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Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome.

Brown KL, Wekell P, Osla V, Sundqvist M, Sävman K, Fasth A, Karlsson A, Berg S - BMC Pediatr (2010)

Bottom Line: Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval.IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. kelly.brown@gu.se

ABSTRACT

Background: This study aimed to profile levels of blood cells and serum cytokines during afebrile and febrile phases of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to advance pathophysiological understanding of this pediatric disease.

Methods: A cohort of patients with a median age of 4.9 years experiencing 'typical PFAPA' episodes participated in this study. Blood cells and serum cytokines were analyzed by CBC analysis and multiplex ELISA.

Results: Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval. Relatively modest levels of pro-inflammatory cytokines were present in sera. IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.

Conclusions: Identification of dysregulated blood cells and serum cytokines is an initial step towards the identification of biomarkers of PFAPA disease and/or players in disease pathogenesis. Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.

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T-helper-associated cytokines and chemokines. The concentration (pg/ml) of (A) lymphocyte activator IL7 (left), Th17-associated cytokine IL17 (right) (B) Th2-associated cytokine IL4 and chemokine CCL11/Eotaxin (left and right respectively) and (C) Th1-associated cytokines and chemokines IFNγ (top left), MIG/CXCL9 (top right), and IP10/CXCL10 (bottom left) were measured in sera from controls (n = 3), afebrile patients (n = 3) and febrile patients ~15 hours after the onset of fever (n = 3) using a multiplex bead ELISA. Levels of IP10 were also assessed by a single-plex bead ELISA (C, bottom right) in controls (n = 13), afebrile patients (n = 8) and febrile patients 12 hours before, ~15 hours and ~120 hours after the onset of fever (-12 (n = 1), ~15 (n = 3), ~120 (n = 1)). Measured quantities are reported in Additional File 4, Table S3.
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Figure 4: T-helper-associated cytokines and chemokines. The concentration (pg/ml) of (A) lymphocyte activator IL7 (left), Th17-associated cytokine IL17 (right) (B) Th2-associated cytokine IL4 and chemokine CCL11/Eotaxin (left and right respectively) and (C) Th1-associated cytokines and chemokines IFNγ (top left), MIG/CXCL9 (top right), and IP10/CXCL10 (bottom left) were measured in sera from controls (n = 3), afebrile patients (n = 3) and febrile patients ~15 hours after the onset of fever (n = 3) using a multiplex bead ELISA. Levels of IP10 were also assessed by a single-plex bead ELISA (C, bottom right) in controls (n = 13), afebrile patients (n = 8) and febrile patients 12 hours before, ~15 hours and ~120 hours after the onset of fever (-12 (n = 1), ~15 (n = 3), ~120 (n = 1)). Measured quantities are reported in Additional File 4, Table S3.

Mentions: The presence of other pro-inflammatory cytokines was also investigated in sera by multiplex ELISA. The lymphocyte-specific cytokine, IL7, and CD4+ T-helper cytokine, IL17, were suppressed in both AFP and FP sera compared to controls (Figure 4A and Additional File 4, Table S3). IL17 is produced primarily by a subset of CD4+ T-helper-17 (Th17) cells. The activation of particular lymphocyte subsets, namely Th1, Th2 and Th17, is evident by the presence of particular cytokines that simultaneously drive one Th response while repressing others. The prototypic Th2 cytokine IL4 was present at comparable concentrations in AFP, FP and control sera. Concentrations of IL13, a Th2-associated cytokine, and CCL11/Eotaxin, a Th2-associated chemokine, were suppressed in sera from FP compared to controls (IL13) and AFP (IL13 and CCL11) sera (Figure 4B and Additional File 4, Table S3). The lower concentrations of these serum cytokines and IL17 suggested that neither a Th17- nor a Th2-type inflammatory response were active in FP sera.


Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome.

Brown KL, Wekell P, Osla V, Sundqvist M, Sävman K, Fasth A, Karlsson A, Berg S - BMC Pediatr (2010)

T-helper-associated cytokines and chemokines. The concentration (pg/ml) of (A) lymphocyte activator IL7 (left), Th17-associated cytokine IL17 (right) (B) Th2-associated cytokine IL4 and chemokine CCL11/Eotaxin (left and right respectively) and (C) Th1-associated cytokines and chemokines IFNγ (top left), MIG/CXCL9 (top right), and IP10/CXCL10 (bottom left) were measured in sera from controls (n = 3), afebrile patients (n = 3) and febrile patients ~15 hours after the onset of fever (n = 3) using a multiplex bead ELISA. Levels of IP10 were also assessed by a single-plex bead ELISA (C, bottom right) in controls (n = 13), afebrile patients (n = 8) and febrile patients 12 hours before, ~15 hours and ~120 hours after the onset of fever (-12 (n = 1), ~15 (n = 3), ~120 (n = 1)). Measured quantities are reported in Additional File 4, Table S3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2944328&req=5

Figure 4: T-helper-associated cytokines and chemokines. The concentration (pg/ml) of (A) lymphocyte activator IL7 (left), Th17-associated cytokine IL17 (right) (B) Th2-associated cytokine IL4 and chemokine CCL11/Eotaxin (left and right respectively) and (C) Th1-associated cytokines and chemokines IFNγ (top left), MIG/CXCL9 (top right), and IP10/CXCL10 (bottom left) were measured in sera from controls (n = 3), afebrile patients (n = 3) and febrile patients ~15 hours after the onset of fever (n = 3) using a multiplex bead ELISA. Levels of IP10 were also assessed by a single-plex bead ELISA (C, bottom right) in controls (n = 13), afebrile patients (n = 8) and febrile patients 12 hours before, ~15 hours and ~120 hours after the onset of fever (-12 (n = 1), ~15 (n = 3), ~120 (n = 1)). Measured quantities are reported in Additional File 4, Table S3.
Mentions: The presence of other pro-inflammatory cytokines was also investigated in sera by multiplex ELISA. The lymphocyte-specific cytokine, IL7, and CD4+ T-helper cytokine, IL17, were suppressed in both AFP and FP sera compared to controls (Figure 4A and Additional File 4, Table S3). IL17 is produced primarily by a subset of CD4+ T-helper-17 (Th17) cells. The activation of particular lymphocyte subsets, namely Th1, Th2 and Th17, is evident by the presence of particular cytokines that simultaneously drive one Th response while repressing others. The prototypic Th2 cytokine IL4 was present at comparable concentrations in AFP, FP and control sera. Concentrations of IL13, a Th2-associated cytokine, and CCL11/Eotaxin, a Th2-associated chemokine, were suppressed in sera from FP compared to controls (IL13) and AFP (IL13 and CCL11) sera (Figure 4B and Additional File 4, Table S3). The lower concentrations of these serum cytokines and IL17 suggested that neither a Th17- nor a Th2-type inflammatory response were active in FP sera.

Bottom Line: Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval.IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. kelly.brown@gu.se

ABSTRACT

Background: This study aimed to profile levels of blood cells and serum cytokines during afebrile and febrile phases of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to advance pathophysiological understanding of this pediatric disease.

Methods: A cohort of patients with a median age of 4.9 years experiencing 'typical PFAPA' episodes participated in this study. Blood cells and serum cytokines were analyzed by CBC analysis and multiplex ELISA.

Results: Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval. Relatively modest levels of pro-inflammatory cytokines were present in sera. IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.

Conclusions: Identification of dysregulated blood cells and serum cytokines is an initial step towards the identification of biomarkers of PFAPA disease and/or players in disease pathogenesis. Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.

Show MeSH
Related in: MedlinePlus