Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 30458
T Cell Immunity Profile in Pediatric Obesity and Asthma

Authors: Orkide Donma, Burcin Nalbantoglu, Birol Topcu, Mustafa M. Donma, Erkut Karasu, Burcu Ozdilek, Burhan Turgut

Abstract:

The mechanisms underlying the association between obesity and asthma may be related to a decreased immunological tolerance induced by a defective function of regulatory T cells (Tregs). The aim of this study is to establish the potential link between these diseases and CD4+, CD25+ FoxP3+ Tregs as well as T helper cells (Ths) in children. This is a prospective case control study. Obese (n:40), asthmatic (n:40), asthmatic obese (n:40) and healthy children (n:40), who don't have any acute or chronic diseases, were included in this study. Obese children were evaluated according to WHO criteria. Asthmatic patients were chosen based on GINA criteria. Parents were asked to fill up the questionnaire. Informed consent forms were taken. Blood samples were marked with CD4+, CD25+ and FoxP3+ in order to determine Tregs and Ths by flow cytometric method. Statistical analyses were performed. p≤0.05 was chosen as meaningful threshold. Tregs exhibiting anti-inflammatory nature were significantly lower in obese (0,16%; p≤0,001), asthmatic (0,25%; p≤0,01) and asthmatic obese (0,29%; p≤0,05) groups than the control group (0,38%). Ths were counted higher in asthma group than the control (p≤0,01) and obese (p≤0,001) groups. T cell immunity plays important roles in obesity and asthma pathogeneses. Decreased numbers of Tregs found in obese, asthmatic and asthmatic obese children may help to elucidate some questions in pathophysiology of these diseases. For HOMA-IR levels, any significant difference was not noted between control and obese groups, but statistically higher values were found for obese asthmatics. The values obtained in all groups were found to be below the critical cut off points. This finding has made the statistically significant difference observed between Tregs of obese, asthmatic, obese asthmatic and control groups much more valuable. These findings will be useful in diagnosis and treatment of these disorders and future studies are needed. The production and propagation of Tregs may be promising in alternative asthma and obesity treatments.

Keywords: Asthma, pediatric obesity, flow cytometry, T cells

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1100633

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 1868

References:


