. The interplay between H. pylori strains, host genetics, and the resulting immune response is not fully understood.
Other potential environmental influences include prolonged use of certain medications, such as non-steroidal anti-inflammatory drugs (NSAIDs), excessive alcohol consumption, and physical trauma. While dietary factors are often explored in autoimmune conditions, direct causal links to AIG are less established. These environmental interactions are thought to initiate the autoimmune response in susceptible individuals.
Co-occurring Autoimmune Disorders
Autoimmune gastritis frequently presents alongside other autoimmune conditions, highlighting a broader systemic predisposition to autoimmunity. Individuals diagnosed with one autoimmune disease have an increased likelihood of developing additional ones. This clustering of conditions suggests shared underlying genetic or environmental factors that contribute to a generalized autoimmune susceptibility.
Common co-occurring disorders include autoimmune thyroid diseases like Hashimoto’s thyroiditis, Type 1 diabetes, and Addison’s disease. Other associated conditions are vitiligo, Sjogren’s syndrome, rheumatoid arthritis, and autoimmune hepatitis. The presence of these conditions does not directly cause AIG, but rather indicates a heightened immune system reactivity that can target multiple organs.
For example, a significant percentage of patients with autoimmune thyroid disease also have AIG, and vice versa. This interconnectedness underscores the importance of considering AIG in individuals with other autoimmune diagnoses, even if stomach symptoms are not prominent. Recognizing these associations helps in understanding the complex nature of autoimmune conditions.