Advanced Search
Share
January - February 2013 The Impact of Cystic Fibrosis on the Immunologic Profile of Pediatric Patients
Journal Information
Previous article | Next article
Vol. 89. Issue 1.
Pages 40-47 (January - February 2013)
Export reference
Share
Share
Print
Download PDF
More article options
Statistics
Vol. 89. Issue 1.
Pages 40-47 (January - February 2013)
Original article
DOI: 10.1016/j.jped.2013.02.007
Open Access
The Impact of Cystic Fibrosis on the Immunologic Profile of Pediatric Patients
Visits
4411
Download PDF
Daniela M. Bernardia,
Corresponding author
dani_miotto@yahoo.com.br

Corresponding author.
, Antonio F. Ribeirob, Tais N. Mazzolac, Maria M.S. Vilelad, Valdemiro C. Sgarbierie
a MSc in Food and Nutrition. Department of Food and Nutrition, School of Food Engineering, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil
b PhD in Child and Adolescent Health. Center for Investigation in Pediatrics, Department of Pediatrics, Medical School, UNICAMP, Campinas, São Paulo, Brazil
c MSc in Child and Adolescent Health. Center for Investigation in Pediatrics, Department of Pediatrics, Medical School, UNICAMP, Campinas, São Paulo, Brazil
d PhD in Biology (Immunology). Center for Investigation in Pediatrics, Department of Pediatrics, Medical School, UNICAMP, Campinas, São Paulo, Brazil
e PhD in Nutrition. Department of Food and Nutrition, School of Food Engineering, UNICAMP, Campinas, São Paulo, Brazil
This item has received
4411 Visits

Under a Creative Commons license
Article information
Abstract
Bibliography
Download PDF
Statistics
Abstract
Objective

To compare the immunologic state of 44 pediatric patients with cystic fibrosis (CF) with a control group consisting of 16 healthy individuals.

 Methods

CF patients aged 3 to 12 years with moderate to good clinical score were selected for the study. Erythrocytic glutathione, production of reactive oxygen species, cytokines (TNF-a, IFN-g, IL-8, IL-6, IL-10) in peripheral blood mononuclear cells cultures under spontaneous and BCG- or PHA-stimulated conditions, serum concentrations of TGF-b2, IgA, IgG, IgM, IgE, and salivary IgA were evaluated.

 Results

The spontaneous production of TNF-a, IL-6, and IL-10, the PHA-stimulated production of IL-6, and the serum TGF-b2, IgA, and IgG were increased in samples from CF patients. Healthy subjects had a higher production of TNF-a in response to BCG.

 Conclusion

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

Keywords:
Cystic fibrosis
Reactive oxygen species
Glutathione
Cytokines
Immunoglobulins
Resumo
Objetivo

Comparar o estado imunológico de 44 pacientes pediátricos com fibrose cística (FC) a um grupo-controle formado por 16 indivíduos saudáveis.

 Métodos

Foram selecionados para o estudo pacientes com FC com idade entre 3 e 12 anos, apresentando um escore clínico moderado e bom. Foram avaliados a glutationa eritrocitária, a produção de espécies reativas de oxigênio, citocinas (TNF-a, IFN-g, IL-8, IL-6, IL-10) em culturas de células mononucleares do sangue periférico em condições espontâneas e estimuladas por BCG ou PHA, a concentração sérica de TGF-b2, IgA, IgG, IgM, IgE e IgA salivar.

 Resultados

A produção espontânea de TNF-a, IL-6 e IL-10, a produção de IL-6 estimula- da por PHA e TGF-b2, IgA e IgG séricas aumentaram em amostras de pacientes com FC. Indivíduos saudáveis tiveram uma produção mais elevada de TNF-a em resposta a BCG.

 Conclusão

Apesar de os pacientes com FC parecerem clinicamente estáveis, os resul- tados de seus exames de sangue periférico mostraram que houve um impacto sobre o sistema imunológico.

