Exploration of early-life candidate biomarkers for childhood asthma using antibody arrays
Haili Xu
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Pharmacology, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorTimothy Radabaugh
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorZhenqiang Lu
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Epidemiology and Biostatistics, College of Public Health, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorMichael Galligan
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorDean Billheimer
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Epidemiology and Biostatistics, College of Public Health, The University of Arizona, Tucson, AZ, USA
Bio5 Institute, The University of Arizona, Tucson, AZ, USA
Statistics Consulting Laboratory, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorDonata Vercelli
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Bio5 Institute, The University of Arizona, Tucson, AZ, USA
Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ, USA
Arizona Respiratory Center, The University of Arizona, Tucson, AZ, USA
Arizona Center for the Biology of Complex Disease, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorAnne L. Wright
Arizona Respiratory Center, The University of Arizona, Tucson, AZ, USA
Department of Pediatrics, College of Medicine, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorTerrence J. Monks
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
Bio5 Institute, The University of Arizona, Tucson, AZ, USA
Arizona Center for the Biology of Complex Disease, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorMarilyn Halonen
Department of Pharmacology, The University of Arizona, Tucson, AZ, USA
Bio5 Institute, The University of Arizona, Tucson, AZ, USA
Arizona Respiratory Center, The University of Arizona, Tucson, AZ, USA
Arizona Center for the Biology of Complex Disease, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorCorresponding Author
Serrine S. Lau
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
Bio5 Institute, The University of Arizona, Tucson, AZ, USA
Arizona Center for the Biology of Complex Disease, The University of Arizona, Tucson, AZ, USA
Correspondence
Serrine S. Lau, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, USA
Tel.: +(313) 577-1574
Fax: +(313) 577-0457
E-mail: [email protected]
Search for more papers by this authorHaili Xu
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Pharmacology, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorTimothy Radabaugh
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorZhenqiang Lu
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Epidemiology and Biostatistics, College of Public Health, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorMichael Galligan
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorDean Billheimer
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Epidemiology and Biostatistics, College of Public Health, The University of Arizona, Tucson, AZ, USA
Bio5 Institute, The University of Arizona, Tucson, AZ, USA
Statistics Consulting Laboratory, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorDonata Vercelli
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Bio5 Institute, The University of Arizona, Tucson, AZ, USA
Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ, USA
Arizona Respiratory Center, The University of Arizona, Tucson, AZ, USA
Arizona Center for the Biology of Complex Disease, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorAnne L. Wright
Arizona Respiratory Center, The University of Arizona, Tucson, AZ, USA
Department of Pediatrics, College of Medicine, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorTerrence J. Monks
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
Bio5 Institute, The University of Arizona, Tucson, AZ, USA
Arizona Center for the Biology of Complex Disease, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorMarilyn Halonen
Department of Pharmacology, The University of Arizona, Tucson, AZ, USA
Bio5 Institute, The University of Arizona, Tucson, AZ, USA
Arizona Respiratory Center, The University of Arizona, Tucson, AZ, USA
Arizona Center for the Biology of Complex Disease, The University of Arizona, Tucson, AZ, USA
Search for more papers by this authorCorresponding Author
Serrine S. Lau
Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, AZ, USA
Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, USA
Bio5 Institute, The University of Arizona, Tucson, AZ, USA
Arizona Center for the Biology of Complex Disease, The University of Arizona, Tucson, AZ, USA
Correspondence
Serrine S. Lau, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, USA
Tel.: +(313) 577-1574
Fax: +(313) 577-0457
E-mail: [email protected]
Search for more papers by this authorAbstract
Background
Proteomic approaches identifying biomarkers have been applied to asthma to only a very limited extent.
Methods
With an antibody array (RayBiotech, Norcross, GA, USA), the relative intensity and rank differences of 444 proteins were compared in 24 plasma samples obtained at age 3, 11 from children with and 12 without asthma diagnoses at ages 5 and 9. Protein candidates identified by antibody array were quantitated by ELISA in an enlarged sample. Proteins found to differentiate children with and without asthma were also examined for association with known Year 1 asthma risk factors, eczema, and wheeze.
Results
In the antibody array, four proteins had rank differences between asthma and non-asthma groups (FDR <0.1). By ELISA, mean log (±s.e.m.) erythropoietin (EPO) level (IU/l) was lower (0.750 ± 0.048 vs. 0.898 ± 0.035; p = 0.006) and mean (±s.e.m.) soluble GP130 (sGP130) level (ng/ml) was higher in the asthma vs. the non-asthma group (302 ± 13 vs. 270 ± 8; p = 0.041). The other 2 array proteins (galactin-3 and eotaxin-3) did not differ by ELISA by asthma. EPO related to the asthma risk factor, first year eczema, whereas sGP130 related to first year wheeze.
Conclusions
Through two independent assessments, age 3 plasma levels of EPO and sGP130 were found related to childhood asthma.
Supporting Information
| Filename | Description |
|---|---|
| pai12613-sup-0001-TableS1.xlsxMS Excel, 16.6 KB | Table S1. List of 444 proteins assessed in the antibody array. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Elias J, Lee CG, Zheng T, Ma B, Homer RJ, Zhu Z. New insights into the pathogenesis of asthma. J Clin Invest 2003: 111: 291–7.
- 2Vercelli D. Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol 2008: 8: 169–82.
- 3Verrills N, Irwin JA, He XY, et al. Identification of novel diagnostic biomarkers for asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2011: 183: 1633–43.
