title: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy syndrome is associated with activation of GM-CSF and burst-like expression of IL-8 in peripheral blood.
abstract: BACKGROUND
  Periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy (PFAPA) is an autoinflammatory syndrome characterized by periodic fever with aphthous stomatitis, cervical lymphadenopathy, myalgia, and abdominal pain. Peripheral blood concentrations of selected cytokines of PFAPA patients during and between febrile episodes were analyzed in a search for PFAPA-specific molecular signature.
  
  
  METHODS
  23 children with PFAPA (age 6.07 ± 2.94 years, range 5-9 years) and three control children with severe oropharyngeal infections (age 6.2 ± 7.95 years, range 1-17 years) participated in the study. Peripheral blood concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, GM-CSF, TNF-α were measured using Luminex technology.
  
  
  RESULTS
  PFAPA febrile episodes were characterized by detection of GM-CSF - 134.07 ± 315.5 pg/mL; significant (P < 0.001), compared to baseline and controls, elevation of concentrations of IL-8 (3193.7 ± 2508 pg/mL vs. 100.36 ± 119. pg/mL vs. 2.04 ± 4.08 pg/mL, respectively), IL-6 (1355.38 ± 2026.53 pg/mL vs. 28.8 ± 44.2 pg/mL and 27.13 ± 26.42 pg/mL, respectively). IL-1β was detected only in febrile and afebrile PFAPA patients (922.8 ± 1639 pg/mL vs. 10.98 ± 19.4 pg/ml, P < 0.002, respectively), but not in controls. Peripheral blood concentration of TNFα did not differ significantly between study groups. IL-2, IL-4, IL-5, and IL-10 were negligible in all study subjects.
  
  
  CONCLUSIONS
  PFAPA febrile episodes are characterized by activation of GM-CSF and IL-8 with Th1 skewing. We propose a molecular mechanism governing this phenomenon.
authors.affiliation: Pediatrics Department B, Saban Pediatric Medical Center , Beer Sheva , Israel.
authors.forename: Eduard
authors.initials: E
authors.lastname: Ling
authors.forename: Moshe
authors.initials: M
authors.lastname: Israeli
authors.forename: Tirza
authors.initials: T
authors.lastname: Klein
authors.forename: Jacob
authors.initials: J
authors.lastname: Amir
authors.forename: Liora
authors.initials: L
authors.lastname: Harel
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D005260:Female; D005334:Fever / Q000097:blood*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D010612:Pharyngitis / Q000097:blood*; D013281:Stomatitis, Aphthous / Q000097:blood*; D013577:Syndrome
chemical_list: D016207:Cytokines; D016209:Interleukin-8; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Cytokines; GM-CSF; IL-8; Inflammation; PFAPA