**5.4 Treatment**

16 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights

Autoimmune gastritis, firstly described by Thomas Addison in 1849, is characterized by autoantibodies directed against gastric parietal cells, atrophy of gastric corpus and fundus, hypochlorhydria/achlorhydria, hypergastrinemia, iron deficiency anemia and pernicious

In *adult* general population the frequency of autoimmune gastritis is about 1-2%, and is 3-5 fold increased in patients with type 1 diabetes (De Block et al, 2008). As regards *children*, *adolescents* and *young adults* with type 1 diabetes, the frequency of parietal cells antibodies is 15.8%, with a close association with older age and duration of disease (De Block et al, 2008,

Antibodies against parietal cells (PCA) and their secretory product Intrinsic Factor (AIF) are serological markers for autoimmune gastritis and are targeted towards H+, K+-ATPase of gastric parietal cells and denote autoimmune gastritis, characterized by atrophy of corpus and fundus. The chronic auto-aggression to the proton pump exerts in hypochlorhydria/achlorhydria and hypergastrinemia and iron-deficiency anemia as a consequence of impaired gastric secretion and iron absorption. Moreover PCA are responsible for the reduced intrinsic factor secretion with subsequent pernicious anemia due to vitamin 12 deficiency. PCA and AIF are detectable not only in serum, but also in gastric juice. PCA titer is positively related to severity of gastric atrophy and negatively related to concentration of parietal cells. Low serum levels of pepsinogen I, as a consequence of chief cell destruction, represent another early marker of autoimmune gastritis and pernicious anemia. Both pernicious anemia and autoimmune gastritis may predispose to gastric cancer. Gastric adenocarcinomas are reported on 1-10 % of adult patients with autoimmune gastritis through intestinal meta/dysplasia. (De Block et al., 2003) Helicobacter Pylori infection has been reported as a risk factor for autoimmune gastritis, by stimulating granulocytes to produce oxygen radicals, which are mutagenic and lead to corpus atrophy (D'Elios et al., 2004). Molecular mimicry and/or T-helper l-induced expression of HLA-class II and costimulatory molecules on gastric epithelial cells are considered as pathogenic mechanisms for Helicobacter Pylori induced autoimmunity (Lahner et al., 2011). The evidence of a link between pernicious anemia and particular HLA haplo/genotypes is not strong. As regards type 1 diabetes, a weak association between PCA positivity and the HLA-DQA1\*0501- B1\*0301 haplotype, linked to HLA-DR5, has been observed. In mouse models, four distinct genetic regions that confer susceptibility to autoimmune gastritis have been identified: two loci, located on distal chromosome 4, are called *Gasa1* and *Gasa2*; two other loci, located on chromosome 6, are called *Gasa3* and *Gasa4,* respectively. Interestingly, three out of these four susceptibility loci are non-major histocompatibility complex genes which co-localize with those of type 1 diabetes. This is the strongest concordance identified between any two

Parietal cell antibodies are measured using immunoblotting or enzyme linked immunoassay (ELISA), which are more sensitive than indirect immunofluorescence technique. Iron deficiency anemia is defined as microcytic hypochromic anemia with a transferrine saturation of less than 20% and low iron and ferritin levels. Pernicious anemia is defined as macrocytic anemia with subnormal vitamin B12 levels and positive levels of PCAs

Warncke et al, 2010). Female gender association is controversial.

autoimmune disease so far (De Block et al., 2008).

**5.3 Diagnosis** 

anemia.

**5.2 Pathogenesis** 

Therapy of autoimmune gastritis includes supplementation of iron or vitamin B12 or removal of pre-malignant gastric lesions. Patients with PCA antibodies and high gastrin levels should undergo endoscopy with biopsies.

Determining risk factors for and early diagnosis of autoimmune gastritis is mandatory to prevent and treat iron-deficiency anemia, pernicious anemia and pre-malignant gastric lesions. In all PCA positive patients gastroscopy with multiple biopsies should be performed and subsequent clinical and endoscopic close follow-up are mandatory.
