Mechanisms of allergy/immunology
Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling

https://doi.org/10.1016/j.jaci.2018.03.013Get rights and content

Background

In areas of high exposure to grass pollen, allergic patients are frequently sensitized to profilin, and some experience severe profilin-mediated food-induced reactions. This specific population of patients is ideal to study the relationship between respiratory and food allergies.

Objective

We sought to determine the role of oral mucosal epithelial barrier integrity in profilin-mediated allergic reactions.

Methods

Thirty-eight patients with profilin allergy stratified into mild or severe according to their clinical history and response to a profilin challenge test and 6 nonallergic subjects were recruited. Oral mucosal biopsies were used for measurement of CD11c, CD3, CD4, tryptase, claudin-1, occludin, E-cadherin, and vascular endothelial growth factor A levels; Masson trichrome staining; and POSTN, IL33, TPSAB, TPSB, and CMA gene expression analysis by using quantitative RT-PCR. Blood samples were used for basophil activation tests.

Results

Distinct features of the group with severe allergy included the following: (1) impaired epithelial integrity with reduced expression of claudin-1, occludin, and E-cadherin and decreased numbers of epithelial cells, which is indicative of acanthosis, higher collagen deposition, and angiogenesis; (2) inflammatory immune response in the mucosa, with an increased number of CD11c+ and CD4+ infiltrates and increased expression of the cytokine genes POSTN and IL33; and (3) a 10-fold increased sensitivity of basophils to profilin.

Conclusions

Patients with profilin allergy present with significant damage to the oral mucosal epithelial barrier, which might allow profilin penetration into the oral mucosa and induction of local inflammation. Additionally, severely allergic patients presented with increased sensitivity of effector cells.

Section snippets

Patients

Thirty-eight patients (18-58 years old) with a clinical history of suspected food allergies and 6 nonallergic subjects were included in the study. The patients were studied in the allergy departments of 4 hospitals: Hospital Universitario de La Princesa (Madrid, Spain), Hospital Universitario Clinico San Carlos (Madrid, Spain), Hospital HM Sanchinarro (Madrid, Spain), and Hospital Virgen del Puerto de Plasencia (Cáceres, Spain). All patients were subjected to a thorough interview to establish

Patients with severe profilin allergy show epithelial acanthosis, higher collagen fiber deposition, and increased angiogenesis in the oral mucosa

We aimed to analyze whether the oral mucosal barrier might be compromised, thus potentially facilitating access to the immunologic system of profilin and accounting for increased sensitivity to profilin. Hematoxylin and eosin staining, together with blind evaluation by 2 independent pathologists (Fig 1, A), showed significant thickening of the epithelium in the mild and severe allergy groups compared with nonallergic subjects (Fig 1, B). This epithelial deformation is called acanthosis, a

Discussion

Several lines of evidence show that the interaction between epithelial and immune cells in the mucosa is critical in the onset and maintenance of allergic inflammation.23 An intact functional mucosal barrier is considered crucial in the maintenance of airway homeostasis because it protects the host immune system from exposure to allergens and noxious environmental triggers.24 Epithelial cells in the mucosa, which were initially thought to be just inert barriers, are now considered part of the

References (42)

  • M.C. Berin et al.

    Mucosal immunology of food allergy

    Curr Biol

    (2013)
  • N. Novak et al.

    The immune privilege of the oral mucosa

    Trends Mol Med

    (2008)
  • M.F. Gurish et al.

    Developmental origin and functional specialization of mast cell subsets

    Immunity

    (2012)
  • I. Waern et al.

    Mast cell chymase modulates IL-33 levels and controls allergic sensitization in dust-mite induced airway inflammation

    Mucosal Immunol

    (2013)
  • J. Saarinen et al.

    Activation of human interstitial procollagenase through direct cleavage of the Leu83-Thr84 bond by mast cell chymase

    J Biol Chem

    (1994)
  • M.W. Kofford et al.

    Cleavage of type I procollagen by human mast cell chymase initiates collagen fibril formation and generates a unique carboxyl-terminal propeptide

    J Biol Chem

    (1997)
  • E. Kakizoe et al.

    Isoform-selective upregulation of mast cell chymase in the development of skin fibrosis in scleroderma model mice

    J Invest Dermatol

    (2001)
  • D. Barber et al.

    Challenges for allergy diagnosis in regions with complex pollen exposures

    Curr Allergy Asthma Rep

    (2015)
  • D. Barber et al.

    Component-resolved diagnosis of pollen allergy based on skin testing with profilin, polcalcin and lipid transfer protein pan-allergens

    Clin Exp Allergy

    (2009)
  • R. Asero et al.

    Prevalence and clinical relevance of IgE sensitization to profilin in childhood: a multicenter study

    Int Arch Allergy Immunol

    (2015)
  • C. Mastrorilli et al.

    Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification

    Allergy

    (2016)
  • Cited by (35)

    • Novel murine mAbs define specific and cross-reactive epitopes on the latex profilin panallergen Hev b 8

      2020, Molecular Immunology
      Citation Excerpt :

      Profilins are relevant allergens in pollen, plant foods, and latex allergies. A proportion of patients sensitized to profilin present both respiratory and food allergies, especially in areas of high exposure to grass or some tree pollens (Rosace et al., 2019). Profilins are a family of highly conserved proteins present in all eukaryotic cells.

    • Organ-specific allergen challenges in airway allergy: Current utilities and future directions

      2023, Allergy: European Journal of Allergy and Clinical Immunology
    • Deciphering the role of platelets in severe allergy by an integrative omics approach

      2023, Allergy: European Journal of Allergy and Clinical Immunology
    View all citing articles on Scopus

    Supported by ISCIII (project nos. PI16/00249 and PI15/02256) by ISCIII, which was cofounded by FEDER, for the thematic network and cooperative research centers ARADyAL (RD16/0006/0015 and RD16/0006/0009). D.R. was supported by FPI-CEU predoctoral fellowships.

    Disclosure of potential conflict of interest: M. Fernandez-Rivas received grants from the European Commission and the Spanish Government (ISCIII MINECO, grant no. P116/00249; ARADyAL, RD16/0006/099) and received consultant and personal support fees from Aimmune; personal fees from DBV (DSMV Member), Schrieber Foods, and Allergy Therapeutics; and meeting organization and speakers' fees from the Fundacion SEAICySMCL. D. Barber received grants from Instituto de Salud Carlos III and personal fees from ALK-Abelló and Aimmune outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.

    View full text