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DOI: 10.18544/PEDM-21.04.0040

Autoimmune gastritis among T1D individuals – important association?

Ewa Rusak, Agata Chobot

Key words

diabetes type 1, autoimmune gastritis, pernicious anemia, autoimmunity


The incidence of type 1 diabetes (T1D) is increasing. T1D and other autoimmune diseases have a similar, cell-specified pathogenesis. Due to an increased risk of autoimmune reactions, T1D subjects are statistically more often affected by other autoimmune diseases. During the course of the disease, patients with diabetes may develop, among others, anemia. When the classic and most common causes are excluded, a possibility of a concomitant autoimmune disorder has to be considered. In such cases, the differential diagnosis should  include autoimmune atrophic gastritis (AAG). The symptoms of AAG are: iron deficiency microcytic anemia and, thereafter, macrocytic anemia resultant from B12 vitamin deficiency, although nonspecific neurologic disorders may precede the diagnosis. Because autoimmune gastritis (AG) and its severe stage – pernicious anemia (PA) develop unperceptively over many years, often without any symptoms and frequently remain undiagnosed, physicians should closely screen T1D patients. Anti-parietal cell antibodies (APCA), targeting the gastric proton pump – the H+/K+ ATP-ase, are an advantageous tool for AAG screening, and are significantly more frequent among T1D subjects in comparison to the healthy population. That indicates an increased risk of AG. Some authors suggest that patients with T1D need to undergo a regular screening which includes: APCA, complete blood count, vitamin B12, iron and gastrin serum concentrations. Nevertheless, presently none of the official international or national guidelines for T1D treatment mention regular screening for AG.


The prevalence of autoimmune diseases is increasing. At present, approximately 9% of the general population is estimated to be affected by them [1, 2]. They tend to occur significantly more often in females [2,3]

The incidence of type 1 diabetes (T1D) in Europe is likewise increasing [4, 5]. T1D is a chronic autoimmune disorder, the base of which is a cell-mediated autoimmune reaction responsible for the loss of insulin-producing beta cells of pancreatic islets [6].

During the course of the disease patients with diabetes may develop, among others, anemia. The causes of anemia in T1D are multifactorial and frequently not completely clear and obvious. When the classic and most common causes are excluded, a possibility of a concomitant autoimmune disorder has to be considered. The differential diagnosis should, in such cases, include autoimmune atrophic gastritis (AAG) – a chronic, inflammatory disease of the gastric mucosa [7]. The permanent inflammatory infiltration is a result of a complex interaction between sensitized T cells and anti-parietal cell antibodies (APCA) [8–10]. AAG may progress to its final, severe stage – pernicious anemia (PA). AAG as well as PA develop unperceptively over many years and often without any symptoms [11]. Therefore, both diseases often remain undiagnosed, although they occur in people all over the globe [11–13]. 

In general, the incidence of AAG is estimated at ~2%, although AAG as well as PA seem to be under-diagnosed [8]. The incidence of both these diseases increases with age [8, 14]. AAG is more common in individuals with other autoimmune diseases, such as T1D, or thyroid diseases (in such patients its prevalence is comparatively three- to fivefold higher) [14]. In order to prevent the development of chronic symptoms and irreversible complications, early diagnosis and treatment of these conditions are imperative [3, 15]. This is particularly important inT1D patients, who are exposed to complications associated with the underlying disease. Often only severe complications, as in PA or resultant neurological disorders first suggest the diagnosis [16, 17].  

APCA are a serum biomarker of autoimmune gastritis. They are present in most patients with AAG and 85–90% of individuals with PA [10, 18, 19]. This fact makes APCA an advantageous tool for screening. Nevertheless,  the presence of these antibodies only is not sufficient for the diagnosis. It is because they are not specific for AAG or PA. They can also be found in the circulation of individuals with other autoimmune diseases [3, 18, 19]. The diagnostic tests for PA that monitor autoantibodies targeting intrinsic factor (IF) (a product of the parietal cell) are less sensitive (present only in 60% of patients), but more specific (98.6%) [3, 18, 20].

