Serum Toll-Like Receptor 2 Concentration in Pediatric Atopic Dermatitis: A Case-Control Study
DOI:
https://doi.org/10.35516/jmj.v60i2.3311Keywords:
Atopic Eczema, Atopic dermatitis, Toll-like receptorsAbstract
Background and Aims: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease. There is increased evidence that Toll-like receptors 2 (TLR2), which are a part of innate immunity, play a role in the pathophysiological changes in AD. The study aims to estimate the serum TLR2 concentration among children with AD compared to healthy controls, and to explore the relationship between serum TLR2 concentration and AD severity and total Immunoglobin E (IgE) level.
Patients and Methods: This case-control study enrolled 156 participants, with 76 atopic dermatitis (AD) cases and 80 controls. It was conducted at the outpatient clinics of Al-Fayhaa Teaching Hospital between December 2020 and March 2021. The study involved interviewing the parents of the participants, detailed clinical examination with assessment of disease severity, and laboratory tests including total IgE and serum TLR2 concentration.
Results: Serum TLR-2 concentrations were lower in AD cases (median= 761.9 pg/ml) than in controls (median=1528.5 pg/ml; P=0.00002). Significantly higher TLR2 levels were seen in patients with elevated IgE (P=0.013) and severe form of AD (P=0.005).
Conclusions: Although lower TLR2 concentrations could indicate their role in AD pathogenesis, higher TLR-2 levels were seen in more severe cases or patients with elevated IgE. This suggests a complex mechanism of TLR2 in the immune dysregulation that occurs in AD. This might refer to the involvement of TLR2 in both the onset and exacerbation of AD, particularly in severe forms.
References
1. M. Ardern‐Jones CF, J. Reynolds, C. Holden. Atopic Eczema. In: Eady RAJ, Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 9 ed. Oxford: Blackwell Science Ltd Oxford; 2016.
2. Paller A, Jaworski JC, Simpson EL, Boguniewicz M, Russell JJ, Block JK, et al. Major Comorbidities of Atopic Dermatitis: Beyond Allergic Disorders. Am J Clin Dermatol. 2018;19(6):821-38.10.1007/s40257-018-0383-4
3. David Boothe W, Tarbox JA, Tarbox MB. Atopic Dermatitis: Pathophysiology. Adv Exp Med Biol. 2017;1027:21-37.10.1007/978-3-319-64804-0_3
4. Kuo IH, Carpenter-Mendini A, Yoshida T, McGirt LY, Ivanov AI, Barnes KC, et al. Activation of epidermal toll-like receptor 2 enhances tight junction function: implications for atopic dermatitis and skin barrier repair. J Invest Dermatol. 2013;133(4):988-98.
DOI: 10.1038/jid.2012.437
5. Lesiak A, Smolewski P, Sobolewska-Sztychny D, Sysa-Jedrzejowska A, Narbutt J. The role of T-regulatory cells and Toll-like receptors 2 and 4 in atopic dermatitis. Scand J Immunol. 2012;76(4):405-10.
6. DOI: 10.1111/j.1365-3083.2012.02739.x
7. Sun L, Liu W, Zhang LJ. The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis. J Immunol Res. 2019;2019:1824624.
DOI: 10.1155/2019/1824624
8. Akan A, Dibek-Misirlioglu E, Civelek E, Vezir E, Kocabas CN. Diagnosis of atopic dermatitis in children: comparison of the Hanifin-Rajka and the United Kingdom Working Party criteria. Allergol Immunopathol (Madr). 2020;48(2):175-81.
DOI: 10.1016/j.aller.2019.07.008
9. Body mass index for age, World Health Organization 2021 [cited 2021 June,24]. Available from:
https://www.who.int/toolkits/child-growth-standards/standards/body-mass-index-for-age-bmi-for-age.
10. Oranje AP, Glazenburg EJ, Wolkerstorfer A, de Waard-van der Spek FB. Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score. Br J Dermatol. 2007;157(4):645-8.
DOI: 10.1111/j.1365-2133.2007.08112.x
11. Al-Rubaye AA-Y, A. Epidemiology and risk factors of atopic dermatitis among children in Basrah, Iraq. International Journal of Public Health Science (IJPHS). 2023;12(2):469-74.
DOI: http://doi.org/10.11591/ijphs.v12i2.22505.
12. Paller AS MA. Atopic Eczema. In: Michael R. Ardern‐Jones CF, Nick J. Reynolds, Colin A. Holden, editor. Hurwitz's Clinical Pediatric Dermatology. 5th ed. London: Elsevier; 2016.
13. Zhang Y, Wang HC, Feng C, Yan M. Analysis of the Association of Polymorphisms rs5743708 in TLR2 and rs4986790 in TLR4 with Atopic Dermatitis Risk. Immunol Invest. 2019;48(2):169-80.
DOI: 10.1080/08820139.2018.1508228
14. Panzer R, Blobel C, Folster-Holst R, Proksch E. TLR2 and TLR4 expression in atopic dermatitis, contact dermatitis and psoriasis. Exp Dermatol. 2014;23(5):364-6.
DOI: 10.1111/exd.12383
15. Tsybikov NN, Petrisheva I, Fefelova EV, Kuznik BI, Magen E. Expression of TLR2 and TLR4 on peripheral blood monocytes during exacerbation of atopic dermatitis. Allergy Asthma Proc. 2015;36(6):e140-5.
DOI: 10.2500/aap.2015.36.3901
16. Niebuhr M, Lutat C, Sigel S, Werfel T. Impaired TLR-2 expression and TLR-2-mediated cytokine secretion in macrophages from patients with atopic dermatitis. Allergy. 2009;64(11):1580-7.DOI: 10.1111/j.1398-9995.2009.02050.x
17. Hasannejad H, Takahashi R, Kimishima M, Hayakawa K, Shiohara T. Selective impairment of Toll-like receptor 2-mediated proinflammatory cytokine production by monocytes from patients with atopic dermatitis. J Allergy Clin Immunol. 2007;120(1):69-75. DOI: 10.1016/j.jaci.2007.04.010
18. Yu Y, Zhang Y, Zhang J, Dou X, Yang H, Shao Y, et al. Impaired Toll-like receptor 2-mediated Th1 and Th17/22 cytokines secretion in human peripheral blood mononuclear cells from patients with atopic dermatitis. J Transl Med. 2015;13:384. DOI: 10.1186/s12967-015-0744-1
19. Terhorst D, Kalali BN, Weidinger S, Illig T, Novak N, Ring J, et al. Monocyte-derived dendritic cells from highly atopic individuals are not impaired in their pro-inflammatory response to toll-like receptor ligands. Clin Exp Allergy. 2007;37(3):381-90.DOI: 10.1111/j.1365-2222.2006.02639.x
20. Vaneckova J, Bukač J. The severity of atopic dermatitis and the relation to the level of total IgE, onset of atopic dermatitis and family history about atopy. Food and Agricultural Immunology. 2016;27(5):734-41. DOI: 10.1046/j.0905-6157.2003.00106.x
21. Hari A, Flach TL, Shi Y, Mydlarski PR. Toll-like receptors: role in dermatological disease. Mediators Inflamm. 2010;2010:437246. DOI: 10.1155/2010/437246
22. Salpietro C, Rigoli L, Miraglia Del Giudice M, Cuppari C, Di Bella C, Salpietro A, et al. TLR2 and TLR4 gene polymorphisms and atopic dermatitis in Italian children: a multicenter study. International journal of immunopathology and pharmacology. 2011;24(4 Suppl):33-40. DOI: 10.1177/03946320110240S408
