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Autoimmimity in pectic ulceration
Homed. & Pharmacother., Q Elsevier, Paris
43 (1989)
571-572
571
utoi R.M. KIRK Royal Free Hospital, London NW3 2OG, UK (Received
2 May
1989;
Gastric autoimmunity is well recognised in gastric atropy with associated pernicious anaemia-type A gastritis of Strickland and Mackay [16]. Autoantibodies to parietal cells also occur in some patients with Type R gastritis [I]. There is no proof that peptic ulcers have an autoimmune connection, but there is some circumstantial evidence to suggest this. If peptic ulcers in different sites are acknowledged to be related, then the damaged mucosa seen in gastritis associated particularly with gastric ulcer, and the parietal cell hyperplasia sometimes associated with duodenal ulcer evoke comp~son with autoimmune th~oiditis and autoimmune stimulation of the thyroid in “primary” thyrotoxicosis. Sirtori [14] in 1971 found plasma cells in biopsy specimens taken from duodenal ulcers at operation. Their endoplasmic reticulum was transformed into vesicles filled with proteinic material having a periodical structure of 200 A which he took be immunoglobulin A (IgA). He considered that the plasma cells might be an expression of a local autoimmune phenomenon brought about by ulcer-related antigens. In 1982 Rotter and Heiner (121 suggested that antibodies to secretory immunoglobulin may be over-represented in childhood duodenal ulcer subjects and allergic populations, leading to ulceration due to a deficiency in local mucosal immune defences. They also postulated that an immunoglobulin might be stimulatory to acid secretion. In 1979 Vandelli et al. [17] detected autoantibodies that reacted exclusively with gastrin producing (G) cells. De Lazzari et al. [2] also reported that immunoglobulin G (IgG), obtained from patients with duodenal ulcer stimulated gastric
accepted
24 June
1989)
acid secretion when injected into rats, by an action on the histamine receptors (H2-R}. It has been argued that gastric and duodenal ulcers form a continuum [5], with a small parietal cell area and low acid output in patients with proximal gastric ulcer, and an enlarged parietal cell area with normal or high acid output in patients with duodenal ulcer. In the ZollinerEllison syndrome the parietal cell area occupies virtually the whole stomach, the acid output is very high and the ulcers tend to be distally placed 191.Gastrin is not only stimulatory to acid output by parietal cells, but is trophic to them [4]. In gastric and duodenal ulcers the ulcer develops in mucosa damaged by gastritis or duodenitis [3, 4, 8, 13, 13. This is the area in which G cells are found and in gastritis with intestinal metaplasia, G cells are absent [lo, 151.Thus, peptic ulcers develop in a background of extension or retraction of the parietal cells and damage to the distal stomach and duodenal bulb-the area where G cells occur. Stimulation of the G cells would bring about extension of the parietal cell area as occurs in duodenal ulcer patients, and damage to them might produce the appearance of gastroduodenitis with sus~eptibili~ to acid attack and reduction of the trophic effect on the parietal cell area. This is very analogous to the immune mechanisms in the thyroid gland where destruction or stimulation of the parenchymal cells may occur, leading on the one hand to thyroiditis or on the other hand to thyrotoxicosis. Pathology of other paracrine glands may also be involved 1111. Thus, autoimmune mechanisms have been identified in some but by no means all peptic ulcer patients. The subject is worthy of further study 161.