APCA circulating in the blood can be detected by means of various laboratory methods: immunofluorescence, enzyme-linked immunosorbent assay (EISA), and radioimmunoprecipitation assay (RIA). ELISA is currently the most commonly used method, while in RIA the 4A subunit has been optimized as a molecular-specific antigen probe [3, 10, 15, 21, 22]

The aim of this article is to present the current knowledge on the risk of autoimmune gastritis in patients with type 1 diabetes, diagnostic guidelines and therapeutic methods.

Genetic background 

T1D affects individuals with genetic susceptibility. These patients are exposed to the development of other autoimmune diseases (like autoimmune thyroid disorders, Addison – Biermer disease, celiac disease, vitiligo) [4]. Likewise, PA seems to be genetically determined, although the inheritance model is poorly understood. The occurrence between family members and coexistence with other autoimmune diseases (T1D, autoimmune thyroid diseases, vitiligo, and others) support the most likely theory of a genetic background of the disease. PA correlates with the B8DR3 haplotype. The identification of other genes responsible for the susceptibility is currently under investigation [23].

A study recognized an association between the presence of different autoantibodies (to GAD, IA-2, zinc transporter 8, autoantibodies against thyroid peroxidase (TPO), transglutaminase, 21-hydroxylase, APCA) and the susceptibility loci in individuals with T1D. The SNPs were identified in susceptibility loci: IFIH1, PTPN22, SH2B3, BACH2, and CTLA and a significant association with more than one autoantibody was noted. Furthermore, 11 loci were significantly associated with a single autoantibody. These results prove shared genetic background for T1D and other autoimmune diseases [24]

Wenzlau et al. identified a correlation between autoantibodies against ATP4a subunit of gastric parietal cells and variants in HLA class II, PTPN22, and CTLA4 genes. Moreover, among APCA positive individuals an increased frequency of DRB1*0404, DPB1*0201, and PTPN22 R620W (rs2476601-T) and a decreased frequency of DRB1*0101, DPB1*0301, and CTLA4 CT60 (rs3087243-T) were determined [25].

T1D and apca presence

APCA are a biomarker of autoimmune gastritis (AG) targeting the gastric proton pump – the H+/K+ ATP-ase. As evaluated by a meta-analysis APCA are significantly more frequent among T1D subjects in comparison to the healthy population [26, 27]. That indicates an increased risk of AG. The prevalence of AG and its severe stage – PA – among T1D individuals is 5-10%, and 2.6-4% respectively (relative to respectively 2% and 0.15-1% in the general population) [4, 28].

APCA are more prevalent in the serum of GADA-positive patients with T1D [29, 30] and are more common in adults (13% – 20%) than in children (5%) [27, 31]. It is worth noting that a study using the RIA showed APCA presence in 30% of the T1D children examined [32]. This finding may be related to the higher sensitivity of this method used to measure APCAs. In this study antibodies against the 4A subunit of the gastric proton pump were observed three times more frequently in females, but no correlation with age, age at diabetes diagnosis, diabetes duration or glycated hemoglobin A1c (HbA1c) was determined [32]. Alternatively, data from another study employing the RIA revealed increasing frequency of APCA positivity with age of T1D onset [15]. Additionally, a recent study found APCA in 20.9% of T1D patients – their prevalence was increasing with age and they were more common among females (25.3%) than in males (16.5%) [25]. Moreover, it was demonstrated that APCA positivity precedes the PA development by many years in T1D patients who present with hypergastrinemia and lower pepsinogen concentrations. In the same study, the benefit of simultaneously pepsinogen I and APCA determination is emphasized. Associated abnormal outcomes (low pepsinogen I together with APCA positivity) were determined as a prognostic marker of the development of B12 deficiency [33]. Also ghrelin, which is mainly produced in the stomach corpus, was assessed as a AG marker among T1D subjects, but was found not to be associated with the presence of AG [34]

Although advanced mucosa lesions are rare in T1D children, there are reports of histologic early AG symptoms [31], and even anemia with pancytopenia from vitamin B12 deficiency that required intramuscular injections [35]. Therefore, it is desirable that APCA positive T1D children should be closely screened. Although part of the patients becomes APCA-negative during the follow-up, the majority of them will achieve higher APCA levels and are at risk of developing AG [30].   

