OBJECTIVE: To determine whether disease processes related to granulomatosis with polyangiitis (Wegener's) (GPA) are reflected in gene expression profiles of the nasal mucosa. METHODS: Nasal brushings of the inferior turbinate were obtained from 32 patients with GPA (10 with active nasal disease, 13 with prior nasal disease, and 9 with no history of nasal disease) and a composite comparator group with and without inflammatory nasal disease (12 healthy people, 15 with sarcoidosis, and 8 with allergic rhinitis). Differential gene expression was assessed between subgroups of GPA and comparators. RESULTS: A total of 339 genes were differentially expressed between the GPA and comparator groups (absolute fold change >1.5; false discovery rate <0.05). Top canonical pathways up-regulated in nasal brushings from patients with GPA included granulocyte adhesion and diapedesis (P = 8.6(-22) ), agranulocyte adhesion and diapedesis (P = 1.3(-14) ), IL10 signaling (P = 3.0(-11) ), LXR/RXR activation (P = 4.3(-11) ), and TREM1 signaling (P = 9.0(-11) ). A set of genes differentially expressed in GPA independently of nasal disease activity status included genes related to epithelial barrier integrity (fibronectin 1, desmosomal proteins) and several matricellular proteins (e.g., osteonectin, osteopontin). Significant overlap of differentially expressed genes was observed between active and prior nasal disease GPA subgroups. Peripheral blood neutrophil and mononuclear gene expression levels associated with GPA were similarly altered in the nasal gene expression profiles of patients with active or prior nasal disease. CONCLUSION: Profiling the nasal transcriptome in GPA reveals gene expression signatures related to innate immunity, inflammatory cell chemotaxis, extracellular matrix composition, and epithelial barrier integrity. Thus, airway-based expression profiling is feasible and informative in GPA.
OBJECTIVE: To determine whether disease processes related to granulomatosis with polyangiitis (Wegener's) (GPA) are reflected in gene expression profiles of the nasal mucosa. METHODS: Nasal brushings of the inferior turbinate were obtained from 32 patients with GPA (10 with active nasal disease, 13 with prior nasal disease, and 9 with no history of nasal disease) and a composite comparator group with and without inflammatory nasal disease (12 healthy people, 15 with sarcoidosis, and 8 with allergic rhinitis). Differential gene expression was assessed between subgroups of GPA and comparators. RESULTS: A total of 339 genes were differentially expressed between the GPA and comparator groups (absolute fold change >1.5; false discovery rate <0.05). Top canonical pathways up-regulated in nasal brushings from patients with GPA included granulocyte adhesion and diapedesis (P = 8.6(-22) ), agranulocyte adhesion and diapedesis (P = 1.3(-14) ), IL10 signaling (P = 3.0(-11) ), LXR/RXR activation (P = 4.3(-11) ), and TREM1 signaling (P = 9.0(-11) ). A set of genes differentially expressed in GPA independently of nasal disease activity status included genes related to epithelial barrier integrity (fibronectin 1, desmosomal proteins) and several matricellular proteins (e.g., osteonectin, osteopontin). Significant overlap of differentially expressed genes was observed between active and prior nasal disease GPA subgroups. Peripheral blood neutrophil and mononuclear gene expression levels associated with GPA were similarly altered in the nasal gene expression profiles of patients with active or prior nasal disease. CONCLUSION: Profiling the nasal transcriptome in GPA reveals gene expression signatures related to innate immunity, inflammatory cell chemotaxis, extracellular matrix composition, and epithelial barrier integrity. Thus, airway-based expression profiling is feasible and informative in GPA.
