Elevated levels of soluble humanleukocyte antigen-G in the airways are a marker for a low-inflammatory endotype of asthma

Previous studies have suggested that markers of TH2-associated inflammation in asthma predict clinical responsiveness or resistance to corticosteroid therapy.8,9 We therefore used gene expression data in a subset of the 56 patients with asthma with RNA-seq data to determine TH2-high and TH2-low status defined by ±2 SD of mean values in control subjects and confirmed by hierarchical clustering (Fig 1, C). [...]in our study, sHLA-G levels were highest in patients with asthma with a low TH2 gene score. [...]rather than influencing asthma susceptibility per se, sHLA-G may be a modifier of disease severity and a marker of a distinct clinical endotype characterized by less airway inflammation. Supplementary data 1 T. Fujii, A. Ishitani, D.E. Geraghty, A soluble form of the HLA-G antigen is encoded by a messenger ribonucleic acid containing intron 4, J Immunol, Vol. 153, 1994, 5516-5524 2 A. Ishitani, D.E. Geraghty, Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens, Proc Natl Acad Sci U S A, Vol. 89, 1992, 3947-3951 3 D. Nicolae, N.J. Cox, L.A. Lester, D. Schneider, Z. Tan, C. Billstrand, Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21, Am J Hum Genet, Vol. 76, 2005, 349-357 4 F. Tahan, T. Patiroglu, Plasma soluble human leukocyte antigen G levels in asthmatic children, Int Arch Allergy Immunol, Vol. 141, 2006, 213-216 5 S.R. White, D.A. Loisel, J.F. McConville, R. Stern, Y. Tu, B.A. Marroquin, Levels of soluble human leukocyte antigen-G are increased in asthmatic airways, Eur Respir J, Vol. 35, 2010, 925-927 6 Z. Tan, G. Randall, J. Fan, B. Camoretti-Mercado, R. Brockman-Schneider, L. Pan, Allele-specific targeting of microRNAs to HLA-G and risk of asthma, Am J Hum Genet, Vol. 81, 2007, 829-834 7 N. Rouas-Freiss, A. Naji, A. Durrbach, E.D. Carosella, Tolerogenic functions of human leukocyte antigen G: from pregnancy to organ and cell transplantation, Transplantation, Vol. 84, Iss. 1 Suppl, 2007, S21-5 8 P.G. Woodruff, B. Modrek, D.F. Choy, G. Jia, A.R. Abbas, A. Ellwanger, T-helper type 2-driven inflammation defines major subphenotypes of asthma, Am J Respir Crit Care Med, Vol. 180, 2009, 388-395 9 M.C. Peters, Z.K. Mekonnen, S. Yuan, N.R. Bhakta, P.G. Woodruff, J.V. Fahy, Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma, J Allergy Clin Immunol, Vol. 133, 2014, 388-394 10 J.