Anti-parietal cell antibodies

The target for APCA is the gastric proton pump – the H+/K+ ATP-ase [36, 37]. It is composed of four subunits: 2 alpha (100 kDa) and 2 beta (60-90 kDa) multipass transmembrane proteins. The proton pump functions to produce hydrochloric acid by exchanging cytoplasmic hydrogen ions for extracellular potassium ions [38]. The exported hydrogen ions combine with chloride ions to produce hydrochloric acid (HCl) [39] whereas the imported potassium ions are immediately transported outside of the cell by means of the Kir 4.1 channel. 

It has been demonstrated that APCA target both, the alpha, and highly glycosylated, beta subunits of the proton pump, although the major antigen for these autoantibodies is the alpha subunit [15, 21, 40]. The circulating APCA in the serum belong to three immunoglobulin classes: IgG, IgA, IgM in contrast to APCA found in the gastric juice which are classes IgG and IgA [18].

Circulating serum APCA can be detected by means of indirect immunofluorescence on histological samples. These results are semi-quantitative and qualitative, as they vary according to the experience of the technician [18].

Since the gastric H+/K+ ATP-ase has been proven to be the antigen for APCA, the diagnostic measures aiming to detect these antibodies were improved by the development of ELISA [41,42]. This method afforded concordance among labs and is approximately 30% more sensitive than immunofluorescence [22, 10]. The ELISA is quantitative, which facilitates monitoring of antibody titer [18]. Presently most investigators in the field utilize the ELISA to measure APCAs.

Another method used in APCA diagnosis is RIA, developed by scientists at the Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, USA. The 4A subunit of the H+/K+ ATP-ase, the main antigen for APCA, has been optimized as a molecular-specific antigen probe for these assays [15, 21]. In comparison to the ELISA, the RIA is a more accurate and precise method for the assessment of autoantibodies [43–46]. It may, therefore, also be a useful tool for early autoimmune gastritis and AAG screening [9, 10, 32, 47]. However RIA requires special laboratory conditions and specialist laboratory devices. 

Clinical consequences of Apca presence

The autoimmune reaction, mediated mainly by CD4 T cells reactive to the gastric proton pump and evidenced by the presence of APCA, leads to the destruction of parietal cells in the stomach [9, 10]. APCA detection in the serum indicates an increased risk for the development of AAG [48]. The consequence of the immune attack of the sensitized T cells over many years is the eventual atrophy of the stomach mucosa, especially in the body and fundus. Among others, the IF-producing parietal cells are destroyed. Consequently, the production of the HCl and IF is disturbed. IF is a cofactor required for vitamin B12 absorption in the ileum. Vitamin B12 itself is crucial for erythropoiesis and myelin production. Late stage AAG and progressive atrophy of the mucosa is classified as PA, the most common cause of vitamin B12 deficiency [10]

Nonetheless, profound megaloblastic anemia is not the only symptom of the disease. Neurologic disorders (numbness, paresthesia, weakness and ataxia) may precede anemia by many years [16–18]. Microcytic anemia may present earlier than megaloblastic anemia because an adequate acidity of the gastric environment is necessary for proper iron absorption. The developing achlorhydria leads to iron deficiency and ultimately to sideropenic anemia [49]. Therefore, the differential diagnostics in patients with an unknown cause of iron deficiency should include screening for autoimmune gastritis via ELISA or RIA as AAG is diagnosed in 20–27% of the former cases [50]. Likewise, among children with iron deficiency anemia of an unclear reason, refractory to oral supplementation, an associated autoimmune disease should be considered. A recently published study reports five cases of AAG in children with refractory iron deficiency anemia [51]. All of the observed patients were APCA positive, negative for IF autoantibodies and all revealed corpus atrophic gastritis with lymphocytic infiltration. That knowledge should alert physicians to implement appropriate diagnostic measures [51] 

