CD14 as A Serum Immune Biomarker and Genetic Predisposition Factor for Allergic Rhinitis

Document Type: Original


1 Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Research Centre of Iranian Blood Transfusion Organization, Khorasan Razavi, Mashhad, Iran


Allergic Rhinitis (AR) is a common inflammatory disease of the nasal mucosa. The CD14 is a receptor for lipopolysaccharide and inhaled endotoxin which can stimulate the production of interleukins by antigen presenting cells. Accordingly, CD14 plays an important role in allergic and atopic diseases, which can be one of the etiological factors for allergic diseases. The present study investigated the association between the CD14 gene polymorphism C-159T and AR and aimed to detect the correlation between serum levels of CD14 and AR.
Materials and Methods:
This study was conducted on two groups of participants. The experimental group consisted of 125 patients with AR referring to Ghaem Hospital, Mashhad University of Medical Sciences in Mashhad, Iran, and the control group included 125 healthy subjects from Mashhad National Blood Center, Iran. Serum CD14 levels were measured by enzyme-linked immunosorbent assay. Polymerase chain reaction-restriction fragment length polymorphism was employed to detect C-159T gene polymorphism in the CD14 promoter region.
There was a significant association between CD14 C-159T gene polymorphism and AR (P<0.001). The results of the statistical analysis showed that the TT genotype could significantly increase the risk of AR (P<0.001). Additionally, a significant association was observed between C-159T gene polymorphism and the serum level of CD14 (P<0.001). Regardless of the genotypes, the serum CD14 levels were significantly higher in AR patients than in those of the participants in the controls (P=0.007).
According to the obtained results of this study, CD14 in serum might be a potential marker for the diagnosis of AR, and in genetic levels it might be a predictive factor for the disease.


Main Subjects

1. Scadding GK. Allergic rhinitis: background, symptoms, diagnosis and treatment options. benefits. 2017;10:32.

2. Zare Marzouni H, Akrami R, Shalilian M, Kalani N, Noori Ahmad Abadi M, Kooti W. Investigating the Prevalence, Determining the Effects of Immunologic Sensitization and Clinical Symptoms Related to Allergens Existing in Khuzestan Province. Journal of Fasa University of Medical Sciences. 2016;6(1):96-105.

3. Meltzer EO. Allergic rhinitis: burden of illness, quality of life, comorbidities, and control. Immunology and allergy clinics of North America. 2016; 36(2):235-48.

4. Langdon C, Guilemany JM, Valls M, Alobid I, Bartra J, Dávila I, et al. Allergic rhinitis causes loss of smell in children: The OLFAPEDRIAL study. Pediatric Allergy and Immunology. 2016; 27(8): 867-70.

5. Scadding GK, Scadding GW. Diagnosing Allergic Rhinitis. Immunology and allergy clinics of North America. 2016;36(2):249-60.

6. Yazdani N, Amoli M, Naraghi M, Mersaghian A, Firouzi F, Sayyahpour F, et al. 3 Association Between the Functional Polymorphism C-159T in the CD14 Promoter Gene and Nasal Polyposis: Potential Role in Asthma. Journal of Investigational Allergology and Clinical Immunology. 2012; 22(6): 406.

7. Hamajima Y, Fujieda S, Sunaga H, Yamada T, Moribe K, Watanabe N, et al. Expression of Syk is associated with nasal polyp in patients with allergic rhinitis. Auris Nasus Larynx. 2007;34(1):49-56.

8. Verhasselt V, Buelens C, Willems F, De Groote D, Haeffner-Cavaillon N, Goldman M. Bacterial lipopolysaccharide stimulates the production of cytokines and the expression of costimulatory molecules by human peripheral blood dendritic cells: evidence for a soluble CD14-dependent pathway. The Journal of Immunology. 1997;158(6):2919-25.

9. Zanoni I, Ostuni R, Marek LR, Barresi S, Barbalat R, Barton GM, et al. CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. Cell. 2011;147(4):868-80.

