title: Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.
abstract: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens.
  
  
  
  We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population.
  
  
  
  PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit.
  
  
  
  In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.
authors.affiliation: Pediatric Department, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria, University of Parma, Parma, Italy.|Department of Pediatric Pneumology and Immunology, Charité Medical University, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Mastrorilli
authors.affiliation: Pediatric Department and Pediatric Allergology Unit, Sandro Pertini Hospital, Rome.
authors.forename: S
authors.initials: S
authors.lastname: Tripodi
authors.affiliation: Pediatric Department, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria, University of Parma, Parma, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Caffarelli
authors.affiliation: Department of Pediatric Pneumology and Immunology, Charité Medical University, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Perna
authors.affiliation: Pediatric Department and Pediatric Allergology Unit, Sandro Pertini Hospital, Rome.
authors.forename: A
authors.initials: A
authors.lastname: Di Rienzo-Businco
authors.affiliation: Pediatric Department and Pediatric Allergology Unit, Sandro Pertini Hospital, Rome.
authors.forename: I
authors.initials: I
authors.lastname: Sfika
authors.affiliation: Allergology Service, San Carlo Clinic, Paderno Dugnano, Milan.
authors.forename: R
authors.initials: R
authors.lastname: Asero
authors.affiliation: Pediatric Unit, Department for Mother and Child, Ramazzini Hospital, Carpi.
authors.forename: A
authors.initials: A
authors.lastname: Dondi
authors.affiliation: Pediatric Unit, Mazzoni Hospital, Ascoli Piceno.
authors.forename: A
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: Pediatric Department, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria, University of Parma, Parma, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Povesi Dascola
authors.affiliation: Pediatric Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna.
authors.forename: G
authors.initials: G
authors.lastname: Ricci
authors.affiliation: Pediatric Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna.
authors.forename: F
authors.initials: F
authors.lastname: Cipriani
authors.affiliation: Pediatric Department, Second University, Naples.
authors.forename: N
authors.initials: N
authors.lastname: Maiello
authors.affiliation: Pediatric Department, Second University, Naples.
authors.forename: M
authors.initials: M
authors.lastname: Miraglia Del Giudice
authors.affiliation: Pediatric Department, La Sapienza University, Rome.
authors.forename: T
authors.initials: T
authors.lastname: Frediani
authors.affiliation: Pediatric Department, La Sapienza University, Rome.
authors.forename: S
authors.initials: S
authors.lastname: Frediani
authors.affiliation: Pediatric Department, La Sapienza University, Rome.
authors.forename: F
authors.initials: F
authors.lastname: Macrì
authors.affiliation: Pediatric Department, La Sapienza University, Rome.
authors.forename: C
authors.initials: C
authors.lastname: Pistoletti
authors.affiliation: Pediatric Unit, Fatebenefratelli Hospital, Benevento.
authors.forename: I
authors.initials: I
authors.lastname: Dello Iacono
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan.
authors.forename: M F
authors.initials: MF
authors.lastname: Patria
authors.affiliation: Pediatric Intermediate Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan.
authors.forename: E
authors.initials: E
authors.lastname: Varin
authors.affiliation: Pediatric Section, Department of Life and Reproduction Sciences, University of Verona, Verona.
authors.forename: D
authors.initials: D
authors.lastname: Peroni
authors.affiliation: Pediatric Section, Department of Life and Reproduction Sciences, University of Verona, Verona.
authors.forename: P
authors.initials: P
authors.lastname: Comberiati
authors.affiliation: Pediatric Department, Policlinico of Tor Vergata, Tor Vergata University, Rome.
authors.forename: L
authors.initials: L
authors.lastname: Chini
authors.affiliation: Pediatric Department, Policlinico of Tor Vergata, Tor Vergata University, Rome.
authors.forename: V
authors.initials: V
authors.lastname: Moschese
authors.affiliation: Pediatric Department, La Sapienza University, Rome.
authors.forename: S
authors.initials: S
authors.lastname: Lucarelli
authors.affiliation: Pediatric Unit, San Giuseppe Hospital, Empoli.
authors.forename: R
authors.initials: R
authors.lastname: Bernardini
authors.affiliation: Pediatric Unit, Grassi Hospital, Rome.
authors.forename: G
authors.initials: G
authors.lastname: Pingitore
authors.affiliation: Pediatric Unit, Santa Barbara Hospital, Iglesias.
authors.forename: U
authors.initials: U
authors.lastname: Pelosi
authors.affiliation: Pulmonary Disease and Allergy Unit, G. Gaslini Hospital, Genoa.
authors.forename: R
authors.initials: R
authors.lastname: Olcese
authors.affiliation: Pediatric Department, La Sapienza University, Rome.
authors.forename: M
authors.initials: M
authors.lastname: Moretti
authors.affiliation: Pediatric Unit, San Giovanni di Dio Hospital, Crotone.
authors.forename: A
authors.initials: A
authors.lastname: Cirisano
authors.affiliation: Department of Laboratory Medicine, University of Padua, Padua.
authors.forename: D
authors.initials: D
authors.lastname: Faggian
authors.affiliation: Pediatric Department, Policlinico of Tor Vergata, Tor Vergata University, Rome.
authors.forename: A
authors.initials: A
authors.lastname: Travaglini
authors.affiliation: Department of Laboratory Medicine, University of Padua, Padua.
authors.forename: M
authors.initials: M
authors.lastname: Plebani
authors.affiliation: Pediatric Unit, Fatebenefratelli Hospital, Benevento.|Primary Care Pediatrics, ASL Salerno, Rome.
authors.forename: M C
authors.initials: MC
authors.lastname: Verga
authors.affiliation: UOC Pediatria, San Camillo Forlanini, Rome.
authors.forename: M
authors.initials: M
authors.lastname: Calvani
authors.affiliation: Department of Statistical Sciences, Sapienza University of Rome, Rome.
authors.forename: P
authors.initials: P
authors.lastname: Giordani
authors.affiliation: Department of Pediatric Pneumology and Immunology, Charité Medical University, Berlin, Germany.
authors.forename: P M
authors.initials: PM
authors.lastname: Matricardi
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000485:Allergens / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D015897:Comorbidity; D003233:Conjunctivitis, Allergic / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D005260:Female; D005502:Food / Q000009:adverse effects*; D005512:Food Hypersensitivity / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007558:Italy / Q000453:epidemiology; D008297:Male; D011058:Pollen / Q000276:immunology*; D011159:Population Surveillance; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D012307:Risk Factors; D012621:Seasons; D012882:Skin Tests; D013577:Syndrome
chemical_list: D000485:Allergens; D007073:Immunoglobulin E
keywords: allergic rhinoconjunctivitis; children; classification; cluster analysis; endotypes; molecules; oral allergy syndrome; panallergens; pollen-food syndrome