title: Humoral immunity links Candida albicans infection and celiac disease.
abstract: OBJECTIVE
  The protein Hwp1, expressed on the pathogenic phase of Candida albicans, presents sequence analogy with the gluten protein gliadin and is also a substrate for transglutaminase. This had led to the suggestion that C. albicans infection (CI) may be a triggering factor for Celiac disease (CeD) onset. We investigated cross-immune reactivity between CeD and CI.
  
  
  METHODS
  Serum IgG levels against recombinant Hwp1 and serological markers of CeD were measured in 87 CeD patients, 41 CI patients, and 98 healthy controls (HC). IgA and IgG were also measured in 20 individuals from each of these groups using microchips sensitized with 38 peptides designed from the N-terminal of Hwp1.
  
  
  RESULTS
  CI and CeD patients had higher levels of anti-Hwp1 (p=0.0005 and p=0.004) and anti-gliadin (p=0.002 and p=0.0009) antibodies than HC but there was no significant difference between CeD and CI patients. CeD and CI patients had higher levels of anti-transglutaminase IgA than HC (p=0.0001 and p=0.0039). During CI, the increase in anti-Hwp1 paralleled the increase in anti-gliadin antibodies. Microchip analysis showed that CeD patients were more reactive against some Hwp1 peptides than CI patients, and that some deamidated peptides were more reactive than their native analogs. Binding of IgG from CeD patients to Hwp1 peptides was inhibited by γIII gliadin peptides.
  
  
  CONCLUSIONS
  Humoral cross-reactivity between Hwp1 and gliadin was observed during CeD and CI. Increased reactivity to Hwp1 deamidated peptide suggests that transglutaminase is involved in this interplay. These results support the hypothesis that CI may trigger CeD onset in genetically-susceptible individuals.
authors: Université Lille Nord de France, Lille, France; UDSL, Lille, France; Service des Maladies de l'Appareil Digestif et de la Nutrition, Lille, France.
authors: Marion
authors: M
authors: Corouge
authors: CHRU, Lille, France.
authors: Séverine
authors: S
authors: Loridant
authors: Université Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France.
authors: Chantal
authors: C
authors: Fradin
authors: Université Lille Nord de France, Lille, France; UDSL, Lille, France; EA2694, Lille, France; Pôle de Santé Publique Registre INSERM/InVS EPIMAD, Lille, France.
authors: Julia
authors: J
authors: Salleron
authors: INSERM U995, Lille, France.
authors: Sébastien
authors: S
authors: Damiens
authors: Departamento de Enfermeria 1, Escuela Universitaria de Enfermeria, Universidad del Pais Vasco, 48940 Leioa, Spain.
authors: Maria Dolores
authors: MD
authors: Moragues
authors: Innobiochips, 1 rue du Professeur Calmette, 59000 Lille, France.
authors: Vianney
authors: V
authors: Souplet
authors: Université Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France; CHRU, Lille, France.
authors: Thierry
authors: T
authors: Jouault
authors: Groupe d'Etude des Interactions Hôte-Pathogène, UPRES-EA 3142, Université d'Angers, Angers, France.
authors: Raymond
authors: R
authors: Robert
authors: CHRU, Lille, France; Institut d'Immunologie, Pôle de Biologie, Lille, France.
authors: Sylvain
authors: S
authors: Dubucquoi
authors: Université Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France; Service de Parasitologie Mycologie, Institut de Microbiologie, Lille, France; CHRU, Lille, France.
authors: Boualem
authors: B
authors: Sendid
authors: Service des Maladies de l'Appareil Digestif et de la Nutrition, Lille, France; Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors: Jean Fréderic
authors: JF
authors: Colombel
authors: Université Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France; Service de Parasitologie Mycologie, Institut de Microbiologie, Lille, France; CHRU, Lille, France.
authors: Daniel
authors: D
authors: Poulain
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000908:Antibodies, Fungal / Q000276:immunology / Q000302:isolation & purification; D015415:Biomarkers / Q000097:blood; D002176:Candida albicans / Q000502:physiology*; D002177:Candidiasis / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000382:microbiology*; D002446:Celiac Disease / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000382:microbiology*; D003429:Cross Reactions / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005453:Fluorescence; D005656:Fungal Proteins / Q000276:immunology; D005903:Gliadin / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D055815:Young Adult
chemical_list: D000908:Antibodies, Fungal; D015415:Biomarkers; D005656:Fungal Proteins; D010455:Peptides; D005903:Gliadin