Patients with AAG/PA are at a significantly higher risk of developing intestinal-type gastric adenocarcinoma, pyloric gland adenoma, squamous cell carcinomas (SCC), gastric carcinoid type I as well as other gastric carcinoid tumors [47, 52–54]. The overall relative risk of gastric cancer in patients with PA is 6.8 (95% CI 2.6-18.1) [53].

However, it should be noted, that not all APCA positive individuals fulfill the diagnostic criteria for AAG or PA. Remarkably, APCA are present also in 2.5–9% of healthy people [55]. Their prevalence in the general population rises with age. Recently published studies report APCA frequency of 7.8% in individuals from the Canary Islands and 19.5% in 50-74 year-olds from Germany [8, 56].

It is also noteworthy that the anemia develops longitudinally over many years. The antibodies must be persistent and at a sufficient concentration to elicit – together with autoreactive gastric CD4+ T cells – a local reaction and promote atrophy of the gastric mucosa and parietal cells [52]. Until now, the dynamics of APCA concentration relative to time and disease pathology have not been clearly determined. However, in patients with severe AAG, the disappearance of the antigen source due to an advanced mucosa atrophy results in lowering of the APCA titer [18].

Autoimmune polyglandular syndrome (Aps)

T1D and other autoimmune diseases have a similar, cell-specified pathogenesis. The humoral and cell-mediated immune response are responsible for a chronic inflammatory injury to tissues, organ-specific humoral reaction, and destruction of cells. Due to an increased risk of autoimmune reactions, T1D subjects are statistically more often affected by other autoimmune diseases [57]. Disorders associated with T1D are: autoimmune thyroid disease, most prevalent coexistence (15–30%), AG (5–10%), PA (2.6–4%), vitiligo (2–10%), Addison’s disease (0.5%) celiac disease (4%) [4, 57–59]. APS is defined as an autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. Gouveia et al. established an APS diagnosis in 25.2% of T1D patients, higher prevalence of autoimmune thyroiditis was observed in females. In the same study the frequency of markers for AG was assessed at 17.2% [60].

Glandular abnormalities known as APS type III include the following: T1D, autoimmune thyroid disease and AG [59]. This combination also affects young patients [35]. Therefore, it is necessary to regularly screen T1D individuals, particularly those subjects with organ-specific antibodies, for early diagnosis and initiation of treatment when  required [61]

Regular assessment of T1D patients

Based on the results of studies, some authors suggest that patients with T1D need to undergo a yearly screening which includes: complete blood count, vitamin B12, iron, and gastrin serum concentrations. They alsopropose  that APCA levels should be measured at the moment of diabetes diagnosis and then once yearly during the first 3 years, and at 5-year intervals thereafter. It is also suggested that subjects with an elevated gastrin titer and positive for APCA should be considered for a gastroscopic (with biopsy) evaluation at least once [62]. An examination should be performed urgently in case of any suspicious symptoms. It ought to be noted that within T1D patients, individuals with GADA and/or TPO high levels are at even higher risk of anemia development [28, 58, 62]

Nevertheless, presently none of the official international or national guidelines for T1D treatment (for example International Society for Pediatric and Adolescent Diabetes, American Diabetes Association, Diabetes Poland) mention regular screening for AG (APCA or iron/vitamin B12 concentrations) [63,64,65].

