T Cell Immunity Profile in Pediatric Obesity and Asthma
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.
[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.
[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.
@article{"International Journal of Medical, Medicine and Health Sciences:69726", author = "Mustafa M. Donma and Erkut Karasu and Burcu Ozdilek and Burhan Turgut and Birol Topcu and Burcin Nalbantoglu and Orkide Donma", title = "T Cell Immunity Profile in Pediatric Obesity and Asthma", 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, flow cytometry, pediatric obesity, T cells.", volume = "9", number = "5", pages = "365-4", }