- 4Reubsaet LL, Meerding J, de Jager W, et al. Plasma chemokines in early wheezers predict the development of allergic asthma. Am J Respir Crit Care Med 2013: 188: 1039–40.
- 5Huang R, Jiang W, Yang J, et al. A biotin label-based antibody array for high-content profiling of protein expression. Cancer Genomics Proteomics 2010: 7: 129–41.
- 6Oddy W, Halonen M, Martinez FD, et al. TGF-beta in human milk is associated with wheeze in infancy. J Allergy Clin Immunol 2003: 112: 723–8.
- 7Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc (Series B) 1995: 57: 289–300.
10.1111/j.2517-6161.1995.tb02031.x Google Scholar
- 8Rothers J, Halonen M, Stern DA, et al. Adaptive cytokine production in early life differentially predicts total IgE levels and asthma through age 5 years. J Allergy Clin Immunol 2011: 128: 397–402.
- 9Halonen M, Lohman IC, Stern DA, Ellis WL, Rothers J, Wright AL. Perinatal tumor necrosis factor-α production, influenced by maternal pregnancy weight gain, predicts childhood asthma. Am J Respir Crit Care Med 2013: 188: 35–41.
- 10States DJ, Omenn GS, Blackwell TW, et al. Challenges in deriving high-confidence protein identifications from data gathered by a HUPO plasma proteome collaborative study. Nat Biotechnol 2006: 24: 333–8.
- 11Agnello D, Bigini P, Villa P, et al. Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis. Brain Res 2002: 952: 128–34.
- 12Li Y, Takemura G, Okada H, et al. Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure. Cardiovasc Res 2006: 71: 684–94.
- 13Nairz M, Schroll A, Moschen AR, et al. Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-κB-inducible immune pathways. Immunity 2011: 34: 61–74.
- 14Sirén A, Fratelli M, Brines M, et al. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci U S A. 2001: 98: 4044–9.
- 15Uddin S, Kottegoda S, Stigger D, Platanias LC, Wickrema A. Activation of the Akt/FKHRL1 pathway mediates the antiapoptotic effects of erythropoietin in primary human erythroid progenitors. Biochem Biophys Res Commun 2000: 275: 16–9.
- 16Bany-Mohammed F, Slivka S, Hallman M. Recombinant human erythropoietin: possible role as an antioxidant in premature rabbits. Pediatr Res 1996: 40: 381–7.
- 17Noyan T, Onem O, Ramazan Sekeroğlu M, et al. Effects of erythropoietin and pentoxifylline on the oxidant and antioxidant systems in the experimental short bowel syndrome. Cell Biochem Funct 2003: 21: 49–54.
- 18Budarf M, Huebner K, Emanuel B, et al. Assignment of the erythropoietin receptor (EPOR) gene to mouse chromosome 9 and human chromosome 19. Genomics 1990: 8: 575–8.
- 19Jubinsky P, Krijanovski OI, Nathan DG, Tavernier J, Sieff CA. The beta chain of the interleukin-3 receptor functionally associates with the erythropoietin receptor. Blood 1997: 90: 1867–73.
- 20Watowich S, Hilton DJ, Lodish HF. Activation and inhibition of erythropoietin receptor function: role of receptor dimerization. Mol Cell Biol 1994: 14: 3535–49.
- 21Brines M, Grasso G, Fiordaliso F, et al. Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci U S A 2004: 101: 14907–12.
- 22Sala E, Balaguer C, Villena C, et al. Low erythropoietin plasma levels during exacerbations of COPD. Respiration 2010: 80: 190–7.
- 23Tyagi M, Goyal S, Sathyakumar K, Subbana PK. Influence of erythrocyte function-enhancing drugs on the bronchoprotective actions of chemokine receptor blockers in mice. Med Sci Monit 2006: 12: BR279–82.
- 24Karaman M, Firinci F, Kiray M, et al. Beneficial effects of erythropoietin on airway histology in a murine model of chronic asthma. Allergol Immunopathol (Madr) 2012: 40: 75–80.
- 25Simon D, Denniston AK, Tomlins PJ, et al. Soluble gp130, an antagonist of IL-6 transsignaling, is elevated in uveitis aqueous humor. Invest Ophthalmol Vis Sci 2008: 49: 3988–91.
- 26Jostock T, Müllberg J, Ozbek S, et al. Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem 2001: 268: 160–7.
- 27Doganci A, Eigenbrod T, Krug N, et al. The IL-6R alpha chain controls lung CD4 + CD25 + Treg development and function during allergic airway inflammation in vivo. J Clin Invest 2005: 115: 313–25.
- 28Min J, Jang AS, Park SM, et al. Comparison of plasma eotaxin family level in aspirin-induced and aspirin-tolerant asthma patients. Chest 2005: 128: 3127–32.
- 29Berkman N, Ohnona S, Chung FK, Breuer R. Eotaxin-3 but not Eotaxin gene expression is upregulated in asthmatics 24 hours after allergen challenge. Am J Respir Cell Mol Biol 2001: 24: 682–7.
10.1165/ajrcmb.24.6.4301 Google Scholar
- 30Robertson MW, Albrandt K, Keller D, Liu FT. Human IgE-binding protein: a soluble lectin exhibiting a highly conserved interspecies sequence and differential recognition of IgE glycoforms. Biochemistry 1990: 29: 8093–100.
Citing Literature