Treatment recommendations

Treatment depends on the stage of disease. As mentioned before, in early stages microcytic anemia from iron deficiency can occur, thereafter macrocytic – from B12 deficiency- develops. Early supplementation of iron and vitamin B12 respectively could protect from full-blown disorders. Iron can be supplemented orally or intravenously. Vitamin B12 is administered in intramuscular injections [28]

Apca and Helicobacter pylori infection 

Long-term Helicobacter pylori infection is one of the factors that can cause progressing atrophy of gastric mucosa [11]. An interesting and perpetual question to pose is whether APCA presence is related to Helicobacter pylori infection. The long-lasting discussion concerning this problem is still open. Although the majority of people infected with this bacteria are APCA negative [8, 66], these antibodies are found in up to 20.7% of these patients [8]

Thus Helicobacter pylori is implicated as one of the candidates causing AAG. However a study in T1D patients showed that the HLA susceptibility differs between those infected with Helicobacter pylori and subjects positive for APCA (Helicobacter pylori infection correlated with HLA-DQA1*0501-B1* 0201, while  APCA positivity with HLA-DQA1*0501-B1*0301) [67].


T1D affects individuals with an increasing frequency. Due to a shared genetic background and similar cell-specified pathogenesis, T1D subjects are statistically more often affected by other autoimmune diseases. The concomitant disorders are: autoimmune thyroid diseases, celiac disease, vitiligo, Addison’s disease, autoimmune atrophic gastritis and its severe stage – PA. Coexistence of more than one autoimmune condition known as APS occurs in approximately 25% of T1D patients. Because AG/PA develop unperceptively over many years, often without any symptoms and frequently remain undiagnosed, physicians should closely screen T1D patients. 

APCA are a good biomarker used to identify people at risk for development of AG/PA. APCA are significantly more frequent among T1D subjects, especially those GADA positive, in comparison to the healthy population. Likewise, low pepsinogen I together with APCA positivity are a prognostic marker of B12 deficiency development. Most common symptoms of AG are iron deficiency microcytic anemia and, thereafter, macrocytic anemia resultant from B12 vitamin deficiency, although neurologic disorders (numbness, paresthesia, weakness and ataxia) may precede anemia by many years. The role of early diagnosis is emphasized, as appropriate treatment may prevent irreversible complications occurrence. 


1. Cooper GS, Bynum ML, Somers EC. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun. 2009;33:197-207.

2. Hayter SM, Cook MC. Updated assessment of the prevalence, spectrum and case definition of autoimmune disease. Autoimmun Rev. 2012;11:754-65. 

3. Chapel H, Haeney M, Siraj M, Snowden N. Essentials of Clinical Immunology. Lublin: Czelej Sp.z.o.o.; 2009. 

4. Kahaly GJ, Hansen MP. Type 1 diabetes associated autoimmunity. Autoimmun Rev. 2016;1568-9972(16):30044-1. doi: 10.1016/j.autrev.2016.02.017. 

5. Patterson CC, Dahlquist GG, Gyurus E et al. Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study. Lancet. 2009;373:2027-2033. 

6. Van den Driessche A, Eenkhoorn V, Van Gaal L, De Block C. Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review. Neth J Med. 2009;67:376-387. 

7. Angelousi A, Larger E. Anaemia, a common but often unrecognized risk in diabetic patients: a review. Diabetes Metab. 2015;41:18-27. 

8. Zhang Y, Weck MN, Schöttker B et al. Gastric parietal cell antibodies, Helicobacter pylori infection, and chronic atrophic gastritis: evidence from a large population-based study in Germany. Cancer Epidemiol Biomarkers Prev. 2013;22:821-826.  

9. Neumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis–pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013;10:529-541.

10. Toh BH. Diagnosis and classification of autoimmune gastritis. Autoimmun Rev. 2014;13:459-462.

11. Neumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis–pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013;10:529-541. 

12. Carmel R. Prevalence of undiagnosed pernicious anemia in the elderly. Arch Intern Med. 1996;156:1097-1100.

13. Weck MN, Brenner H. Prevalence of chronic atrophic gastritis in different parts of the world Cancer. Epidemiol Biomarkers Prev. 2006;15:1083-1094. 

14. De Block CE, De Leeuw IH, Van Gaal LF. Autoimmune gastritis in type 1 diabetes: a clinically oriented review. J Clin Endocrinol Metab. 2008; 93:363-371.