Palavras-chave:
Fibrose cística
Espécies reativas de oxigênio
Glutationa
Citocinas
Imunoglobulinas
Full text is only aviable in PDF
References
[1]
B.P. O'Sullivan, S.D. Freedman.
Cystic fibrosis.
Lancet., 373 (2009), pp. 1891-1904
http://dx.doi.org/10.1016/S0140-6736(09)60327-5 | Medline
[2]
J.C. Cheung, P. Kim Chiaw, S. Pasyk, C.E. Bear.
Molecular basis for the ATPase activity of CFTR.
Arch Biochem Biophys., 476 (2008), pp. 95-100
http://dx.doi.org/10.1016/j.abb.2008.03.033 | Medline
[3]
M. Rottner, J.M. Freyssinet, M.C. Martínez.
Mechanisms of the noxious inflammatory cycle in cystic fibrosis.
Respir Res., 10 (2009), pp. 23
http://dx.doi.org/10.1186/1465-9921-10-23 | Medline
[4]
T.S. Cohen, A. Prince.
Cystic fibrosis: a mucosal immunodeficiency syndrome.
Nat Med., 18 (2012), pp. 509-519
http://dx.doi.org/10.1038/nm.2715 | Medline
[5]
E. Beutler.
Red Cell Metabolism.
Churchill Livingstone, (1986),
[6]
A. Emmendörffer, M. Hecht, M.L. Lohmann-Matthes, J. Roesler.
A fast and easy method to determine the production of reactive oxygen intermediates by human and murine phagocytes using dihydrorhodamine 123.
J Immunol Methods., 131 (1990), pp. 269-275
Medline
[7]
M.P. Richardson, M.J. Ayliffe, M. Helbert, E.G. Davies.
A simple flow cytometry assay using dihydrorhodamine for the measurement of the neutrophil respiratory burst in whole blood: comparison with the quantitative nitrobluetetrazolium test.
J Immunol Methods., 219 (1998), pp. 187-193
Medline
[8]
H. Gaines, L. Andersson, G. Biberfeld.
A new method for measuring lymphoproliferation at the single-cell level in whole blood cultures by flow cytometry.
J Immunol Methods., 195 (1996), pp. 63-72
Medline
[9]
E. Boncoeur, V.S. Criq, E. Bonvin, T. Roque, A. Henrion-Caude, D.C. Gruenert, et al.
Oxidative stress induces extracellular signal- regulated kinase 1/2 mitogen-activated protein kinase in cystic fibrosis lung epithelial cells: potential mechanism for excessive IL-8 expression.
Int J Biochem Cell Biol., 40 (2008), pp. 432-446
http://dx.doi.org/10.1016/j.biocel.2007.08.013 | Medline
[10]
S. Mangione, D.D. Patel, B.R. Levin, S.B. Fiel.
Erythrocytic glutathione in cystic fibrosis. A possible marker of pulmonary dysfunction.
Chest., 105 (1994), pp. 1470-1473
Medline
[11]
L.C. Lands, V. Grey, A.A. Smountas, V.G. Kramer, D. McKenna.
Lymphocyte glutathione levels in children with cystic fibrosis.
Chest., 116 (1999), pp. 201-205
Medline
[12]
L. Gao, K.J. Kim, J.R. Yankaskas, H.J. Forman.
Abnormal glutathione transport in cystic fibrosis airway epithelia.
Am J Physiol., 277 (1999), pp. L113-L118
Medline
[13]
D. Norman, J.S. Elborn, S.M. Cordon, R.J. Rayner, M.S. Wiseman, E.J. Hiller, et al.
Plasma tumour necrosis factor alpha in cystic fibrosis.
Thorax., 46 (1991), pp. 91-95
Medline
[14]
K. Balough, M. McCubbin, M. Weinberger, W. Smits, R. Ahrens, R. Fick.
The relationship between infection and inflammation in the early stages of lung disease from cystic fibrosis.
Pediatr Pulmonol., 20 (1995), pp. 63-70
Medline
[15]
T.L. Bonfield, J.R. Panuska, M.W. Konstan, K.A. Hilliard, J.B. Hilliard, H. Ghnaim, et al.
Inflammatory cytokines in cystic fibrosis lungs.
Am J Respir Crit Care Med., 152 (1995), pp. 2111-2118
http://dx.doi.org/10.1164/ajrccm.152.6.8520783 | Medline
[16]
E. Osika, J.M. Cavaillon, K. Chadelat, M. Boule, C. Fitting, G. Tournier, et al.
Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease.
Eur Respir J., 14 (1999), pp. 339-346
Medline
[17]
F. Karpati, F.L. Hjelte, B. Wretlind.
TNF-alpha and IL-8 in consecutive sputum samples from cystic fibrosis patients during antibiotic treatment.
Scand J Infect Dis., 32 (2000), pp. 75-79
Medline
[18]
A.L. Pukhalsky, N.I. Kapranov, E.A. Kalashnikova, G.V. Shmarina, L.A. Shabalova, S.N. Kokarovtseva, et al.
Inflammatory markers in cystic fibrosis patients with lung Pseudomonas aeruginosa infection.
Mediators Inflamm., 8 (1999), pp. 159-167
