Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Author(s): Rui Tang, Xiaohong Lyu, Jinlyu Sun* and Hong Li*

DOI: 10.2174/0118715303285101240118062549

DownloadDownload PDF Flyer Cite As
Genetic Polymorphisms of GP1BA, PEAR1, and PAI-1 may be Associated with Serum sIgE and Blood Eosinophil Levels in Chinese Patients with Allergic Diseases

Page: [1215 - 1223] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: It has been suggested that genetic factors may be substantially linked to allergy disorders.

Objective: This study aims to investigate the relationship between the serum specific Immunoglobulin E (sIgE), blood eosinophil, and the polymorphisms of glycoprotein Ib alpha gene (GP1BA) rs6065, platelet endothelial aggregation receptor 1 gene (PEAR1) rs12041331, and plasminogen activator inhibitor 1 gene (PAI-1) rs1799762.

Methods: From the Peking Union Medical College Hospital, this study enrolled 60 healthy participants and 283 participants with allergic diseases. TaqMan-minor groove binder (MGB) quantitative polymerase chain reaction (qPCR) was used to examine the gene polymorphisms in each group.

Results: The TaqMan-MGB qPCR results were completely consistent with the DNA sequencing results, according to other studies in this medical center (Kappa =1, p <0.001). The GP1BA rs6065, PEAR1 rs12041331, and PAI-1 rs1799762 polymorphisms did not show different distribution between allergy patients and healthy individuals. Concerning allergy patients, the CT (n=33) genotype of GP1BA rs6065 had higher blood eosinophil level than the CC (n=250) genotype (0.59, IQR 0.32-0.72 vs 0.31, IQR 0.15-0.61, *109/L, p =0.005). The serum sIgE of AA (n=46) genotype of PEAR1 rs12041331 was lower (median 3.7, interquartile quartiles (IQR) 0.2-16.8, kU/L) than the GA (n=136) and GG (n=101) genotypes (GA median 16.3, IQR 3.1-46.3, kU/L, p = 0.002; GG median 12.9, IQR 3.0-46.9, kU/L, p =0.003). The GA genotypes of PEAR1 rs12041331were with higher blood eosinophil levels (median 0.42, IQR 0.17-0.74 *109/L) than the AA genotype (median 0.25, IQR 0.15-0.41*109/L, p =0.012). The sIgE of the 5G5G (n=44) genotype of PAI-1 rs1799762 was lower (median 5.0, IQR 0.1-22.8, kU/L) than the 4G5G (n=144) (median 17.3, IQR 3.7-46.0, kU/L, p = 0.012).

Conclusion: The GP1BA rs6065, PEAR1 rs12041331, and PAI-1 rs1799762 polymorphisms may be associated with the genetic susceptibility of serum sIgE or blood eosinophil in Chinese allergic disease patients.

Graphical Abstract

[1]
Simon, D. Recent advances in clinical allergy and immunology 2019. Int. Arch. Allergy Immunol., 2019, 180(4), 291-305.
[http://dx.doi.org/10.1159/000504364] [PMID: 31694018]
[2]
Sroka-Tomaszewska, J.; Trzeciak, M. Molecular mechanisms of atopic dermatitis pathogenesis. Int. J. Mol. Sci., 2021, 22(8), 4130.
[http://dx.doi.org/10.3390/ijms22084130] [PMID: 33923629]
[3]
Bousquet, J.; Anto, J.M.; Bachert, C.; Baiardini, I.; Bosnic-Anticevich, S.; Canonica, W.G.; Melén, E.; Palomares, O.; Scadding, G.K.; Togias, A.; Toppila-Salmi, S. Allergic rhinitis. Nat. Rev. Dis. Primers, 2020, 6(1), 95.
[http://dx.doi.org/10.1038/s41572-020-00227-0] [PMID: 33273461]
[4]
Tiotiu, A.I.; Novakova, S.; Labor, M.; Emelyanov, A.; Mihaicuta, S.; Novakova, P.; Nedeva, D. Progress in occupational asthma. Int. J. Environ. Res. Public Health, 2020, 17(12), 4553.
[http://dx.doi.org/10.3390/ijerph17124553] [PMID: 32599814]
[5]
Zhang, Y.; Lan, F.; Zhang, L. Advances and highlights in allergic rhinitis. Allergy, 2021, 76(11), 3383-3389.
[http://dx.doi.org/10.1111/all.15044] [PMID: 34379805]
[6]
Li, S.; Wu, W.; Wang, G.; Zhang, X.; Guo, Q.; Wang, B.; Cao, S.; Yan, M.; Pan, X.; Xue, T.; Gong, J.; Duan, X. Association between exposure to air pollution and risk of allergic rhinitis: A systematic review and meta-analysis. Environ. Res., 2022, 205, 112472.
[http://dx.doi.org/10.1016/j.envres.2021.112472] [PMID: 34863689]
[7]
Han, X.; Krempski, J.W.; Nadeau, K. Advances and novel developments in mechanisms of allergic inflammation. Allergy, 2020, 75(12), 3100-3111.
[http://dx.doi.org/10.1111/all.14632] [PMID: 33068299]
[8]
Miller, R.L.; Grayson, M.H.; Strothman, K. Advances in asthma: New understandings of asthma’s natural history, risk factors, underlying mechanisms, and clinical management. J. Allergy Clin. Immunol., 2021, 148(6), 1430-1441.
[http://dx.doi.org/10.1016/j.jaci.2021.10.001] [PMID: 34655640]
[9]
Peters, R.L.; Krawiec, M.; Koplin, J.J.; Santos, A.F. Update on food allergy. Pediatr. Allergy Immunol., 2021, 32(4), 647-657.
[http://dx.doi.org/10.1111/pai.13443] [PMID: 33370488]
[10]
Ogulur, I.; Pat, Y.; Ardicli, O.; Barletta, E.; Cevhertas, L.; Fernandez-Santamaria, R.; Huang, M.; Imam, B.M.; Koch, J.; Ma, S.; Maurer, D.J.; Mitamura, Y.; Peng, Y.; Radzikowska, U.; Rinaldi, A.O.; Rodriguez-Coira, J.; Satitsuksanoa, P.; Schneider, S.R.; Wallimann, A.; Zhakparov, D.; Ziadlou, R.; Brüggen, M.C.; van de Veen, W.; Sokolowska, M.; Baerenfaller, K.; Zhang, L.; Akdis, M.; Akdis, C.A. Advances and highlights in biomarkers of allergic diseases. Allergy, 2021, 76(12), 3659-3686.
[http://dx.doi.org/10.1111/all.15089] [PMID: 34519063]
[11]
Sonntag, H.J.; Filippi, S.; Pipis, S.; Custovic, A. Blood biomarkers of sensitization and asthma. Front Pediatr., 2019, 7, 251.
[http://dx.doi.org/10.3389/fped.2019.00251] [PMID: 31275911]
[12]
de Bortoli, N.; Penagini, R.; Savarino, E.; Marchi, S. Eosinophilic esophagitis: Update in diagnosis and management. Position paper by the Italian Society of Gastroenterology and Gastrointestinal Endoscopy (SIGE). Dig. Liver Dis., 2017, 49(3), 254-260.
[http://dx.doi.org/10.1016/j.dld.2016.11.012] [PMID: 27979389]
[13]
Rondón, C.; Canto, G.; Blanca, M. Local allergic rhinitis: A new entity, characterization and further studies. Curr. Opin. Allergy Clin. Immunol., 2010, 10(1), 1-7.
[http://dx.doi.org/10.1097/ACI.0b013e328334f5fb] [PMID: 20010094]
[14]
Li, L.; Liu, R.; Peng, C.; Chen, X.; Li, J. Pharmacogenomics for the efficacy and side effects of antihistamines. Exp. Dermatol., 2022, 31(7), 993-1004.