10. Han D SW, Zhang L. Association of the CD14 gene polymorphism C-159T with allergic rhinitis. Am J Rhinol Allergy. 2010;24(1):e1-3.

11. Keskin Ö, Birben E, Saçkesen C, Soyer ÖU, Alyamaç E, Karaaslan Ç, et al. The effect of CD14-c159T genotypes on the cytokine response to endotoxin by peripheral blood mononuclear cells from asthmatic children. Annals of Allergy, Asthma & Immunology. 2006;97(3):321-8.

12. Kurne A, Sayat G, Aydin OF, Turgutoglu N, Terzi M, Sackesen C, et al. Lack of association of the CD14/ C− 159T polymorphism with susceptibility and progression parameters in Turkish multiple sclerosis patients. Journal of neuroimmunology. 2012;250(1):83-6.

13. Leynaert B, Guilloud-Bataille M, Soussan D, Benessiano J, Guénégou A, Pin I, et al. Association between farm exposure and atopy, according to the CD14 C-159T polymorphism. Journal of allergy and clinical immunology. 2006;118(3):658-65.

14. Litonjua AA, Belanger K, Celedón JC, Milton DK, Bracken MB, Kraft P, et al. Polymorphisms in the 5′ region of the CD14 gene are associated with eczema in young children. Journal of allergy and clinical immunology. 2005;115(5):1056-62.

15. Mortazavi H, Khalighi H, Goljanian A, Noormohammadi R, Mojahedi S, Sabour S. Intra-oral low level laser therapy in chronic maxillary sinusitis: A new and effective recommended technique. Journal of clinical and experimental dentistry. 2015;7(5):e557.

16. Mohammadi M, Zahedi MJ, Nikpoor AR, Baneshi MR, Hayatbakhsh MM. Interleukin-17 serum levels and TLR4 polymorphisms in ulcerative colitis. Iranian Journal of Immunology. 2013; 10(2):83.

17. Hata Y, Duh E, Zhang K, Robinson GS, Aiello LP. Transcription factors Sp1 and Sp3 alter vascular endothelial growth factor receptor expression through a novel recognition sequence. Journal of Biological Chemistry. 1998; 273(30): 19294-303.

18. LeVan TD, Bloom JW, Bailey TJ, Karp CL, Halonen M, Martinez FD, et al. A common single nucleotide polymorphism in the CD14 promoter decreases the affinity of Sp protein binding and enhances transcriptional activity. The Journal of Immunology. 2001;167(10):5838-44.

19. Tahara T, Arisawa T, Shibata T, Hirata I, Nakano H. Association of polymorphism of TLR4 and CD14 genes with gastroduodenal diseases in Japan. Inflammopharmacology. 2007;15(3):124-8.

20. Gao PS, Mao XQ, Baldini M, Roberts M, Adra C, Shirakawa T, et al. Serum total IgE levels and CD14 on chromosome 5q31. Clinical genetics. 1999; 56(2):164-5.

21. Bučková D, Holla L, Schüller M, Znojil V, Vacha J. Two CD14 promoter polymorphisms and atopic phenotypes in Czech patients with IgE‐mediated allergy. Allergy. 2003;58(10):1023-6.

22. Baldini M, Carla Lohman I, Halonen M, Erickson RP, Holt PG, Martinez FD. A Polymorphism* in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. American journal of respiratory cell and molecular biology. 1999;20(5):976-83.

23. Choudhry S AP, Nazario S. CD14 tobacco gene-environment interaction modifies asthma severity and immunoglobulin E levels in Latinos with asthma. Am J Respir Crit Care Med. 2005;172:173- 82.

24. Dennig J, Hagen G, Beato M, Suske G. Members of the Sp transcription factor family control transcription from the uteroglobin promoter. Journal of Biological Chemistry. 1995; 270(21):12737-44.