http://dx.doi.org/10.1080/09629359990496 | Medline
[19]
C. Moser, S. Kjaergaard, T. Pressler, A. Kharazmi, C. Koch, N. Høiby.
The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type.
APMIS., 108 (2000), pp. 329-335
Medline
[20]
C. Wojnarowski, T. Frischer, E. Hofbauer, C. Grabner, W. Mosgoeller, I. Eichler, et al.
Cytokine expression in bronchial biopsies of cystic fibrosis patients with and without acute exacerbation.
Eur Respir J., 14 (1999), pp. 1136-1144
Medline
[21]
T.L. Noah, H.R. Black, P.W. Cheng, R.E. Wood, M.W. Leigh.
Nasal and bronchoalveolar lavage fluid cytokines in early cystic fibrosis.
J Infect Dis., 175 (1997), pp. 638-647
Medline
[22]
L.S. Nixon, B. Yung, S.C. Bell, J.S. Elborn, D.J. Shale.
Circulating immunoreactive interleukin-6 in cystic fibrosis.
Am J Respir Crit Care Med., 157 (1998), pp. 1764-1769
http://dx.doi.org/10.1164/ajrccm.157.6.9704086 | Medline
[23]
D. Nichols, J. Chmiel, M. Berger.
Chronic inflammation in the cystic fibrosis lung: alterations in inter- and intracellular signaling.
Clin Rev Allergy Immunol., 34 (2008), pp. 146-162
http://dx.doi.org/10.1007/s12016-007-8039-9 | Medline
[24]
R.B. Moss, R.C. Bocian, Y.P. Hsu, Y.J. Dong, M. Kemna, T. Wei, et al.
Reduced IL-10 secretion by CD4+ T lymphocytes expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR).
Clin Exp Immunol., 106 (1996), pp. 374-388
Medline
[25]
J.N. Rosensweig, M. Omori, K. Page, C.J. Potter, E.J. Perlman, S.S. Thorgeirsson, et al.
Transforming growth factor-beta1 in plasma and liver of children with liver disease.
Pediatr Res., 44 (1998), pp. 402-409
http://dx.doi.org/10.1203/00006450-199809000-00023 | Medline
[26]
M.A. South, W.J. Warwick, F.A. Wolheim, R.A. Good.
The IgA system. 3. IgA levels in the serum and saliva of pediatric patients-evidence for a local immunological system.
J Pediatr., 71 (1967), pp. 645-653
Medline
[27]
E. Gugler, J.C. Pallavicini, H. Swedlow, I. Zipkin, P.A. Agnese.
Immunological studies of submaxillary saliva from patients with cystic fibrosis and from normal children.
J Pediatr., 73 (1968), pp. 548-559
Medline
[28]
M.E. Hodson, L. Morris, J.C. Batten.
Serum immunoglobulins and immunoglobulin G subclasses in cystic fibrosis related to the clinical state of the patient.
Eur Respir J., 1 (1988), pp. 701-705
Medline
[29]
W.J. Matthews Jr., M. Williams, B. Oliphint, R. Geha, H.R. Colten.
Hypogammaglobulinemia in patients with cystic fibrosis.
N Engl J Med., 302 (1980), pp. 245-249
http://dx.doi.org/10.1056/NEJM198001313020501 | Medline
[30]
W.B. Wheeler, M. Williams, W.J. Matthews Jr., H.R. Colten.
Progression of cystic fibrosis lung disease as a function of serum immunoglobulin G levels: a 5-year longitudinal study.
J Pediatr., 104 (1984), pp. 695-699
Medline
[31]
F. Harrison.
Microbial ecology of the cystic fibrosis lung.
Microbiology., 153 (2007), pp. 917-923
http://dx.doi.org/10.1099/mic.0.2006/004077-0 | Medline
[32]
D.E. Griffith, T. Aksamit, B.A. Brown-Elliott, A. Catanzaro, C. Daley, F. Gordin, et al.
An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases.
Am J Respir Crit Care Med., 175 (2007), pp. 367-416
http://dx.doi.org/10.1164/rccm.200604-571ST | Medline
[33]
T.M. Kremer, R.G. Zwerdling, P.H. Michelson, P. O'Sullivan.
Intensive care management of the patient with cystic fibrosis.
J Intensive Care Med., 23 (2008), pp. 159-177
http://dx.doi.org/10.1177/0885066608315679 | Medline
[34]
J.W. Costerton, P.S. Stewart, E.P. Greenberg.
Bacterial biofilms: a common cause of persistent infections.
Science., 284 (1999), pp. 1318-1322
Medline
[35]
T.H. Ottenhoff.
New pathways of protective and pathological host defense to mycobacteria.
Trends Microbiol., 20 (2012), pp. 419-428
http://dx.doi.org/10.1016/j.tim.2012.06.002 | Medline
[36]
G.B. Pier.
The challenges and promises of new therapies for cystic fibrosis.
J Exp Med., 209 (2012), pp. 1235-1239
http://dx.doi.org/10.1084/jem.20121248 | Medline
☆

