Abstract
Autoimmune gastritis is characterised by lymphocytic infiltration of the gastric submucosa, with loss of parietal and chief cells and achlorhydria. Often, gastritis is expressed clinically as cobalamin deficiency with megaloblastic anaemia, which is generally described as a disease of the elderly. Here, we report on two prepubertal children who developed autoimmune gastritis. One child developed autoimmune gastritis as part of a polyglandular autoimmune disease from a family with polyglandular autoimmune disease type II (PGA type II) and the other as part of a classic “thyro-gastric cluster,” which may have been triggered by emotional trauma. Both children presented with normal small bowel biopsies, with abnormal gut permeability, which subsequently resolved. These patients are among the youngest reported to date. The immune systems targetted the gastric parietal cell autoantigens (ATP4A and ATP4B) in both children, similar to the elderly. The study of children with autoimmune gastritis and their families may provide additional insights into the disease’s pathogenesis and may also lead to the identification of inheritable factors influencing susceptibility. This report underlines the necessity to screen paediatric patients with organ-specific autoimmune diseases for co-existent conditions. Children with polyglandular autoimmune disease are at particularly high risk.
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References
Baxter AG, Jordan MA, Silveira PA, Wilson WE, van Driel IR (2005) Genetic control of susceptibility to autoimmune gastritis. Int Rev Immunol 24:55–62
Bjarnason I, MacPherson A, Hollander D (1995) Intestinal permeability: an overview. Gastroenterology 108:1566–1581
Burman P, Kampe O, Kraaz W, Loof L, Smolka A, Karlsson A, Karlsson-Parra A (1992) A study of autoimmune gastritis in the postpartum period and at a 5-year follow-up. Gastroenterology 103:934–942
Carmel R (1988) Pepsinogens and other serum markers in pernicious anaemia. Am J Clin Pathol 90:442–445
Carmel R (1996) Prevalence of undiagnosed pernicious anemia in the elderly. Arch Intern Med 156:1097–1100
Carmel R, Johnson CS (1978) Racial patterns in pernicious anemia. Early age at onset and increased frequency of intrinsic-factor antibody in black women. N Engl J Med 298:647–650
Cobden I, Rothwell J, Axon AT (1980) Intestinal permeability and screening tests for coeliac disease. Gut 21:512–518
D’Elios MM, Amedei A, Azzurri A, Benagiano M, Del Prete G, Bergman MP, Vandenbroucke-Grauls CM, Appelmelk BJ (2005) Molecular specificity and functional properties of autoreactive T-cell response in human gastric autoimmunity. Int Rev Immunol 24:111–122
Dickey W, Kenny BD, McMillan SA, Porter KG, McConnell JB (1997) Gastric as well as duodenal biopsies may be useful in the investigation of iron deficiency anaemia. Scand J Gastroenterol 32:469–472
Doniach D, Roitt IM, Taylor KB (1965) Autoimmunity in pernicious anemia and thyroiditis: a family study. Ann NY Acad Sci 124:605–625
Faller G, Kirchner T (2005) Immunological and morphogenic basis of gastric mucosa atrophy and metaplasia. Virchows Arch 446:1–9
Frenkel EP, Yardley DA (2000) Clinical and laboratory features and sequelae of deficiency of folic acid (folate) and vitamin B12 (cobalamin) in pregnancy and gynecology. Hematol Oncol Clin North Am 14:1079–100
Gordon MM, Brada N, Remacha A, Badell I, del Río E, Baiget M, Santer R, Quadros EV, Rothenberg SP, Alpers DH (2004) A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency. Hum Mutat 23:85–91
Greenwood DLV, Sentry JW, Toh BH (2001) Characterisation of proton pump antibodies and stomach pathology in gastritis induced by neonatal immunisation without adjuvant. Autoimmunity 34:81–94
Harrakahi MSE (1996) Pernicious anaemia in Arabs. Blood Cells Mol Dis 22:98–103
Hart A, Kamm MA (2002) Mechanisms of initiation and perpetuation of gut inflammation by stress. Aliment Pharmacol Ther 16:2017–2028
Houston GA, Files JC, Morrison FS (1985) Race, age, and pernicious anemia. South Med J 78:69–70
Irvine WJ, Cullen DR, Mawhinney H (1974) Natural history of autoimmune achlorhydric atrophic gastritis. A 1–15-year follow-up study. Lancet 2:482–485
Jiskra J, Límanová Z, Vanícková Z, Kocna P (2003) IgA and IgG antigliadin, IgA anti-tissue transglutaminase and antiendomysial antibodies in patients with autoimmune thyroid diseases and their relationship to thyroidal replacement therapy. Physiol Res 52:79–88