15. Wenzlau JM, Gardner TJ, Frisch LM et al. Development of a novel autoantibody assay for autoimmune gastritis in type 1 diabetic individuals. Diabetes Metab Res Rev. 2011;27:887-890.

16. Tutaj A, Tomczykiewicz K, Zaleska B, Janda R. Neurologic signs in Addison-Biermer disease (report of 3 cases). Neurol Neurochir Pol. 1997;31:35-41. 

17. Rzepecki P, Nowosielski J, Kotowicz J, Betiuk B. Neurologic symptoms as the first manifestation of Addison-Biermer disease.  Wiad Lek. 1994;47:632-634. 

18. Bizzaro N, Antico A. Diagnosis and classification of pernicious anemia. Autoimmun Rev. 2014;13:565-568.

19. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med. 1999;159:1289-1298. 

20. Sedláková L, Dubská L, Průcha M. Pernicious anaemia–diagnostic benefit of the detection of autoantibodies against intrinsic factor and gastric parietal cells antigen H+/K+ ATPase. Epidemiol Mikrobiol Imunol. 2010;59:126-132. 

21. Song YH, Ma JY, Mårdh S et al. Localization of a pernicious anaemia autoantibody epitope on the alpha-subunit of human H,K-adenosine triphosphatase. Scand J Gastroenterol. 1994; 29:122-127. 

22. Toh BH, Kyaw T, Taylor R et al. Parietal cell antibody identified by ELISA is superior to immunofluorescence, rises with age and is associated with intrinsic factor antibody. Autoimmunity. 2012; 45:527-532. 

23. Andres E, Serraj K. Optimal management of pernicious anemia. J Blood Med. 2012;3:97-103. 

24. Brorsson CA, Pociot F. Type 1 Diabetes Genetics Consortium. Shared Genetic Basis for Type 1 Diabetes, Islet Autoantibodies, and Autoantibodies Associated With Other Immune-Mediated Diseases in Families with Type 1 Diabetes. Diabetes Care. 2015;38 Suppl 2:8-13. 

25. Wenzlau JM, Fain PR, Gardner TJ et al. ATPase4A Autoreactivity and Its Association with Autoimmune Phenotypes in the Type 1 Diabetes Genetics Consortium Study. Diabetes Care. 2015;38 Suppl 2:29-36. 

26. Pan XF, Gu JQ, Shan ZY. Type 1 Diabetic Populations Have an Increased Prevalence of Parietal Cell Antibody: A Systematic Review and Meta-Analysis. Medicine (Baltimore). 2015;94:e1440. 

27. Pinto AL, Dantas JR, Araujo D et al. Anti-parietal cell antibodies and pernicious anemia in patients with type 1 diabetes mellitus and multiethnic background. Diabetes Res Clin Pract. 2013;102:41-43. 

28. De Block CE, De Leeuw IH, Van Gaal LF. Autoimmune gastritis in type 1 diabetes: a clinically oriented review. J Clin Endocrinol Metab. 2008;93:363-371. 

29. De Block CEM, De Leeuw IH, Rooman RPA et al. Gastric parietal cell antibodies are associated with glutamic acid decarboxylase-65 antibodies and the HLA DQA1*0501-DQB1*0301 haplotype in type 1 diabetes. Diabet Med. 2000;17:618-622.

30. Kakleas K, Kostaki M, Critselis E et al. Gastric autoimmunity in children and adolescents with type 1 diabetes: a prospective study. Horm Res Paediatr. 2012;77:121-126.

31. Fröhlich-Reiterer EE, Huber J, Katz H et al. Do children and adolescents with type 1 diabetes mellitus have a higher frequency of parietal cell antibodies than healthy controls? J Pediatr Gastroenterol Nutr. 2011;52:558-562. 

32. Chobot A, Wenzlau J, Bak-Drabik K et al.  ATP4A autoimmunity and Helicobacter pylori infection in children with type 1 diabetes. Clin Exp Immunol. 2014;177:598-602. 