[1] D. R. Stukus, “Obesity and asthma: The chicken or the egg?,” J. Allergy Clin. Immunol., to be published.
[2] C. Papoutsakis, K. N. Priftis, M. Drakouli, S. Prifti, E. Konstantaki, M. Chondronikola, G. Antonogeorgos and V. Matziou, “Childhood overweight/obesity and asthma: is there a link? A systematic review of recent epidemiologic evidence,” J. Acad. Nutr. Diet., vol. 113, no. 1, pp. 77-105, Jan. 2013.
[3] M. Sasaki, K. Yoshida, Y. Adachi, M. Furukawa, T. Itazawa, H. Odajima, H. Saito and A. Akasawa, “Factors associated with asthma control in children:findings from a national Web-based survey,” Pediatr. Allergy Immunol., vol. 25, no. 8, pp. 804–809, Dec. 2014.
[4] J. E. Lang, M. J. Hossain and J. J. Lima, “Overweight children report qualitatively distinct asthma symptoms: Analysis of validated symptom measures,” J. Allergy Clin. Immunol., to be published.
[5] G. Weinmayr, F. Forastiere, G. Büchele, A. Jaensch, D. P. Strachan and G. Nagel, “Overweight/obesity and respiratory and allergic disease in children: international study of asthma and allergies in childhood (ISAAC) phase two,” PLoS ONE, vol.9 no. 12, pp. e113996, Dec. 2014.
[6] L. Pacifico, L. Di Renzo, C. Anania, J. F. Osborn, F. Ippoliti, E. Schiavo and C. Chies, “Increased T-helper interferon-γ-secreting cells in obese children,” Eur. J. Endocrinol., vol. 154, no. 5, pp. 691–697, May. 2006.
[7] L. Qi, “Tipping the Balance in Metabolic Regulation: Regulating Regulatory T Cells by Costimulation,” Diabetes, vol. 63 no. 4, pp. 1179–1181, Apr. 2014.
[8] S. Winer, Y. Chan, G. Paltser, D. Truong, H. Tsui, J. Bahrami, R. Dorfman, Y. Wang, J. Zielenski, F. Mastronardi, Y. Maezawa, D.J. Drucker, E. Engleman, D Winer and H. M. Dosch, “Normalization of obesity-associated insulin resistance through immunotherapy,” Nat. Med., vol. 15, no. 8, pp. 921–929, Aug. 2009.
[9] M. Feuerer, L. Herrero, D. Cipolletta, A. Naaz, J. Wong, A. Nayer, J. Lee, A. B. Goldfine, C. Benoist, S. Shoelson and D. Mathis, “Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters,” Nat. Med., vol.15, no. 8, pp. 930–939, Aug. 2009.
[10] M. M. Tiemessen, A. L. Jagger, H. G. Evans, M. J. van Herwijnen, S. John and L. S. Taams, “CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages,” Proc. Natl. Acad. Sci. USA, vol. 104, no. 49, pp.19446–19451, Dec. 2007.
[11] S. Tateya, F. Kim and Y. Tamori, “Recent advances in obesity-induced inflammation and insulin resistance,” Front. Endocrinol., vol. 4, no. A93, pp.1-14, Aug. 2013.
[12] Child growth standards. BMI-for-age (Birth to 5 years) Available from: http://www.who.int/childgrowth/standards/bmi_for_age/en/
[13] Growth reference 5-19 years. BMI-for-age (5-19 years) Available from: http://www.who.int/growthref/who2007_bmi_for_age/en/
[14] D. R. Matthews, J. P. Hosker, A. S. Rudenski, B. A. Naylor, D. F. Treacher and R. C. Turner, “Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man,” Diabetologia, vol. 28, no. 7, pp. 412–419, Jul. 1985.
[15] P. Gunczler and R. Lanes, “Relationship between different fasting-based insulin sensitivity indices in obese children and adolescents,” J. Pediatr. Endocrinol. Metab., vol. 19, no. 3, pp. 259-265, Mar. 2006.
[16] I. R. Madeira, C. N. Carvalho, F. M. Gazolla, H. J. de Matos, M. A. Borges and M. A. Bordallo, “Cut-off point for homeostatic model assesment for insulin resistance (HOMA-IR) index established from receiver operating characteristic (ROC) curve in the detection of metabolic syndrome in overweight pre-pubertal children,” Arq. Bras. Endocrinol. Metabol., vol. 52, no. 9, pp.1466-1473, Dec. 2008.
[17] S. Shalitin and M. Phillip, “Frequency of cardiovascular risk factors in obese children and adolescents referred to a tertiary care center in Israel,” Horm. Res., vol. 69, no. 3, pp. 152-159, 2008.
[18] M. Hamaguchi and S. Sakaguchi, “Regulatory T cells expressing PPAR- γ control inflammation in obesity,” Cell. Metab., vol. 16, no. 1, pp. 4-6, July 2012.
[19] J. M. Han, S. J. Patterson, M. Speck, J. A. Ehses and M. K. Levings, “Insulin inhibits IL-10-mediated regulatory T cell function: Implications for obesity,” J. Immunol., vol. 192, no. 2, pp. 623-629, Jan. 2014.
[20] W. Łuczynski, N. Wawrusiewicz-Kurylonek, E. Iłendo, A. Bossowski, B. Głowińska-Olszewska, A. Kretowski and A. Stasiak-Barmuta, “Generation of functional T-regulatory cells in children with metabolic syndrome,” Arch. Immunol. Ther. Exp., vol. 60, no. 6, pp. 487–495, Dec. 2012.
[21] N. M. Wagner, G. Brandhorst, F. Czepluch, M. Lankeit, C. Eberle, S. Herzberg, V. Faustin, J Riggert, M. Oellerich, G. Hasenfuss, S. Konstantinides and K. Schafer, “Circulating regulatory T cells are reduced in obesity and may identify subjects at increased metabolic and cardiovascular risk,” Obesity (Silver Spring), vol. 21, no. 3, pp. 461-468, 2013.
[22] B. C. Melnik, “The potential mechanistic link between allergy and obesity development and infant formula feeding,” Allergy Asthma Clin. Immunol.,vol. 10, no. 1, pp. 37, July 2014.
[23] T. Hampton, “Studies probe links between childhood asthma and obesity,” JAMA, vol. 311, no. 17, pp. 718-719, May 2014.
[24] M. E. Jensen, L. G. Wood, P. G. Gibson, “Obesity and childhood asthma - mechanisms and manifestations,” Curr. Opin. Allergy Clin. Immunol. vol. 12, no. 2, pp. 186-192, Apr. 2012.
[25] K. Eller, A. Kirsch, A. M. Wolf, S. Sopper, A. Tagwerker, U. Stanzl, D. Wolf, W. Patsch, A. R. Rosenkratz, P. Eller, “Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy,” Diabetes, vol. 60, pp.2954-2962, 2011.
[26] H. L. Tan, D. Gozal, A. Samiel, R. Bhattacharjee, Y. Wang, H. M. Ramirez, H. P. Bandla, R. Kulkarni, L. Kheirandish-Gozal, “Tregulatory lymphocytes and endothelial function in pediatric obstructive sleep apnea,” PlosONE vol. 8, no. 7, pp. e69710, July 2013.