title: Chronic active gastritis in X-linked lymphoproliferative disease.
abstract: Gastric lesions in primary constitutive immune deficiencies include multifocal atrophic gastritis, erosive pangastritis, and a pattern of gastric lesions reminiscent of graft-versus-host disease. We describe the genetic anomalies in 2 monozygotic twins with an X-linked lymphoproliferative disease (XLP; MIM 308240), a rare familial setting of high susceptibility to Epstein-Barr virus (EBV). Since early childhood, both twin brothers exhibited a severe chronic active atrophic pangastritis. A germline screening of the SH2D1A (MIM 300490) and BIRC4 (MIM 300079) genes was performed, and also a high-resolution whole-genome SNP profiling (Infinium Sentrix Human-1 Genotyping BeadChip, Illumina). A 3 Megabase deletion in the Xq25 region, encompassing the SH2D1A gene, was defined by SNP array genotyping. Histologic analysis of yearly or twice yearly gastric biopsies in both children showed a Helicobacter pylori-negative, Epstein-Barr virus-negative chronic active atrophic pangastritis, with superficial ulcer formation, foveolar hyperplasia, glandular dilatation and ultimately pseudopyloric and intestinal metaplasia. No such chronic active inflammatory gastric lesions have been reported to date in XLP. The similarities between XLP and common variable immunodeficiency (MIM 240500) underscore the need for early recognition and close monitoring of these gastric lesions, with special regard to their neoplastic potential. No infectious cause was determined. We favor a dysimmune mechanism in the development of this chronic atrophic gastritis, presenting a striking similarity to the recently described atrophic autoimmune pangastritis.
authors.affiliation: Department of Pathology, CHU Sainte-Justine, Université de Montréal, Québec, Canada.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Rougemont
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Fournet
authors.forename: Steven R
authors.initials: SR
authors.lastname: Martin
authors.forename: Geneviève
authors.initials: G
authors.lastname: de Saint-Basile
authors.forename: Sylvain
authors.initials: S
authors.lastname: Latour
authors.forename: Marie-Noël
authors.initials: MN
authors.lastname: Primeau
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: Elie
authors.initials: E
authors.lastname: Haddad
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
mesh_terms: D000293:Adolescent; D041321:Chromosomes, Human, X; D002908:Chronic Disease; D004200:Diseases in Twins / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005756:Gastritis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000473:pathology; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D014430:Twins, Monozygotic
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein