title: Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling.
abstract: Biopsies and ANCA testing for limited forms of granulomatosis with polyangiitis (GPA) are frequently non-diagnostic. We characterized gene expression in GPA and other causes of orbital inflammation. We tested the hypothesis that a sub-set of patients with non-specific orbital inflammation (NSOI, also known as pseudotumor) mimics a limited form of GPA. Formalin-fixed, paraffin-embedded orbital biopsies were obtained from controls (n=20) and patients with GPA (n=6), NSOI (n=25), sarcoidosis (n=7), or thyroid eye disease (TED) (n=20) and were divided into discovery and validation sets. Transcripts in the tissues were quantified using Affymetrix U133 Plus 2.0 microarrays. Distinct gene expression profiles for controls and subjects with GPA, TED, or sarcoidosis were evident by principal coordinate analyses. Compared with healthy controls, 285 probe sets had elevated signals in subjects with GPA and 1472 were decreased (>1.5-fold difference, false discovery rate adjusted p<0.05). The immunoglobulin family of genes had the most dramatic increase in expression. Although gene expression in GPA could be readily distinguished from gene expression in TED, sarcoidosis, or controls, a comparison of gene expression in GPA versus NSOI found no statistically significant differences. Thus, forms of orbital inflammation can be distinguished based on gene expression. NSOI/pseudotumor is heterogeneous but often may be an unrecognized, localized form of GPA.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA; Devers Eye Institute, Legacy Health Systems, Portland, OR 97210, USA. Electronic address: rosenbaj@ohsu.edu.
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA; Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: choid@ohsu.edu.
authors.forename: Dongseok
authors.initials: D
authors.lastname: Choi
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: wilsonda@ohsu.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilson
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA. Electronic address: ophtheg@emory.edu.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
authors.affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: harringc@ohsu.edu.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Harrington
authors.affiliation: Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: Sibleyc@ohsu.edu.
authors.forename: Cailin H
authors.initials: CH
authors.lastname: Sibley
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: daileyr@ohsu.edu.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Dailey
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: ngj@ohsu.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Ng
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: steeleer@ohsu.edu.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Steele
authors.affiliation: Division of Ophthalmology, Ohio University, Columbus, OH 43228, USA. Electronic address: dsp4000@aol.com.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Czyz
authors.affiliation: Department of Ophthalmology, The Ohio State University, Columbus, OH 43215, USA. Electronic address: fosterj@jillfoster.om.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Foster
authors.affiliation: Department of Ophthalmology, University of Miami, FL 33101, USA. Electronic address: dtse@med.miami.edu.
authors.forename: David
authors.initials: D
authors.lastname: Tse
authors.affiliation: Department of Ophthalmology, University of Miami, FL 33101, USA. Electronic address: calabiad@med.miami.edu.
authors.forename: Chris
authors.initials: C
authors.lastname: Alabiad
authors.affiliation: Department of Ophthalmology, University of Miami, FL 33101, USA. Electronic address: sdubovy@med.miami.edu.
authors.forename: Sander
authors.initials: S
authors.lastname: Dubovy
authors.affiliation: Department of Ophthalmology, University of Miami, FL 33101, USA. Electronic address: prashant-parekh@uiowa.edu.
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Parekh
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: GJharris@mcw.edu.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Harris
authors.affiliation: Department of Ophthalmology, Columbia University, New York, NY 10032, USA. Electronic address: mk48@columbia.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Kazim
authors.affiliation: Department of Ophthalmology, Columbia University, New York, NY 10032, USA. Electronic address: ppatel811@gmail.com.
authors.forename: Payal J
authors.initials: PJ
authors.lastname: Patel
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia V5Z 3N9, Canada. Electronic address: Val.White@vch.ca.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: White
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia V5Z 3N9, Canada. Electronic address: peterdolman@hotmail.com.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dolman
authors.affiliation: Department of Ophthalmology, University of California, San Diego, CA 92037, USA. Electronic address: bkorn@ucsd.edu.
authors.forename: Bobby S
authors.initials: BS
authors.lastname: Korn
authors.affiliation: Department of Ophthalmology, University of California, San Diego, CA 92037, USA. Electronic address: dkikkawa@ucsd.edu.
authors.forename: Don O
authors.initials: DO
authors.lastname: Kikkawa
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia. Electronic address: dedward@kkesh.med.sa.
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Edward
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia. Electronic address: hindkatan@yahoo.com.
authors.forename: Hind M
authors.initials: HM
authors.lastname: Alkatan
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia. Electronic address: hhussain@kkesh.med.sa.
authors.forename: Hailah
authors.initials: H
authors.lastname: al-Hussain
authors.affiliation: Department of Ophthalmology, Wake Forrest University, Winston-Salem, NC 27103, USA. Electronic address: pyeatts@wfubmc.edu.
authors.forename: R Patrick
authors.initials: RP
authors.lastname: Yeatts
authors.affiliation: Ophthalmology Network, Royal Adelaide Hospital, Adelaide 5000, Australia. Electronic address: saioph@gmail.com.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Selva
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: stauffep@ohsu.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Stauffer
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA; Devers Eye Institute, Legacy Health Systems, Portland, OR 97210, USA. Electronic address: plancks@ohsu.edu.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Planck
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D014890:Granulomatosis with Polyangiitis / Q000235:genetics* / Q000473:pathology; D049970:Graves Ophthalmopathy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016727:Orbital Pseudotumor / Q000235:genetics* / Q000473:pathology; D012507:Sarcoidosis / Q000235:genetics* / Q000473:pathology
chemical_list: D015415:Biomarkers
keywords: Gene expression profiling; Granulomatosis with polyangiitis; Microarray analysis; Molecular pathology; Orbit pathology; Orbital pseudotumor