Humoral immunity links Candida albicans infection and celiac disease

PLoS One. 2015 Mar 20;10(3):e0121776. doi: 10.1371/journal.pone.0121776. eCollection 2015.


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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Fungal / immunology
  • Antibodies, Fungal / isolation & purification
  • Biomarkers / blood
  • Candida albicans / physiology*
  • Candidiasis / blood
  • Candidiasis / complications
  • Candidiasis / immunology*
  • Candidiasis / microbiology*
  • Celiac Disease / blood
  • Celiac Disease / complications
  • Celiac Disease / immunology*
  • Celiac Disease / microbiology*
  • Cross Reactions / immunology
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescence
  • Fungal Proteins / immunology
  • Gliadin / immunology
  • Humans
  • Immunity, Humoral*
  • Immunoblotting
  • Male
  • Middle Aged
  • Peptides / immunology
  • Young Adult


  • Antibodies, Fungal
  • Biomarkers
  • Fungal Proteins
  • Peptides
  • Gliadin

Grants and funding

This work received the following grant support: Unit U995-2 INSERM- Lille2 University; the European Community’s 7th Framework program (FP7-2007-2013) grant agreement N° Health F2-2010-260338 (ALLFUN); Digest Science Foundation. Co-author VS is affiliated to Innobiochips. Innobiochips provided support in the form of salary for author VS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Innobiochips played an indirect role through the participation of the co-author VS. The specific role of this author is articulated in the ‘author contributions’ section.