[http://dx.doi.org/10.1111/exd.14602] [PMID: 35538735]
[15]
Sharma, M.; Leung, D.; Momenilandi, M.; Jones, L.C.W.; Pacillo, L.; James, A.E.; Murrell, J.R.; Delafontaine, S.; Maimaris, J.; Vaseghi-Shanjani, M.; Del Bel, K.L.; Lu, H.Y.; Chua, G.T.; Di Cesare, S.; Fornes, O.; Liu, Z.; Di Matteo, G.; Fu, M.P.; Amodio, D.; Tam, I.Y.S.; Chan, G.S.W.; Sharma, A.A.; Dalmann, J.; van der Lee, R.; Blanchard-Rohner, G.; Lin, S.; Philippot, Q.; Richmond, P.A.; Lee, J.J.; Matthews, A.; Seear, M.; Turvey, A.K.; Philips, R.L.; Brown-Whitehorn, T.F.; Gray, C.J.; Izumi, K.; Treat, J.R.; Wood, K.H.; Lack, J.; Khleborodova, A.; Niemela, J.E.; Yang, X.; Liang, R.; Kui, L.; Wong, C.S.M.; Poon, G.W.K.; Hoischen, A.; van der Made, C.I.; Yang, J.; Chan, K.W.; Rosa Duque, J.S.D.; Lee, P.P.W.; Ho, M.H.K.; Chung, B.H.Y.; Le, H.T.M.; Yang, W.; Rohani, P.; Fouladvand, A.; Rokni-Zadeh, H.; Changi-Ashtiani, M.; Miryounesi, M.; Puel, A.; Shahrooei, M.; Finocchi, A.; Rossi, P.; Rivalta, B.; Cifaldi, C.; Novelli, A.; Passarelli, C.; Arasi, S.; Bullens, D.; Sauer, K.; Claeys, T.; Biggs, C.M.; Morris, E.C.; Rosenzweig, S.D.; O’Shea, J.J.; Wasserman, W.W.; Bedford, H.M.; van Karnebeek, C.D.M.; Palma, P.; Burns, S.O.; Meyts, I.; Casanova, J.L.; Lyons, J.J.; Parvaneh, N.; Nguyen, A.T.V.; Cancrini, C.; Heimall, J.; Ahmed, H.; McKinnon, M.L.; Lau, Y.L.; Béziat, V.; Turvey, S.E. Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease. J. Exp. Med., 2023, 220(5), e20221755.
[http://dx.doi.org/10.1084/jem.20221755] [PMID: 36884218]
[16]
Abell, N.S.; DeGorter, M.K.; Gloudemans, M.J.; Greenwald, E.; Smith, K.S.; He, Z.; Montgomery, S.B. Multiple causal variants underlie genetic associations in humans. Science, 2022, 375(6586), 1247-1254.
[http://dx.doi.org/10.1126/science.abj5117] [PMID: 35298243]
[17]
Bønnelykke, K.; Sparks, R.; Waage, J.; Milner, J.D. Genetics of allergy and allergic sensitization: Common variants, rare mutations. Curr. Opin. Immunol., 2015, 36, 115-126.
[http://dx.doi.org/10.1016/j.coi.2015.08.002] [PMID: 26386198]
[18]
Tamari, M.; Hirota, T. Genome‐wide association studies of atopic dermatitis. J. Dermatol., 2014, 41(3), 213-220.
[http://dx.doi.org/10.1111/1346-8138.12321] [PMID: 24628071]
[19]
Haider, S.; Simpson, A.; Custovic, A. Genetics of asthma and allergic diseases. Handb. Exp. Pharmacol., 2021, 268, 313-329.
[http://dx.doi.org/10.1007/164_2021_484] [PMID: 34085121]
[20]
Johansson, E.; Mersha, T.B. Genetics of food allergy. Immunol. Allergy Clin. North Am., 2021, 41(2), 301-319.
[http://dx.doi.org/10.1016/j.iac.2021.01.010] [PMID: 33863485]
[21]
Gandhi, C.K.; Chen, C.; Amatya, S.; Yang, L.; Fu, C.; Zhou, S.; Wu, R.; Buendía-Roldan, I.; Selman, M.; Pardo, A.; Floros, J. SNP and haplotype interaction models reveal association of surfactant protein gene polymorphisms with hypersensitivity pneumonitis of mexican population. Front. Med., 2021, 7, 588404.
[http://dx.doi.org/10.3389/fmed.2020.588404] [PMID: 33469544]
[22]
Kılıç, M.; Beyazıt, E.; Önalan, E.E.; Kaymaz, T.; Taşkın, E. Evaluation of toll-like receptors 2 and 4 polymorphism and intestinal microbiota in children with food allergies. Turk. J. Pediatr., 2023, 65(5), 758-768.
[http://dx.doi.org/10.24953/turkjped.2023.389] [PMID: 37853967]
[23]
Wechsler, M.E.; Munitz, A.; Ackerman, S.J.; Drake, M.G.; Jackson, D.J.; Wardlaw, A.J.; Dougan, S.K.; Berdnikovs, S.; Schleich, F.; Matucci, A.; Chanez, P.; Prazma, C.M.; Howarth, P.; Weller, P.F.; Merkel, P.A. Eosinophils in health and disease: A state-of-the-art review. Mayo Clin. Proc., 2021, 96(10), 2694-2707.