33. Alonso N, Granada ML, Soldevila B et al. Serum autoimmune gastritis markers, pepsinogen I and parietal cell antibodies, in patients with type 1 diabetes mellitus: a 5-year prospective study. J Endocrinol Invest.  2011;34:340-344. 

34. Alonso N, Granada ML, Salinas I et al. Plasma ghrelin concentrations in type 1 diabetic patients with autoimmune atrophic gastritis. Eur J Endocrinol. 2007;157:763-769.

35. Carneiro M, Dumont C. Pernicious anemia in an adolescent with type 1 diabetes mellitus. Arch Pediatr. 2009 Apr;16:357-359. 

36. Claeys D, Faller G, Appelmelk BJ et al. The gastric H+,K+-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy. Gastroenterology. 1998;115:340-347. 

37. Callaghan JM, Khan MA, Alderuccio F et al. Alpha and beta subunits of the gastric H+/K(+)-ATPase are concordantly targeted by parietal cell autoantibodies associated with autoimmune gastritis. Autoimmunity. 1993;16:289-295. 

38. Shin JM, Munson K, Sachs G. Gastric H+,K+-ATPase. Compr Physiol. 2011;1:2141-2153.

39. Sawicki W. Malejczyk J. Histology. Warszawa: Wydawnictwo Lekarskie PZWL;2012 [Digestive system]

40. Callaghan JM, Khan MA, Alderuccio F et al. Alpha and beta subunits of the gastric H+/K+-ATPase are concordantly targeted by parietal cell autoantibodies associated with autoimmune gastritis. Toh Autoimmunity. 1993;16:289-295.

41. Sugiu K, Kamada T, Ito M et al. Evaluation of an ELISA for detection of anti-parietal cell antibody. Hepatogastroenterology. 2006;53:11-14. 

42. Chuang JS, Callaghan JM, Gleeson PA, Toh BH. Diagnostic ELISA for parietal cell autoantibody using tomato lectin-purified gastric H+/K(+)-ATPase (proton pump). Autoimmunity. 1992;12:1-7. 

43. Kikkas I, Mallone R, Tubiana-Rufi N et al. A simple and fast non-radioactive bridging immunoassay for insulin autoantibodies. PLoS One. 2013;8:e69021. 

44. Wild T, Scherbaum WA, Gleichmann H et al. Comparison of a new anti-glutamic acid decarboxylase (GAD) enzyme-linked immunosorbent assay (ELISA) with radioimmunoassay methods: a multicenter study. Horm Metab Res. 1997;29:403-406.

45. Tandhanand-Banchuin N, Vannasaeng S, Ploybutr S, Sriussadaporn S. Comparison of anti-human insulin antibodies detection by commercial enzyme-linked immunosorbent assay kit, displacement enzyme-linked immunosorbent assay and radioimmunoassay, in Thai diabetic patients. Diabetes Res Clin Pract. 1993;22:71-82.

46. Greenbaum CJ, Palmer JP, Kuglin B, Kolb H. Insulin autoantibodies measured by radioimmunoassay methodology are more related to insulin-dependent diabetes mellitus than those measured by enzyme-linked immunosorbent assay: results of the Fourth International Workshop on the Standardization of Insulin Autoantibody Measurement. J Clin Endocrinol Metab. 1992;74:1040-1044.

47. Coati I, Fassan M, Farinati F et al. Autoimmune gastritis: Pathologist’s viewpoint. World J Gastroenterol. 2015; 21: 12179-12189. 

48. Tozzoli R, Kodermaz G, Perosa AR et al. Autoantibodies to parietal cells as predictors of atrophic body gastritis: a five-year prospective study in patients with autoimmune thyroid diseases. Autoimmun Rev. 2010;10:80-83. 

49. Hershko C, Ronson A, Souroujon M et al. Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion.  Blood. 2006;107:1673-1679. 

