title: A Cross-Sectional Study of the Prevalence of Gastrointestinal Symptoms and Pathology in Patients With Common Variable Immunodeficiency.
abstract: The objective of this study was to study the prevalence of gastrointestinal (GI) symptoms and histopathology in patients with common variable immunodeficiency (CVID) as well as linking the findings to GI infections and markers of systemic immune activation.
  
  
  
  In this cross-sectional study, we addressed GI symptoms in 103 patients and GI histopathological findings in 53 patients who underwent upper and lower endoscopic examination. The most frequent histopathological findings were linked to GI symptoms, B-cell phenotype, and markers of systemic immune activation (soluble (s)CD14, sCD25, and sCD163). Microarray analysis compared "celiac-like disease" in CVID to celiac disease. Screening for selected bacterial and viral infections in fecal samples and gut mucosal biopsies was performed.
  
  
  
  The main findings of this study were as follows: most common GI symptoms were bloating (34%), pain (30%), and diarrhea (26%). The most frequent histopathological findings were increased intraepithelial lymphocytes in the descending part of the duodenum, i.e., "celiac-like disease" (46% of patients), decreased numbers of plasma cells in GI tract mucosa (62%), and lymphoid hyperplasia (38%), none of which were associated with GI symptoms. Reduced plasma cells in GI mucosa were associated with B-cell phenotypic characteristics of CVID, and increased serum levels of sCD14 (P=0.025), sCD25 (P=0.01), and sCD163 (P=0.04). Microarray analyses distinguished between CVID patients with "celiac-like disease" and celiac disease. Positive tests for bacterial and viral infections were scarce both in fecal samples and gut mucosal biopsies, including PCR test for norovirus in biopsy specimens (0 positive tests).
  
  
  
  In conclusion, GI pathology is common in CVID, but does not necessarily cause symptoms. However, reduced plasma cells in GI mucosa were linked to systemic immune activation, "celiac-like disease" in CVID and true celiac disease appear to be different disease entities, as assessed by gene expression, and infections (including norovirus) are rarely a cause of the CVID enteropathy.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.|K. G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Silje F
authors.initials: SF
authors.lastname: Jørgensen
authors.affiliation: Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Henrik M
authors.initials: HM
authors.lastname: Reims
authors.affiliation: Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Didrik
authors.initials: D
authors.lastname: Frydenlund
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Holm
authors.affiliation: Department of Transplantation Medicine, Section of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Vemund
authors.initials: V
authors.lastname: Paulsen
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Annika E
authors.initials: AE
authors.lastname: Michelsen
authors.affiliation: Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Jørgensen
authors.affiliation: Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Liv T
authors.initials: LT
authors.lastname: Osnes
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Jorunn
authors.initials: J
authors.lastname: Bratlie
authors.affiliation: Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Tor J
authors.initials: TJ
authors.lastname: Eide
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Christen P
authors.initials: CP
authors.lastname: Dahl
authors.affiliation: Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Ellen
authors.initials: E
authors.lastname: Holter
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Rune R
authors.initials: RR
authors.lastname: Tronstad
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Kurt
authors.initials: K
authors.lastname: Hanevik
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Hans-Richard
authors.initials: HR
authors.lastname: Brattbakk
authors.affiliation: Medical Genetics Department, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Kaveh
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Torunn
authors.initials: T
authors.lastname: Fiskerstrand
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Microbiology, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Anne-Marte B
authors.initials: AB
authors.lastname: Kran
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|K. G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.|K. G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Transplantation Medicine, Section of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Centre for Immune Regulation, University of Oslo, Oslo, Norway.
authors.forename: Knut E A
authors.initials: KE
authors.lastname: Lundin
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Børre
authors.initials: B
authors.lastname: Fevang
mesh_terms: D015746:Abdominal Pain / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology; D002446:Celiac Disease / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003113:Colonoscopy; D017074:Common Variable Immunodeficiency / Q000453:epidemiology* / Q000276:immunology; D003248:Constipation / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D003430:Cross-Sectional Studies; D003967:Diarrhea / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D004386:Duodenum / Q000473:pathology; D016145:Endoscopy, Digestive System; D000071041:Esophageal Mucosa / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D041981:Gastrointestinal Tract / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology; D015995:Prevalence; D059467:Transcriptome; D055815:Young Adult