title: Raised immunoglobulin A and circulating T follicular helper cells are linked to the development of food allergy in paediatric liver transplant patients.
abstract: BACKGROUND
  Post-transplant food allergy (LTFA) is increasingly observed after paediatric liver transplantation (LT). Although the immunopathology of LTFA remains unclear, immunoglobulin (Ig) E seems to be implicated.
  
  
  OBJECTIVE
  To study humoral and cellular immunity in paediatric LT patients in search for factors associated with LTFA, and compare with healthy controls (HC) and non-transplant food-allergic children (FA).
  
  
  METHODS
  We studied serum Ig levels in 29 LTFA, 43 non-food-allergic LT patients (LTnoFA), 21 FA patients and 36 HC. Serum-specific IgA and IgE against common food allergens in LTFA, IgA1 , IgA2 and joining-chain-containing polymeric IgA (pIgA) were measured. Peripheral blood mononuclear cells were analysed by flow cytometry for B and T cell populations of interest.
  
  
  RESULTS
  Serum IgA and specific IgA were higher in LTFA compared to LTnoFA. LTFA patients had the highest proportion of circulating T follicular helper cells (cTfh). The percentage of cTfh correlated positively with serum IgA. Unique in LTFA was also the significant increase in serum markers of mucosal IgA and the decrease in the Th17 subset of CXCR5(-) CD4(+) cells compared to HC. Both LT patients exhibited a rise in IgA(+) memory B cells and plasmablasts compared to HC and FA.
  
  
  CONCLUSIONS
  LT has an impact on humoral immunity, remarkably in those patients developing FA. The increase in serum markers of mucosal IgA, food allergen-specific IgA and cTfh cells observed in LTFA, point towards a disturbance in intestinal immune homoeostasis in this patient group.
authors.affiliation: Department of Pediatric Gastroenterology, Hepatology and Nutrition, Princess Elisabeth Children's Hospital, Ghent University Hospital, Ghent, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: De Bruyne
authors.affiliation: Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Gevaert
authors.affiliation: Department of Pediatric Gastroenterology, Hepatology and Nutrition, Princess Elisabeth Children's Hospital, Ghent University Hospital, Ghent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Van Winckel
authors.affiliation: Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: De Ruyck
authors.affiliation: Department of Pediatrics, Princess Elisabeth Children's Hospital, Ghent University Hospital, Ghent, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Minne
authors.affiliation: Department of Pediatrics, Princess Elisabeth Children's Hospital, Ghent University Hospital, Ghent, Belgium.|Clinical Immunology Research Laboratory, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Bogaert
authors.affiliation: Department of Pediatric Gastroenterology, Hepatology and Nutrition, Princess Elisabeth Children's Hospital, Ghent University Hospital, Ghent, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Van Biervliet
authors.affiliation: Department of Pediatric Gastroenterology, Hepatology and Nutrition, Princess Elisabeth Children's Hospital, Ghent University Hospital, Ghent, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Vande Velde
authors.affiliation: Service de Gastro-entérologie et Hépatologie Pédiatrique et Institut de Recherche Expérimentale et Clinique, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Smets
authors.affiliation: Service de Gastro-entérologie et Hépatologie Pédiatrique et Institut de Recherche Expérimentale et Clinique, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Sokal
authors.affiliation: Inserm U995, Faculty of Medicine, CIC-PT-9301, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Jeanne de Flandre, CHRU Lille, University Lille2, Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Gottrand
authors.affiliation: Centre d'Investigation Clinique de Lille-PT-1403-Inserm-CH&U, Inserm U995, Faculty of Medicine, University Lille2, Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Vanhelst
authors.affiliation: Pole of Pneumology, ENT and Dermatology, Institute of Experimental and Clinical Research, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.|Walloon Excellence in Lifesciences and Biotechnology (WELBIO) Institute, Brussels, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Detry
authors.affiliation: Pole of Pneumology, ENT and Dermatology, Institute of Experimental and Clinical Research, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.|Walloon Excellence in Lifesciences and Biotechnology (WELBIO) Institute, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Pilette
authors.affiliation: Clinical Immunology Research Laboratory, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.|Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium.|Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: B N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Clinical Immunology Research Laboratory, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Dullaers
mesh_terms: D000293:Adolescent; D000367:Age Factors; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D005260:Female; D005512:Food Hypersensitivity / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D007223:Infant; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; C034639:polymeric IgA; D007073:Immunoglobulin E
keywords: T follicular helper cells; children; food allergy; immunoglobulin A; liver transplantation; polymeric IgA; regulatory T cells; secretory IgA; specific IgA