[http://dx.doi.org/10.1016/j.mayocp.2021.04.025] [PMID: 34538424]
[24]
Misery, L.; Pierre, O.; Le Gall-Ianotto, C.; Lebonvallet, N.; Chernyshov, P.V.; Le Garrec, R.; Talagas, M. Basic mechanisms of itch. J. Allergy Clin. Immunol., 2023, 152(1), 11-23.
[http://dx.doi.org/10.1016/j.jaci.2023.05.004] [PMID: 37201903]
[25]
Tan, Y.Y.; Zhou, H.Q.; Lin, Y.J.; Yi, L.T.; Chen, Z.G.; Cao, Q.D.; Guo, Y.R.; Wang, Z.N.; Chen, S.D.; Li, Y.; Wang, D.Y.; Qiao, Y.K.; Yan, Y. FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells. Mil. Med. Res., 2022, 9(1), 7.
[http://dx.doi.org/10.1186/s40779-022-00366-3] [PMID: 35093168]
[26]
Zhang, H.; Sun, Y.; Shen, C.; Jin, P.; Yue, W.; Zhang, Q.; Zhu, F.; Zhang, H. Evaluation value of allergy in adenoid hypertrophy through blood inflammatory cells and total immunoglobulin E. Pediatr. Allergy Immunol. Pulmonol., 2022, 35(4), 139-144.
[http://dx.doi.org/10.1089/ped.2022.0114] [PMID: 36473200]
[27]
Meng, Y.; Wang, Y.; Lou, H.; Wang, K.; Meng, N.; Zhang, L.; Wang, C. Specific immunoglobulin E in nasal secretions for the diagnosis of local allergic rhinitis. Rhinology, 2019, 57(4), 313-320.
[http://dx.doi.org/10.4193/Rhin18.292] [PMID: 31129685]
[28]
Gould, H.J.; Sutton, B.J. IgE in allergy and asthma today. Nat. Rev. Immunol., 2008, 8(3), 205-217.
[http://dx.doi.org/10.1038/nri2273] [PMID: 18301424]
[29]
Martinez, F.D. Recognizing early asthma. Allergy, 1999, 54(S49), 24-28.
[http://dx.doi.org/10.1111/j.1398-9995.1999.tb04384.x] [PMID: 10422744]
[30]
Liang, T.; Xu, Y.T.; Zhang, Y.; Cai, P.C.; Hu, L.H. Interleukin-17A and -17F single nucleotide polymorphisms associate with susceptibility of asthma in Chinese Han population. Hum. Immunol., 2018, 79(10), 736-742.
[http://dx.doi.org/10.1016/j.humimm.2018.07.227] [PMID: 30036556]
[31]
Imraish, A.; Abu-Thiab, T.; Alhindi, T.; Zihlif, M. GSDM gene polymorphisms regulate the IgE level in asthmatic patients. PLoS One, 2022, 17(10), e0274951.
[http://dx.doi.org/10.1371/journal.pone.0274951] [PMID: 36201519]
[32]
Lando, V.; Calciano, L.; Minelli, C.; Bombieri, C.; Ferrari, M.; Malerba, G.; Margagliotti, A.; Murgia, N.; Nicolis, M.; Olivieri, M.; Potts, J.; Tardivo, S.; Accordini, S. IL18 gene polymorphism is associated with total IgE in adult subjects with asthma. J. Clin. Med., 2023, 12(12), 3963.
[http://dx.doi.org/10.3390/jcm12123963] [PMID: 37373658]
[33]
Roscioli, E.; Hamon, R.; Ruffin, R.E.; Grant, J.; Hodge, S.; Zalewski, P.; Lester, S. BIRC3 single nucleotide polymorphism associate with asthma susceptibility and the abundance of eosinophils and neutrophils. J. Asthma, 2017, 54(2), 116-124.
[http://dx.doi.org/10.1080/02770903.2016.1196371] [PMID: 27304223]
[34]
El-Husseini, Z.W.; Vonk, J.M.; van den Berge, M.; Gosens, R.; Koppelman, G.H. Association of asthma genetic variants with asthma‐associated traits reveals molecular pathways of eosinophilic asthma. Clin. Transl. Allergy, 2023, 13(4), e12239.