572
R.&i. Kirk
Coghill N.E., Doniach D. & Roitt I.M. (1965) Autoantibodies in simple atrophic gastritis. Gut 6,48 De Lazzari F., Mirakian R., Venturi C., Bortalami M., Naccarato R., Doniach D. & Bottazzo G.F. (1985) Are there immunological forms of duodenal ulcer (DW) as a consequence of gastric parietal cell stimulating antobodies (PCS-Ab) ? Gut 26, Al 116 Gear M.W.L., Truelove S.C. ipt Whitehead R. (1971) Gastric ulcer and gastritis. Gut 12, 639 Johnson L.R. (1979) Regulation of gastrointestinal mucosal growth. WorldJ. Surg. 3, 477 Kirk R.M. (1981) Are gastric and duodenal ulcers separate diseases or do they form a continuum ? Big. Dis- Sci. 26, 149 Kirk RM. (1986) Could chronic peptic ulcers be localised areas of acid susceptibility generated by autoimmunity ? Lancet i, 772 Konjetzny GE. (1938) Der Mugenkrebs. Enke, Stuttgart Meikle D.D., Taylor K.B., Truelove SC. & Whitehead R. (1976) Gastritis, duodenitis, and eircuIating levels of gastrin in duodenal ulcers before and after vagotomy. Gur 17, 719 Neuberger P., Lewin M. & Bonlils S. (1972) Parietal and chief cell population in four cases of Zollinger-Ellison syndrome. Gastroenterulogy63, 937
10 Ottenjann R., Meiderer SE. Br Elster K. (1969) Forceps biopsy from the antrum, corpus and cardia of the stomach under endoscopic control. K&n. Wocherischr.47, 859 11 Polak J.M., Bloom S.R., Bishop A.E. 8c McCrossan M.V. (1978) D cell pathology in duodenal ulcers and achlorhydria. Metabolism 27 (suppl I), 1239 12 Rotter J.I. & Heiner DC. (1982) Are there immunologic forms of duodenal ulcer ? .I. C&n. Lab. Immrrnol. 7, 1 13 Schade R.O.K. (1966) Chronic gastritis. In : Recent Advances in Gastroenterology. Proc. World Congress of Gastroenterology, Tokyo, 2, 84 14 Sirtori L. (1971) Ulcer-related antigens ? Br. Med. J. 1, 403 15 Stadelmann O., Elster K. 8r Stoke M. (1971) The peptic gastric ulcer-histopathographic and functional investigations. &and. J. Gustroenterol.6, 613 16 Strickland R.G. dc Mackay I.R. (1973) A reappraisal of the nature and significance of chronic atrophic gastritis. Am. J. Dig. Dis. 18, 426 17 Vandelli C., Bottazzo G.F., Doniach D. & Franceschi F. (1979) Autoantibodies to gast~n-producing cells in antral (Type B) chronic gastritis. N. Engl. J. Med. 300, 1406 18 Wbitehead R. (1973) Mucosul Biopsy of the Gasfrointestinal Tract. W.B. Saunders, PA
43 (1989)
571-572
571
utoi R.M. KIRK Royal Free Hospital, London NW3 2OG, UK (Received
2 May
1989;
Gastric autoimmunity is well recognised in gastric atropy with associated pernicious anaemia-type A gastritis of Strickland and Mackay [16]. Autoantibodies to parietal cells also occur in some patients with Type R gastritis [I]. There is no proof that peptic ulcers have an autoimmune connection, but there is some circumstantial evidence to suggest this. If peptic ulcers in different sites are acknowledged to be related, then the damaged mucosa seen in gastritis associated particularly with gastric ulcer, and the parietal cell hyperplasia sometimes associated with duodenal ulcer evoke comp~son with autoimmune th~oiditis and autoimmune stimulation of the thyroid in “primary” thyrotoxicosis. Sirtori [14] in 1971 found plasma cells in biopsy specimens taken from duodenal ulcers at operation. Their endoplasmic reticulum was transformed into vesicles filled with proteinic material having a periodical structure of 200 A which he took be immunoglobulin A (IgA). He considered that the plasma cells might be an expression of a local autoimmune phenomenon brought about by ulcer-related antigens. In 1982 Rotter and Heiner (121 suggested that antibodies to secretory immunoglobulin may be over-represented in childhood duodenal ulcer subjects and allergic populations, leading to ulceration due to a deficiency in local mucosal immune defences. They also postulated that an immunoglobulin might be stimulatory to acid secretion. In 1979 Vandelli et al. [17] detected autoantibodies that reacted exclusively with gastrin producing (G) cells. De Lazzari et al. [2] also reported that immunoglobulin G (IgG), obtained from patients with duodenal ulcer stimulated gastric
accepted
24 June
1989)
acid secretion when injected into rats, by an action on the histamine receptors (H2-R}. It has been argued that gastric and duodenal ulcers form a continuum [5], with a small parietal cell area and low acid output in patients with proximal gastric ulcer, and an enlarged parietal cell area with normal or high acid output in patients with duodenal ulcer. In the ZollinerEllison syndrome the parietal cell area occupies virtually the whole stomach, the acid output is very high and the ulcers tend to be distally placed 191.Gastrin is not only stimulatory to acid output by parietal cells, but is trophic to them [4]. In gastric and duodenal ulcers the ulcer develops in mucosa damaged by gastritis or duodenitis [3, 4, 8, 13, 13. This is the area in which G cells are found and in gastritis with intestinal metaplasia, G cells are absent [lo, 151.Thus, peptic ulcers develop in a background of extension or retraction of the parietal cells and damage to the distal stomach and duodenal bulb-the area where G cells occur. Stimulation of the G cells would bring about extension of the parietal cell area as occurs in duodenal ulcer patients, and damage to them might produce the appearance of gastroduodenitis with sus~eptibili~ to acid attack and reduction of the trophic effect on the parietal cell area. This is very analogous to the immune mechanisms in the thyroid gland where destruction or stimulation of the parenchymal cells may occur, leading on the one hand to thyroiditis or on the other hand to thyrotoxicosis. Pathology of other paracrine glands may also be involved 1111. Thus, autoimmune mechanisms have been identified in some but by no means all peptic ulcer patients. The subject is worthy of further study 161.