Please, cite this article as: Bernardi DM, Ribeiro AF, Mazzola TN, Vilela MM, Sgarbieri VC. The impact of cystic fibrosis on the immunologic profile of pediatric patients. J Pediatr (Rio J). 2013;89:40-47.

Copyright © 2013. Sociedade Brasileira de Pediatria

Subscribe to our newsletter

Publish in
Jornal de Pediatria
ORIGINAL ARTICLES
South Cone Section
Selected articles published in pediatric journals of the South Cone
Read selection
Issue nº 1
Download issue nº 1 of Jornal de Pediatria, 1934
Year
1934
Jornal do Pediatria nº1
Download PDF
Idiomas
Jornal de Pediatria (English Edition)
Article options
Tools
en pt
Taxa de publicaçao Publication fee
Os artigos submetidos a partir de 1º de setembro de 2018, que forem aceitos para publicação no Jornal de Pediatria, estarão sujeitos a uma taxa para que tenham sua publicação garantida. O artigo aceito somente será publicado após a comprovação do pagamento da taxa de publicação. Ao submeterem o manuscrito a este jornal, os autores concordam com esses termos. A submissão dos manuscritos continua gratuita. Para mais informações, contate assessoria@jped.com.br. Articles submitted as of September 1, 2018, which are accepted for publication in the Jornal de Pediatria, will be subject to a fee to have their publication guaranteed. The accepted article will only be published after proof of the publication fee payment. By submitting the manuscript to this journal, the authors agree to these terms. Manuscript submission remains free of charge. For more information, contact assessoria@jped.com.br.
Cookies policy Política de cookies
To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.