title: The role of casein-specific IgA and TGF-β in children with food protein-induced enterocolitis syndrome to milk.
abstract: BACKGROUND
  Food protein-induced enterocolitis syndrome (FPIES) is a gastrointestinal hypersensitivity disorder with a poorly understood pathophysiology and no biomarkers to aid in diagnosis.
  
  
  OBJECTIVE
  To investigate humoral and cellular responses to casein in children with milk-FPIES, including the role of casein-specific (cs) IgA and T-cell mediated TGF-β responses.
  
  
  METHODS
  Thirty-one children previously diagnosed with milk-FPIES were challenged with milk. Twelve age-matched children with FPIES to other foods and 6 milk-tolerant children without a history of FPIES were used as controls. Casein-specific IgE, IgG, IgG4, and IgA were measured in serum and TGF-β levels in supernatants of casein-stimulated PBMCs.
  
  
  RESULTS
  Twenty-six children with milk-FPIES reacted (active milk-FPIES) and five tolerated milk (milk-FPIES resolved) during food challenge. All of them had significantly lower levels of csIgG, csIgG4, and csIgA than control children (p-value<0.001). There were no TGF-β responses in supernatants of active milk-FPIES children.
  
  
  CONCLUSIONS
  Children with milk-FPIES have low levels of csIgG, csIgG4, and csIgA. In particular, children with active FPIES to cow's milk have deficient T-cell mediated TGF-β responses to casein, rendering TGF-β a promising biomarker in identifying children who are likely to experience FPIES reactions to this allergen. Prospective studies are needed to validate these findings, elucidate their role in FPIES pathophysiology, and establish the diagnostic utility of TGF-β in milk-induced FPIES.
authors.affiliation: Division of Allergy & Immunology and The Jaffe Food Allergy Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Allergy and Clinical Immunology, 424 General Military Training Hospital, Thessaloniki, Greece.
authors.forename: George N
authors.initials: GN
authors.lastname: Konstantinou
authors.forename: Ramon
authors.initials: R
authors.lastname: Bencharitiwong
authors.forename: Alexander
authors.initials: A
authors.lastname: Grishin
authors.forename: Jean-Christoph
authors.initials: JC
authors.lastname: Caubet
authors.forename: Luda
authors.initials: L
authors.lastname: Bardina
authors.forename: Scott H
authors.initials: SH
authors.lastname: Sicherer
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Sampson
authors.forename: Anna
authors.initials: A
authors.lastname: Nowak-Węgrzyn
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002364:Caseins / Q000276:immunology; D002417:Cattle; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004760:Enterocolitis / Q000209:etiology / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D008892:Milk / Q000009:adverse effects / Q000276:immunology; D016269:Milk Hypersensitivity / Q000150:complications / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000485:Allergens; D015415:Biomarkers; D002364:Caseins; D007070:Immunoglobulin A; D016212:Transforming Growth Factor beta; D007073:Immunoglobulin E
keywords: IgA; IgG4; PBMCs; TGF-β; casein; food challenge; immunoglobulin A; milk allergy; peripheral blood mononuclear cell; transforming growth factor β