title: Molecular spreading and predictive value of preclinical IgE response to Phleum pratense in children with hay fever.
abstract: BACKGROUND
  IgE sensitization against grass pollen is a cause of seasonal allergic rhinitis.
  
  
  OBJECTIVE
  We sought to investigate the evolution at the molecular level and the preclinical predictive value of IgE responses against grass pollen.
  
  
  METHODS
  The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was administered yearly, and blood samples were collected at 1, 2, 3, 5, 6, 7, 10, and 13 years of age. Grass pollen-related seasonal allergic rhinitis (SARg) was diagnosed according to nasal symptoms in June/July. Serum IgE antibodies to Phleum pratense extract and 8 P pratense molecules were tested with immune-enzymatic singleplex and multiplex assays, respectively.
  
  
  RESULTS
  One hundred seventy-seven of the 820 examined children had SARg. A weak monomolecular/oligomolecular IgE response to P pratense was observed very frequently before SARg onset. These initial IgE responses increased in concentration and molecular complexity during the preclinical and clinical process. A typical progression of IgE sensitization was observed: Phl p 1 (initiator in >75% of cases); then Phl p 4 and Phl p 5; then Phl p 2, Phl p 6, and Phl p 11; and then Phl p 12 and Phl p 7. At age 3 years, IgE sensitization predicted SARg by age 12 years (positive predictive value, 68% [95% CI, 50% to 82%]; negative predictive value, 84% [95% CI, 80% to 87%]). At this preclinical prediction time, the number of recognized molecules and the serum levels of IgE to P pratense were significantly lower than at 3 or more years after SARg onset.
  
  
  CONCLUSIONS
  The IgE response against grass pollen molecules can start years before disease onset as a weak monosensitization or oligosensitization phenomenon. It can increase in serum concentration and complexity through a "molecular spreading" process during preclinical and early clinical disease stages. Testing IgE sensitization at a preclinical stage facilitates prediction of seasonal allergic rhinitis at its molecular monosensitization or oligosensitization stage.
authors: Department of Paediatric Pneumology and Immunology, Charité University Medical Centre, Berlin, Germany.
authors: Laura
authors: L
authors: Hatzler
authors: Valentina
authors: V
authors: Panetta
authors: Susanne
authors: S
authors: Lau
authors: Petra
authors: P
authors: Wagner
authors: Renate L
authors: RL
authors: Bergmann
authors: Sabina
authors: S
authors: Illi
authors: Karl E
authors: KE
authors: Bergmann
authors: Thomas
authors: T
authors: Keil
authors: Stephanie
authors: S
authors: Hofmaier
authors: Alexander
authors: A
authors: Rohrbach
authors: Carl Peter
authors: CP
authors: Bauer
authors: Ute
authors: U
authors: Hoffman
authors: Johannes
authors: J
authors: Forster
authors: Fred
authors: F
authors: Zepp
authors: Antje
authors: A
authors: Schuster
authors: Ulrich
authors: U
authors: Wahn
authors: Paolo Maria
authors: PM
authors: Matricardi
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007223:Infant; D008297:Male; D031784:Phleum / Q000276:immunology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*
chemical_list: D007073:Immunoglobulin E