[http://dx.doi.org/10.1002/clt2.12239] [PMID: 37186423]
[35]
Wu, Y.; Zeng, Z.; Guo, Y.; Song, L.; Weatherhead, J.E.; Huang, X.; Zeng, Y.; Bimler, L.; Chang, C.Y.; Knight, J.M.; Valladolid, C.; Sun, H.; Cruz, M.A.; Hube, B.; Naglik, J.R.; Luong, A.U.; Kheradmand, F.; Corry, D.B. Candida albicans elicits protective allergic responses via platelet mediated T helper 2 and T helper 17 cell polarization. Immunity, 2021, 54(11), 2595-2610.e7.
[http://dx.doi.org/10.1016/j.immuni.2021.08.009] [PMID: 34506733]
[36]
Sun, Y.; Vandenbriele, C.; Kauskot, A.; Verhamme, P.; Hoylaerts, M.F.; Wright, G.J. A human platelet receptor protein microarray identifies the high affinity immunoglobulin E receptor subunit (FcR1) as an activating platelet endothelium aggregation receptor 1 (PEAR1) Ligand* S. Mol. Cell. Proteomic., 2015, 14, 1265.
[http://dx.doi.org/10.1074/mcp.M114.046946] [PMID: 25713122]
[37]
Ma, Z.; Paek, D.; Oh, C.K. Plasminogen activator inhibitor‐1 and asthma: Role in the pathogenesis and molecular regulation. Clin. Exp. Allergy, 2009, 39(8), 1136-1144.
[http://dx.doi.org/10.1111/j.1365-2222.2009.03272.x] [PMID: 19438580]
[38]
Williamson, P.; Proudfoot, J.; Gharibans, A.; Dohil, L.; Newbury, R.; Barsamian, J.; Hassan, M.; Rawson, R.; Katzka, D.; Kurten, R.; Dohil, R.; Mousa, H.; Aceves, S. Plasminogen activator inhibitor-1 as a marker of esophageal functional changes in pediatric eosinophilic esophagitis. Clin. Gastroenterol. Hepatol., 2022, 20(1), 57-64.e3.
[http://dx.doi.org/10.1016/j.cgh.2020.09.040] [PMID: 33007513]
[39]
Leija-Martínez, J.J.; Patricio-Román, K.L.; Del-Río-Navarro, B.E.; Villalpando-Carrión, S.; Reyes-Garay, J.A.; Vélez-Reséndiz, J.M.; Romero-Nava, R.; Sanchéz-Muñoz, F.; Villafaña, S.; Muñoz-Hernández, O.; Hong, E.; Ocharan, E.; Huang, F. Retinol-binding protein 4 and plasminogen activator inhibitor-1 as potential prognostic biomarkers of non-allergic asthma caused by obesity in adolescents. Allergol. Immunopathol., 2021, 49(3), 21-29.
[http://dx.doi.org/10.15586/aei.v49i3.73] [PMID: 33938185]
[40]
Jiang, C.; Liu, G.; Cai, L.; Deshane, J.; Antony, V.; Thannickal, V.J.; Liu, R.M. Divergent regulation of alveolar type 2 cell and fibroblast apoptosis by plasminogen activator inhibitor 1 in lung fibrosis. Am. J. Pathol., 2021, 191(7), 1227-1239.
[http://dx.doi.org/10.1016/j.ajpath.2021.04.003] [PMID: 33887217]
[41]
Jin, Z.; Pan, Z.; Wang, Z.; Kong, L.; Zhong, M.; Yang, Y.; Dou, Y.; Sun, J.L. CYSLTR1 rs320995 (T927C) and GSDMB rs7216389 (G1199A) gene polymorphisms in asthma and allergic rhinitis: A proof-of-concept study. J. Asthma Allergy, 2022, 15, 1105-1113.
[http://dx.doi.org/10.2147/JAA.S371120] [PMID: 36034974]
[42]
Wang, Z.; Kong, L.; Luo, G.; Zhang, H.; Sun, F.; Liang, W.; Wu, W.; Guo, Z.; Zhang, R.; Dou, Y. Clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with venous thromboembolism. Thromb. J., 2022, 20(1), 68.
[http://dx.doi.org/10.1186/s12959-022-00430-x] [PMID: 36376889]
[43]
Wang, Z.; Kong, L.; Zhang, H.; Sun, F.; Guo, Z.; Zhang, R.; Dou, Y. Tumor necrosis factor alpha -308G/A gene polymorphisms combined with neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio predicts the efficacy and safety of anti-TNF-α therapy in patients with ankylosing spondylitis, rheumatoid arthritis, and psoriasis arthritis. Front. Pharmacol., 2022, 12, 811719.
