title: Duration of clinical reactivity in cow's milk allergy is associated with levels of specific immunoglobulin G4 and immunoglobulin A antibodies to beta-lactoglobulin.
abstract: BACKGROUND
  The development of tolerance in IgE-mediated allergies has been associated with lower cow's milk (CM)-specific IgE levels, increasing levels of specific IgG4 and, more contestably, IgA.
  
  
  OBJECTIVE
  We investigated whether specific antibody responses to CM proteins differ over time between patients who recovered from cow's milk allergy (CMA) by the age of 3 years and those who developed tolerance only after the age of 8 years.
  
  
  METHODS
  The study population comprised of 83 patients with IgE-mediated CMA. They belonged to a cohort of 6209 healthy, full-term infants followed prospectively for the emergence of CMA. Serum samples were available at diagnosis (median age 7 months), 1 year later (median 19 months) and at follow-up (median 8.5 years). Age-matched control subjects with no history of CMA (n=76) participated in the follow-up. Serum levels of IgE antibodies to CM were measured using UniCAP. Levels of IgA, IgG1 and IgG4 antibodies to beta-lactoglobulin and alpha-casein were measured using ELISA.
  
  
  RESULTS
  Patients with persistent CMA at the age of 8 years (n=18 at diagnosis, n=16 at later time-points) had higher CM-specific IgE levels at all three time-points (P<0.001) compared with patients who became tolerant by 3 years (n=55 at diagnosis, n=54 a year later, n=40 at follow-up). They had lower serum IgA levels to beta-lactoglobulin at diagnosis (P=0.01), and lower IgG4 levels to beta-lactoglobulin (P=0.04) and alpha-casein (P=0.05) at follow-up.
  
  
  CONCLUSIONS
  High CM-specific IgE levels predict the persistence of CMA. Development of tolerance is associated with elevated levels of beta-lactoglobulin-specific serum IgA at the time of diagnosis, and later increasing specific IgG4 levels to beta-lactoglobulin and alpha-casein.
authors: Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. erkki.savilahti@hus.fi
authors: E M
authors: EM
authors: Savilahti
authors: K M
authors: KM
authors: Saarinen
authors: E
authors: E
authors: Savilahti
mesh_terms: D000375:Aging / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007167:Immunotherapy; D007782:Lactoglobulins / Q000276:immunology*; D016269:Milk Hypersensitivity / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007782:Lactoglobulins; D007073:Immunoglobulin E