Authors: R Y Leavitt; A S Fauci; D A Bloch; B A Michel; G G Hunder; W P Arend; L H Calabrese; J F Fries; J T Lie; R W Lightfoot Journal: Arthritis Rheum Date: 1990-08
Authors: M Laudien; R Häsler; J Wohlers; J Böck; S Lipinski; L Bremer; R Podschun; P Ambrosch; P Lamprecht; P Rosenstiel; A Till Journal: Mucosal Immunol Date: 2011-03-16 Impact factor: 7.313
Authors: Joshua R Bleharski; Viviane Kiessler; Cecilia Buonsanti; Peter A Sieling; Steffen Stenger; Marco Colonna; Robert L Modlin Journal: J Immunol Date: 2003-04-01 Impact factor: 5.422
Authors: G S Hoffman; G S Kerr; R Y Leavitt; C W Hallahan; R S Lebovics; W D Travis; M Rottem; A S Fauci Journal: Ann Intern Med Date: 1992-03-15 Impact factor: 25.391
Authors: Paul A Lyons; Tim F Rayner; Sapna Trivedi; Julia U Holle; Richard A Watts; David R W Jayne; Bo Baslund; Paul Brenchley; Annette Bruchfeld; Afzal N Chaudhry; Jan Willem Cohen Tervaert; Panos Deloukas; Conleth Feighery; Wolfgang L Gross; Loic Guillevin; Iva Gunnarsson; Lorraine Harper; Zdenka Hrušková; Mark A Little; Davide Martorana; Thomas Neumann; Sophie Ohlsson; Sandosh Padmanabhan; Charles D Pusey; Alan D Salama; Jan-Stephan F Sanders; Caroline O Savage; Mårten Segelmark; Coen A Stegeman; Vladimir Tesař; Augusto Vaglio; Stefan Wieczorek; Benjamin Wilde; Jochen Zwerina; Andrew J Rees; David G Clayton; Kenneth G C Smith Journal: N Engl J Med Date: 2012-07-19 Impact factor: 91.245
Authors: Jaclyn N Taroni; Peter C Grayson; Qiwen Hu; Sean Eddy; Matthias Kretzler; Peter A Merkel; Casey S Greene Journal: Cell Syst Date: 2019-05-22 Impact factor: 10.304
Authors: Sarah K Wise; Sandra Y Lin; Elina Toskala; Richard R Orlandi; Cezmi A Akdis; Jeremiah A Alt; Antoine Azar; Fuad M Baroody; Claus Bachert; G Walter Canonica; Thomas Chacko; Cemal Cingi; Giorgio Ciprandi; Jacquelynne Corey; Linda S Cox; Peter Socrates Creticos; Adnan Custovic; Cecelia Damask; Adam DeConde; John M DelGaudio; Charles S Ebert; Jean Anderson Eloy; Carrie E Flanagan; Wytske J Fokkens; Christine Franzese; Jan Gosepath; Ashleigh Halderman; Robert G Hamilton; Hans Jürgen Hoffman; Jens M Hohlfeld; Steven M Houser; Peter H Hwang; Cristoforo Incorvaia; Deborah Jarvis; Ayesha N Khalid; Maritta Kilpeläinen; Todd T Kingdom; Helene Krouse; Desiree Larenas-Linnemann; Adrienne M Laury; Stella E Lee; Joshua M Levy; Amber U Luong; Bradley F Marple; Edward D McCoul; K Christopher McMains; Erik Melén; James W Mims; Gianna Moscato; Joaquim Mullol; Harold S Nelson; Monica Patadia; Ruby Pawankar; Oliver Pfaar; Michael P Platt; William Reisacher; Carmen Rondón; Luke Rudmik; Matthew Ryan; Joaquin Sastre; Rodney J Schlosser; Russell A Settipane; Hemant P Sharma; Aziz Sheikh; Timothy L Smith; Pongsakorn Tantilipikorn; Jody R Tversky; Maria C Veling; De Yun Wang; Marit Westman; Magnus Wickman; Mark Zacharek Journal: Int Forum Allergy Rhinol Date: 2018-02 Impact factor: 3.858
Authors: James T Rosenbaum; Dongseok Choi; David J Wilson; Hans E Grossniklaus; Christina A Harrington; Cailin H Sibley; Roger A Dailey; John D Ng; Eric A Steele; Craig N Czyz; Jill A Foster; David Tse; Chris Alabiad; Sander Dubovy; Prashant K Parekh; Gerald J Harris; Michael Kazim; Payal J Patel; Valerie A White; Peter J Dolman; Bobby S Korn; Don O Kikkawa; Deepak P Edward; Hind M Alkatan; Hailah al-Hussain; R Patrick Yeatts; Dinesh Selva; Patrick Stauffer; Stephen R Planck Journal: Exp Mol Pathol Date: 2015-07-08 Impact factor: 3.362
Authors: Sehyun Oh; Ludwig Geistlinger; Marcel Ramos; Daniel Blankenberg; Marius van den Beek; Jaclyn N Taroni; Vincent J Carey; Casey S Greene; Levi Waldron; Sean Davis Journal: Nat Commun Date: 2022-06-27 Impact factor: 17.694
Authors: Marcia A Friedman; Dongseok Choi; Stephen R Planck; James T Rosenbaum; Cailin H Sibley Journal: J Rheumatol Date: 2019-01-15 Impact factor: 4.666
Authors: Peter Lamprecht; Anja Kerstein; Sebastian Klapa; Susanne Schinke; Christian M Karsten; Xinhua Yu; Marc Ehlers; Jörg T Epplen; Konstanze Holl-Ulrich; Thorsten Wiech; Kathrin Kalies; Tanja Lange; Martin Laudien; Tamas Laskay; Timo Gemoll; Udo Schumacher; Sebastian Ullrich; Hauke Busch; Saleh Ibrahim; Nicole Fischer; Katrin Hasselbacher; Ralph Pries; Frank Petersen; Gesche Weppner; Rudolf Manz; Jens Y Humrich; Relana Nieberding; Gabriela Riemekasten; Antje Müller Journal: Front Immunol Date: 2018-04-09 Impact factor: 7.561
Authors: Erin E Gill; Maren L Smith; Kristen M Gibson; Kimberly A Morishita; Amy H Y Lee; Reza Falsafi; Jinko Graham; Dirk Foell; Susanne M Benseler; Colin J Ross; Raashid A Luqmani; David A Cabral; Robert E W Hancock; Kelly L Brown Journal: Front Immunol Date: 2021-02-22 Impact factor: 7.561