[http://dx.doi.org/10.3389/fphar.2021.811719] [PMID: 35126146]
[44]
Tang, R.; Lyu, X.; Li, H.; Sun, J. The 4G/5G polymorphism of plasminogen activator inhibitor type 1 is a predictor of allergic cough. Front. Genet., 2023, 14, 1139813.
[http://dx.doi.org/10.3389/fgene.2023.1139813] [PMID: 36911417]
[45]
Navalpakam, A.; Thanaputkaiporn, N.; Poowuttikul, P. Management of anaphylaxis. Immunol. Allergy Clin. North Am., 2022, 42(1), 65-76.
[http://dx.doi.org/10.1016/j.iac.2021.09.005] [PMID: 34823751]
[46]
Pflipsen, M.C.; Colon, V.K.M. Anaphylaxis: Recognition and management. Am. Fam. Physician, 2020, 102(6), 355-362.
[PMID: 32931210]
[47]
McGrath, F.M.; Francis, A.; Fatovich, D.M.; Macdonald, S.P.J.; Arendts, G.; Woo, A.J.; Bosio, E. Genes involved in platelet aggregation and activation are downregulated during acute anaphylaxis in humans. Clin. Transl. Immunology, 2022, 11(12), e1435.
[http://dx.doi.org/10.1002/cti2.1435] [PMID: 36583159]
[48]
Nie, W.; Li, B.; Xiu, Q. The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: A meta-analysis. PLoS One, 2012, 7(3), e34385.
[http://dx.doi.org/10.1371/journal.pone.0034385] [PMID: 22479620]
[49]
Buč, D.; Hollá, I.L.; Vácha, J. Polymorphism 4G/5G in the plasminogen activator inhibitor‐1 (PAI‐1) gene is associated with IgE‐mediated allergic diseases and asthma in the Czech population. Allergy, 2002, 57(5), 446-448.
[http://dx.doi.org/10.1034/j.1398-9995.2002.03582.x] [PMID: 11972486]
[50]
Okada, K.; Ueshima, S.; Kawao, N.; Yano, M.; Tamura, Y.; Tanaka, M.; Sakamoto, A.; Hatano, M.; Arima, M.; Miyata, S.; Nagai, N.; Tokuhisa, T.; Matsuo, O. Lack of both α2-antiplasmin and plasminogen activator inhibitor type-1 induces high IgE production. Life Sci., 2013, 93(2-3), 89-95.
[http://dx.doi.org/10.1016/j.lfs.2013.05.023] [PMID: 23770230]
[51]
Maison, N.; Omony, J.; Illi, S.; Thiele, D.; Skevaki, C.; Dittrich, A.M.; Bahmer, T.; Rabe, K.F.; Weckmann, M.; Happle, C.; Schaub, B.; Meyer, M.; Foth, S.; Rietschel, E.; Renz, H.; Hansen, G.; Kopp, M.V.; von Mutius, E.; Grychtol, R.; Fuchs, O.; Roesler, B.; Welchering, N.; Kohistani-Greif, N.; Kurz, J.; Landgraf-Rauf, K.; Laubhahn, K.; Liebl, C.; Ege, M.; Hose, A.; Zeitlmann, E.; Berbig, M.; Marzi, C.; Schauberger, C.; Zissler, U.; Schmidt-Weber, C.; Ricklefs, I.; Diekmann, G.; Liboschik, L.; Voigt, G.; Sultansei, L.; Nissen, G.; König, I.R.; Kirsten, A.M.; Pedersen, F.; Watz, H.; Waschki, B.; Herzmann, C.; Abdo, M.; Biller, H.; Gaede, K.I.; Bovermann, X.; Steinmetz, A.; Husstedt, B.L.; Nitsche, C.; Veith, V.; Szewczyk, M.; Brinkmann, F.; Malik, A.; Schwerk, N.; Dopfer, C.; Price, M.; Jirmo, A.C.; Habener, A.; DeLuca, D.S.; Gaedcke, S.; Liu, B.; Calveron, M.R.; Weber, S.; Schildberg, T.; van Koningsbruggen-Rietschel, S.; Alcazar, M. T2-high asthma phenotypes across lifespan. Eur. Respir. J., 2022, 60(3), 2102288.
[http://dx.doi.org/10.1183/13993003.02288-2021] [PMID: 35210326]