Katz S, Berernheim J, Kaufman Z, Lazar L, Erez I, Wolach B (1997) Pernicious anemia and adenocarcinoma of the stomach in an adolescent: clinical presentation and histopathology. J Pediatr Surg 32:1384–1385
Kaye MD, Whorwell PJ, Wright R (1983) Gastric mucosal lymphocyte subpopulations in pernicious anemia and in normal stomach. Clin Immunol Immunopathol 28:431–440
Kocak R, Paydas S (1992) Pernicious anemia in Turkey. Int J Hematol 55:117–119
Landolt MA, Vollrath M, Ribi K, Gnehm HE, Sennhauser FHJ (2003) Incidence and associations of parental and child posttraumatic stress symptoms in pediatric patients. J Child Psychol Psychiatry 44:1199–1207
Malagon I, Onkenhout W, Klok G, van der Poel PF, Bovill JG, Hazenkamp MG (2005) Gut permeability in paediatric cardiac surgery. Br J Anaesth 94:181–185
Marshall AC, Toh BH, Alderuccio F (2004) Tumor necrosis factor alpha is not implicated in the genesis of experimental autoimmune gastritis. J Autoimmun 22:1–11
Morale C, Brouwer J, Testa N, Tirolo C, Barden N, Dijkstra CD, Amor S, Marchetti B (2001) Stress, glucocorticoids and the susceptibility to develop autoimmune disorders of the central nervous system. Neurol Sci 22:159–162
Oliva-Hemker M, Berkenblit GV, Anhalt GJ, Yardley JH (2006) Pernicious anemia and widespread absence of gastrointestinal endocrine cells in a patient with autoimmune polyglandular syndrome type I and malabsorption. J Clin Endocrinol Metab 91:2833–2838
Pontiroli AE, Falsetti L, Bottazzo G (1987) Clinical, endocrine, roentgenographic, and immune characterization of hyperprolactinemic women. Int J Fertil 32:81–85
Riordan SM, McIver CJ, Thomas DH, Duncombe VM, Bolin TD, Thomas MC (1997) Luminal bacteria and small-intestinal permeability. Scand J Gastroenterol 32:556–563
Rooyakkers DR, van Eijk HM, Deutz NE (1996) Simple and sensitive multi-sugar-probe gut permeability test by high-performance liquid chromatography with fluorescence labelling. J Chromatogr A 730:99–105
Schaberg JW, Howden CW (1998) Gastric as well as duodenal biopsies may be useful in the investigation of iron deficiency anaemia (IDA). Gastrointest Endosc 48:107–108
Segni M, Borrelli O, Pucarelli I, Delle Fave G, Pasquino AM, Annibale B (2004) Early manifestations of gastric autoimmunity in patients with juvenile autoimmune thyroid diseases. J Clin Endocrinol Metab 89:4944–4948
Strickland R, Mackay IR (1973) A reappraisal of the nature and significance of chronic atrophic gastritis. Am J Dig Dis 18:426–440
te Velde K, Abels J, Anders GJPA, Arends PJ, Hoedemaker PJ, Nieweg HO (1964) A family study of pernicious anemia by an immunologic method. J Lab Clin Med 64:177–187
Toh BH, van Driel IR, Gleeson PA (1997) Pernicious anemia. N Engl J Med 337:1441–1448
Travis S, Menzies I (1992) Intestinal permeability: functional assessment and significance. Clin Sci (Lond) 82:471–488
Wangel AG, Callender ST, Spray GH, Wright R (1968) A famiy study of pernicious anaemia. I. Autoantibodies, achlorhydria, serum pepsinogen and vitamin B12. Br J Haematol 14:161–181
Whittingham S, Ungar B, Mackay IR, Mathews JD (1969) The genetic factor in pernicious anaemia. A family study in patients with gastritis. Lancet 1:951–954
Wolters M, Ströhle A, Hahn A (2004) Cobalamin: a critical vitamin in the elderly. Prev Med 39:1256–1266
Acknowledgements
Many thanks go to Antje Haase, Royal Darwin Hospital, for performing the analyses for the gut permeability testing and to Professor David Brewster and Associate Professor Edward O’Loughlin for their helpful suggestions. Many thanks also go to Dr. Wendy Webb for referring patient #1 and to Dr. Philip Rack for referring patient #2. D.L.V.G was a recipient of the NH&MRC (Dora Lush) Biomedical Research Scholarship at the time of this study.
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D.L.V.G. and P.C. contributed equally to this manuscript.
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Greenwood, D.L.V., Crock, P., Braye, S. et al. Autoimmune gastritis and parietal cell reactivity in two children with abnormal intestinal permeability. Eur J Pediatr 167, 917–925 (2008). https://doi.org/10.1007/s00431-007-0664-z
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DOI: https://doi.org/10.1007/s00431-007-0664-z