The Impact of Cystic Fibrosis on the Immunologic Profile of Pediatric Patients

Bernardi, Daniela Miotto; Ribeiro, Antonio Fernando; Mazzola, Taís Nitsch; Vilela, M. M. S.; Sgarbieri, Valdemiro Carlos

doi:10.1016/j.jped.2013.02.007

Cited by 18 publications

(12 citation statements)

References 34 publications

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“…In contrast to these and our data showing pro-inflammatory actions of TGF-β with inhibitory effects on mucociliary clearance and CFTR function in normal or CF bronchial epithelia 12 , 37 , 38 , several other reports demonstrate TGF-β-mediated anti-inflammatory signaling including decreased Smad 3 levels in CF airway cells 39 – 42 . These discrepancies could be explained by various facts including: 1) dose-dependent effects of TGF-β, 2) differences in cell types (nasal epithelial versus bronchial epithelial cells, cell lines versus primary cultures), primary culture methods (submerged versus air-liquid interface), or 3) disease entity (asthma versus CF).…”

Section: Discussioncontrasting

confidence: 99%

Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia

Krick

Baumlin

Aller

et al. 2017

Sci Rep

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Chronic inflammation is a hallmark of cystic fibrosis (CF) and associated with increased production of transforming growth factor (TGF) β and interleukin (IL)-8. α-klotho (KL), a transmembrane or soluble protein, functions as a co-receptor for Fibroblast Growth Factor (FGF) 23, a known pro-inflammatory, prognostic marker in chronic kidney disease. KL is downregulated in airways from COPD patients. We hypothesized that both KL and FGF23 signaling modulate TGF β-induced IL-8 secretion in CF bronchial epithelia. Thus, FGF23 and soluble KL levels were measured in plasma from 48 CF patients and in primary CF bronchial epithelial cells (CF-HBEC). CF patients showed increased FGF23 plasma levels, but KL levels were not different. In CF-HBEC, TGF-β increased KL secretion and upregulated FGF receptor (FGFR) 1. Despite increases in KL, TGF-β also increased IL-8 secretion via activation of FGFR1 and Smad 3 signaling. However, KL excess via overexpression or supplementation decreased IL-8 secretion by inhibiting Smad 3 phosphorylation. Here, we identify a novel signaling pathway contributing to IL-8 secretion in the CF bronchial epithelium with KL functioning as an endocrine and local anti-inflammatory mediator that antagonizes pro-inflammatory actions of FGF23 and TGF-β.

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Section: Discussioncontrasting

confidence: 99%

Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia

Krick

Baumlin

Aller

et al. 2017

Sci Rep

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“…Unlike the changes in the other two subsets, the increase in FOXP3+ cells was only marginally significant. Indeed, previous reports have suggested reduced levels of Tregs in children with CF [ 18 , 19 ]. Our pediatric group showed no significant changes in any subset we measured, but they were also mostly without chronic infections or antimicrobial treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Because CFTR is primarily a chloride ion channel that indirectly modulates Na + and Ca ++ flux across the membrane, and has been reported to be expressed on lymphocytes [ 10 , 17 ], we hypothesized that altered ion transport resulting from defective CFTR alters T cell responses to antigenic stimulation, and that this alteration may manifest as systemic changes in the relative proportions of different CD4 + T cell subsets. In support of this, varying alterations in the proportions of FOXP3 + Treg [ 18 ], Th17 [ 19 ], mucosal-associated invariant T (MAIT) [ 20 ] cells and changes in the relative production of a number of cytokines in peripheral blood of people with CF have been reported, but it is unclear to what extent this is related to the underlying CFTR defect or whether it is related to infection.…”

Section: Introductionmentioning

confidence: 99%

High Peripheral Blood Th17 Percent Associated with Poor Lung Function in Cystic Fibrosis

et al. 2015

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People with cystic fibrosis (CF) have been reported to make lung T cell responses that are biased towards T helper (Th) 2 or Th17. We hypothesized that CF-related T cell regulatory defects could be detected by analyzing CD4+ lymphocyte subsets in peripheral blood. Peripheral blood mononuclear cells from 42 CF patients (6 months–53 years old) and 78 healthy controls (2–61 years old) were analyzed for Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17+), Treg (FOXP3+), IL-10+ and TGF-β+ CD4+ cells. We observed higher proportions of Treg, IL-10+ and TGF-β+ CD4+ cells in CF adults (≥ 18 years old), but not children/adolescents, compared with controls. Within the CF group, high TGF-β+% was associated with chronic Pseudomonas aeruginosa lung infection (p < 0.006). We observed no significant differences between control and CF groups in the proportions of Th1, Th2 or Th17 cells, and no association within the CF group of any subset with sex, CFTR genotype, or clinical exacerbation. However, high Th17% was strongly associated with poor lung function (FEV1 % predicted) (p = 0.0008), and this association was strongest when both lung function testing and blood sampling were performed within one week. Our results are consistent with reports of CF as a Th17 disease and suggest that peripheral blood Th17 levels may be a surrogate marker of lung function in CF.

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“…There was however, a report of elevated serum IgA and IgM with respect to normal individuals. Bernardi, Ribeiro ( Bernardi et al, 2013 ) reported a significantly higher IgA and IgM level in CF patients. This may be because these were paediatric patients with differing immune response to adults that were recruited in this study.…”

Section: Discussionmentioning

confidence: 96%

The first report on immunoglobulins A, E, G and M levels in cystic fibrosis patients in Saudi Arabia

Alothaid

Banjar

Kebir

et al. 2020

Saudi Journal of Biological Sciences

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Background Previous reports have shown that pulmonary and systemic hypergamma-globulinemia in CF patients is a reflection of chronic pulmonary infection. Infection with Pseudomonas aeruginosa is known to have major prognostic significance in patients CF. This study aims to identify the incidence of immunoglobulins (especially: IgG, and IgE) in a cohort of CF patients. Methods A total of 297 patients recruited all over the country’s region for this study were a as part of the CF registry data from 1st January 1984 to 1st June 2016. All patients had their immunoglobulin levels measured by enzyme link immunosorbent assay (ELISA) in 3 stages, at presentation and two follow-ups. Results Of the 297 patients recruited, 139 (46.8%) were males while 158 (53.2%) were females. IgA and IgM levels were found not to have risen above the previously reported levels in healthy individuals in all stages. On the contrary, IgE level increased from 209.51 ± 32.30 KU/L to 303.58 ± 37.11 KU/L from baseline to stage 3 while IgG level rose from 12.26 ± 0.43 mg/mL to 17.17 ± 1.68 mg/mL for baseline and stage 3 respectively all above previously reported levels in healthy individuals. Conclusion This study establishes a potential for the use of IgE and IgG in disease diagnosis as well as the prognostic implications. However, further study is needed to identify the role of infection or medications in relation to the rise of both IgE and IgG with advancement of age and progression of disease severity which may inherently confound the observed results.

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The Impact of Cystic Fibrosis on the Immunologic Profile of Pediatric Patients

Abstract: Although CF patients appeared clinically stable, the results of their peripheral blood examinations demonstrated an impact on the immune system.

Cited by 18 publications

References 34 publications

Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia

Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia

High Peripheral Blood Th17 Percent Associated with Poor Lung Function in Cystic Fibrosis

The first report on immunoglobulins A, E, G and M levels in cystic fibrosis patients in Saudi Arabia

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