50. Hershko C, Patz J, Ronson A. The anemia of achylia gastrica revisited.  Blood Cells Mol Dis. 2007;39:178-183.

51. Gonçalves C, Oliveira ME, M Palha A et al. Autoimmune gastritis presenting as iron deficiency anemia in childhood. World J Gastroenterol.  2014;20:15780-15786. 

52. Lahner E, Annibale B. Pernicious anemia: new insights from a gastroenterological point of view. World J Gastroenterol.  2009;15:5121-5128. 

53. Vannella L, Lahner E, Osborn J, Annibale B. Systematic review: gastric cancer incidence in pernicious anaemia. Aliment Pharmacol Ther. 2013;37:375-382. 

54. Nguyen TL, Khurana SS, Bellone CJ et al. Autoimmune gastritis mediated by CD4+ T cells promotes the development of gastric cancer. Cancer Res. 2013;73:2117-2126. 

55. Alexandraki KI, Nikolaou A, Thomas D et al. Are patients with autoimmune thyroid disease and autoimmune gastritis at risk of gastric neuroendocrine neoplasms type 1? Clin Endocrinol (Oxf). 2014;80:685-690. 

56. Cabrera de León A, Almeida González D, Almeida AA et al. Factors associated with parietal cell autoantibodies in the general population. Immunol Lett.  2012;147:63-66. 

57. Piontek E, Witkowski D. Type 1 diabetes in children and other autoimmunological diseases. Nowa Pediatria. 2003;1:48-50

58. Witek PR, Witek J, Pańkowska E. Type 1 diabetes-associated autoimmune diseases: screening, diagnostic principles and management. Med Wieku Rozwoj. 2012;16:23-34.

59. Lam-Tse WK1, Batstra MR, Koeleman BP et al. The association between autoimmune thyroiditis, autoimmune gastritis and type 1 diabetes. Pediatr Endocrinol Rev. 2003;1:22-37.

60. Gouveia S, Gomes L, Ribeiro C, Carrilho F. Screening for autoimmune polyglandular syndrome in a cohort of patients with type 1 diabetes mellitus. Arq Bras Endocrinol Metabol. 2013;57:733-738.

61. Tsirogianni A, Pipi E, Soufleros K. Specificity of islet cell autoantibodies and coexistence with other organ specific autoantibodies in type 1 diabetes mellitus. Autoimmun Rev. 2009;8:687-691. 

62. De Block CE, De Leeuw IH, Bogers JJ et al. Autoimmune gastropathy in type 1 diabetic patients with parietal cell antibodies: histological and clinical findings. Diabetes Care. 2003;26:82-88.

63. Kordonouri O, Klingensmith G, Knip M et al. ISPAD. Clinical Practice Consensus Guidelines 2014. Pediatric Diabetes 2014: 15: 270-278.

64. American Diabetes Association. Standards of Medical Care in Diabetes–2016. Diabetes Care.2016;39(suppl.1):1-112.

65. Clinical guidelines for the management of patients with diabetes 2016. Statement of Diabetes Poland. Clinical Diabetology. 2016, tom 5, supl. A

66. Maciorkowska E, Kaczmarski M, Kondej-Muszyńska K et al. Anti-parietal cell antibodies in Helicobacter pylori associated gastritis. Nowa Pediatria. 2003;1:4-8. 

67. De Block CE, De Leeuw IH, Bogers JJ et al. Helicobacter pylori, parietal cell antibodies and autoimmune gastropathy in type 1 diabetes mellitus. Aliment Pharmacol Ther. 2002;16:281-289.

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2017; 23, 2: 59-116
2017; 23, 1: 1-58
2016; 22, 4: 133-180
2016; 22, 3: 81-132
2016; 22, 2: 43-79
2016; 22, 1: 1-42
2015; 21, 4: 149-191
2015; 21, 3: 97-148
2015; 21, 2: 51-96
2015; 21, 1: 1-50
2014; 20, 4: 131-182
2014; 20, 3: 83-130
2014; 20, 2: 35-82