TY - JOUR
T1 - Humoral and cellular responses to casein in patients with food protein–induced enterocolitis to cow's milk
AU - Caubet, Jean Christoph
AU - Bencharitiwong, Ramon
AU - Ross, Andrew
AU - Sampson, Hugh A.
AU - Berin, M. Cecilia
AU - Nowak-Węgrzyn, Anna
N1 - Publisher Copyright:
© 2016
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Background Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated food allergy manifesting within 1 to 4 hours of food ingestion with repetitive emesis and lethargy. Objective We sought to characterize immune responses to casein in children with FPIES caused by cow's milk (CM). Methods Total IgE and IgM, CM-specific IgG, and casein-specific IgE, IgG, IgG4, and IgM levels, as well as immunoglobulin free light chains, were measured in both patients with active and those with resolved CM-FPIES. Proliferating casein/T-effector cell counts were measured in children with CM-FPIES, children with IgE-mediated CM allergy, and those tolerating CM. Cytokine concentrations in the supernatants were quantified. Serum cytokine and tryptase levels were measured before and after a positive oral food challenge (OFC) result and compared with levels in those with a negative OFC result. Results We found low levels of CM and casein-specific IgG and casein-specific IgG4 in patients with CM-FPIES versus those tolerating CM (P < .05). Although we found both a high CD4+ T cell–proliferative response and TH2 cytokines production after casein stimulation in children with CM-FPIES, results were similar to those in control subjects. Significantly lower secretion of IL-10 and higher secretion of IL-9 by casein-stimulated T cells were found in patients with CM-FPIES versus those with IgE-mediated CM allergy. Lower baseline serum levels of IL-10 and higher tryptase levels were found in active CM-FPIES versus resolved CM-FPIES. We found a significant increase in serum IL-10 and IL-8 levels after a positive OFC result. Conclusions We confirm the paucity of humoral response in patients with CM-FPIES. IL-10 might play a key role in acquisition of tolerance in patients with CM-FPIES. Increased serum IL-8 levels in patients with active FPIES suggest neutrophil involvement. Elevated baseline serum tryptase levels in patients with active FPIES suggest low-grade intestinal mast cell activation or increased mast cell load.
AB - Background Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated food allergy manifesting within 1 to 4 hours of food ingestion with repetitive emesis and lethargy. Objective We sought to characterize immune responses to casein in children with FPIES caused by cow's milk (CM). Methods Total IgE and IgM, CM-specific IgG, and casein-specific IgE, IgG, IgG4, and IgM levels, as well as immunoglobulin free light chains, were measured in both patients with active and those with resolved CM-FPIES. Proliferating casein/T-effector cell counts were measured in children with CM-FPIES, children with IgE-mediated CM allergy, and those tolerating CM. Cytokine concentrations in the supernatants were quantified. Serum cytokine and tryptase levels were measured before and after a positive oral food challenge (OFC) result and compared with levels in those with a negative OFC result. Results We found low levels of CM and casein-specific IgG and casein-specific IgG4 in patients with CM-FPIES versus those tolerating CM (P < .05). Although we found both a high CD4+ T cell–proliferative response and TH2 cytokines production after casein stimulation in children with CM-FPIES, results were similar to those in control subjects. Significantly lower secretion of IL-10 and higher secretion of IL-9 by casein-stimulated T cells were found in patients with CM-FPIES versus those with IgE-mediated CM allergy. Lower baseline serum levels of IL-10 and higher tryptase levels were found in active CM-FPIES versus resolved CM-FPIES. We found a significant increase in serum IL-10 and IL-8 levels after a positive OFC result. Conclusions We confirm the paucity of humoral response in patients with CM-FPIES. IL-10 might play a key role in acquisition of tolerance in patients with CM-FPIES. Increased serum IL-8 levels in patients with active FPIES suggest neutrophil involvement. Elevated baseline serum tryptase levels in patients with active FPIES suggest low-grade intestinal mast cell activation or increased mast cell load.
KW - Food protein–induced enterocolitis syndrome
KW - T1 response
KW - T2 response
KW - T cells
KW - allergy
KW - food
KW - humoral response
KW - non–IgE-mediated
UR - http://www.scopus.com/inward/record.url?scp=84995961457&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2016.02.047
DO - 10.1016/j.jaci.2016.02.047
M3 - Article
C2 - 27545065
AN - SCOPUS:84995961457
SN - 0091-6749
VL - 139
SP - 572
EP - 583
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 2
ER -