Defining the nasal transcriptome in granulomatosis with polyangiitis (Wegener's).
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.


CONCLUSIONS
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.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, and Boston University, Boston, Massachusetts.
Peter C
PC
Grayson
Boston University, Boston, Massachusetts.
Katrina
K
Steiling
Boston University, Boston, Massachusetts.
Michael
M
Platt
Boston University, Boston, Massachusetts.
Jeffrey S
JS
Berman
Boston University, Boston, Massachusetts.
Xiaohui
X
Zhang
Boston University, Boston, Massachusetts.
Ji
J
Xiao
Boston University, Boston, Massachusetts.
Yuriy O
YO
Alekseyev
Boston University, Boston, Massachusetts.
Gang
G
Liu
Boston University, Boston, Massachusetts.
Paul A
PA
Monach
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.
Mariana J
MJ
Kaplan
Boston University, Boston, Massachusetts.
Avrum
A
Spira
University of Pennsylvania, Philadelphia, and Boston University, Boston, Massachusetts.
Peter A
PA
Merkel
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002633:Chemotaxis / Q000235:genetics; D051181:Desmosomal Cadherins / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000235:genetics; D020869:Gene Expression Profiling; D014890:Granulomatosis with Polyangiitis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*; D015676:Osteonectin / Q000235:genetics; D053495:Osteopontin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D065631:Rhinitis, Allergic / Q000235:genetics / Q000378:metabolism; D012507:Sarcoidosis / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
D051181:Desmosomal Cadherins; C067625:FN1 protein, human; D005353:Fibronectins; C508609:IL10 protein, human; D015676:Osteonectin; D012333:RNA, Messenger; D053495:Osteopontin; D016753:Interleukin-10