572
R.&i. Kirk
Coghill N.E., Doniach D. & Roitt I.M. (1965) Autoantibodies in simple atrophic gastritis. Gut 6,48 De Lazzari F., Mirakian R., Venturi C., Bortalami M., Naccarato R., Doniach D. & Bottazzo G.F. (1985) Are there immunological forms of duodenal ulcer (DW) as a consequence of gastric parietal cell stimulating antobodies (PCS-Ab) ? Gut 26, Al 116 Gear M.W.L., Truelove S.C. ipt Whitehead R. (1971) Gastric ulcer and gastritis. Gut 12, 639 Johnson L.R. (1979) Regulation of gastrointestinal mucosal growth. WorldJ. Surg. 3, 477 Kirk R.M. (1981) Are gastric and duodenal ulcers separate diseases or do they form a continuum ? Big. Dis- Sci. 26, 149 Kirk RM. (1986) Could chronic peptic ulcers be localised areas of acid susceptibility generated by autoimmunity ? Lancet i, 772 Konjetzny GE. (1938) Der Mugenkrebs. Enke, Stuttgart Meikle D.D., Taylor K.B., Truelove SC. & Whitehead R. (1976) Gastritis, duodenitis, and eircuIating levels of gastrin in duodenal ulcers before and after vagotomy. Gur 17, 719 Neuberger P., Lewin M. & Bonlils S. (1972) Parietal and chief cell population in four cases of Zollinger-Ellison syndrome. Gastroenterulogy63, 937
10 Ottenjann R., Meiderer SE. Br Elster K. (1969) Forceps biopsy from the antrum, corpus and cardia of the stomach under endoscopic control. K&n. Wocherischr.47, 859 11 Polak J.M., Bloom S.R., Bishop A.E. 8c McCrossan M.V. (1978) D cell pathology in duodenal ulcers and achlorhydria. Metabolism 27 (suppl I), 1239 12 Rotter J.I. & Heiner DC. (1982) Are there immunologic forms of duodenal ulcer ? .I. C&n. Lab. Immrrnol. 7, 1 13 Schade R.O.K. (1966) Chronic gastritis. In : Recent Advances in Gastroenterology. Proc. World Congress of Gastroenterology, Tokyo, 2, 84 14 Sirtori L. (1971) Ulcer-related antigens ? Br. Med. J. 1, 403 15 Stadelmann O., Elster K. 8r Stoke M. (1971) The peptic gastric ulcer-histopathographic and functional investigations. &and. J. Gustroenterol.6, 613 16 Strickland R.G. dc Mackay I.R. (1973) A reappraisal of the nature and significance of chronic atrophic gastritis. Am. J. Dig. Dis. 18, 426 17 Vandelli C., Bottazzo G.F., Doniach D. & Franceschi F. (1979) Autoantibodies to gast~n-producing cells in antral (Type B) chronic gastritis. N. Engl. J. Med. 300, 1406 18 Wbitehead R. (1973) Mucosul Biopsy of the Gasfrointestinal Tract. W.B. Saunders, PA