25. Sengler C, Haider A, Sommerfeld C, Lau S, Baldini M, Martinez F, et al. Evaluation of the CD14 C‐159 T polymorphism in the German Multicenter Allergy Study cohort. Clinical & Experimental Allergy. 2003;33(2):166-9.

26. Koppelman GH, Reijmerink NE, Colin Stine O, Howard TD, Whittaker PA, Meyers DA, et al. Association of a promoter polymorphism of the CD14 gene and atopy. American journal of respiratory and critical care medicine. 2001; 163(4): 965-9.

27. Kowal K, Bodzenta-Lukaszyk A, Pampuch A, Szmitkowski M, Zukowski S, Donati MB, et al. Analysis of -675 4 g/5 G SERPINE1 and C-159T CD14 polymorphisms in house dust mite-allergic asthma patients. Journal of investigational allergology & clinical immunology. 2008; 18(4): 284-92.

28. Sharma M, Batra J, Mabalirajan U, Goswami S, Ganguly D, Lahkar B, et al. Suggestive evidence of association of C-159T functional polymorphism of the CD14 gene with atopic asthma in northern and northwestern Indian populations. Immunogenetics. 2004;56(7):544-7.

29. Eder W, Klimecki W, Yu L, Von Mutius E, Riedler J, Braun-Fahrländer C, et al. Opposite effects of CD14/-260 on serum IgE levels in children raised in different environments. Journal of Allergy and Clinical Immunology. 2005; 116(3): 601-7.

30. Simpson A, John SL, Jury F, Niven R, Woodcock A, Ollier WE, et al. Endotoxin exposure, CD14, and allergic disease: an interaction between genes and the environment. American journal of respiratory and critical care medicine. 2006; 174(4):386-92.

31. Williams LK, McPhee RA, Ownby DR, Peterson EL, James M, Zoratti EM, et al. Gene-environment interactions with CD14 C-260T and their relationship to total serum IgE levels in adults. Journal of Allergy and Clinical Immunology. 2006;118(4):851-7.

32. Gern JE, Reardon CL, Hoffjan S, Nicolae D, Li Z, Roberg KA, et al. Effects of dog ownership and genotype on immune development and atopy in infancy. Journal of Allergy and Clinical Immunology. 2004;113(2):307-14.

33. Barber D, De La Torre F, Feo F, Florido F, Guardia P, Moreno C, et al. Understanding patient sensitization profiles in complex pollen areas: a molecular epidemiological study. Allergy. 2008;63(11):1550-8.

34. Pereira C, Valero A, Loureiro C, Davila I, Martinez-Cocera C, Murio C, et al. Iberian study of aeroallergens sensitisation in allergic rhinitis. European annals of allergy and clinical immunology. 2006;38(6):186.

35. Fereidouni M, Hossini RF, Azad FJ, Assarezadegan MA, Varasteh A. Skin prick test reactivity to common aeroallergens among allergic rhinitis patients in Iran. Allergologia et immunopathologia. 2009;37(2):73-9.

36. Akbari H RA. Common allergens for allergic patients in Isfahan: A clinically-based study. Journal of Research In Medical Sciences. 2000; 5(1): 12-8.

37. Sahlander K, Larsson K, Palmberg L. Increased serum levels of soluble ST2 in birch pollen atopics and individuals working in laboratory animal facilities. Journal of occupational and environmental medicine. 2010;52(2):214-8.

38. Tan C-Y, Chen Y-L, Wu LS-H, Liu C-F, Chang W-T, Wang J-Y. Association of CD14 promoter polymorphisms and soluble CD14 levels in mite allergen sensitization of children in Taiwan. Journal of human genetics. 2006;51(1):59-67.

39. Kagan JC, Su T, Horng T, Chow A, Akira S, Medzhitov R. TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β. Nature immunology. 2008;9(4):361-8.

40. Akira S, Takeda K. Toll-like receptor signalling. Nature reviews immunology. 2004; 4(7): 499-511.