title: Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood.
abstract: OBJECTIVE
  Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy.
  
  
  OBJECTIVE
  To determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis.
  
  
  METHODS
  In a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis.
  
  
  METHODS
  Significantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P < .05.
  
  
  RESULTS
  Signals from 2449 probe sets (transcripts from approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and 67 probe sets (approximately 56 genes) had significantly lower signals in both orbital tissues and in peripheral blood from patients with sarcoidosis. The transcription factors, interferon-response factor 1, interferon-response factor 2, and nuclear factor κB, were strongly implicated in the expression of messenger RNA upregulated in common in the 3 tissues.
  
  
  CONCLUSIONS
  Gene expression in sarcoidosis involving the orbit or lacrimal gland can be distinguished from gene expression patterns in control tissue and overlaps with many transcripts upregulated or downregulated in the peripheral blood of patients with sarcoidosis. These observations suggest that common pathogenic mechanisms contribute to sarcoidosis in different sites. The observations support the hypothesis that a pattern of gene expression profiles could provide diagnostic information in patients with sarcoidosis.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland2Department of Medicine, School of Medicine, Oregon Health & Science University, Portland3Devers Eye Institute, Legacy Health Systems, Portland, Oregon.
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland4Department of Public Health and Preventive Medicine, School of Medicine, Oregon Health & Science University, Portland.
authors.forename: Dongseok
authors.initials: D
authors.lastname: Choi
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilson
authors.affiliation: Department of Ophthalmology, Emory School of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
authors.affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Harrington
authors.affiliation: Department of Medicine, School of Medicine, Oregon Health & Science University, Portland.
authors.forename: Cailin H
authors.initials: CH
authors.lastname: Sibley
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Dailey
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: John D
authors.initials: JD
authors.lastname: Ng
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Steele
authors.affiliation: Division of Ophthalmology, Ohio University, Athens.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Czyz
authors.affiliation: Department of Ophthalmology, College of Medicine and Public Health, The Ohio State University, Columbus.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Foster
authors.affiliation: Department of Ophthalmology, Miller School of Medicine, University of Miami, Miami, Florida.
authors.forename: David
authors.initials: D
authors.lastname: Tse
authors.affiliation: Department of Ophthalmology, Miller School of Medicine, University of Miami, Miami, Florida.
authors.forename: Chris
authors.initials: C
authors.lastname: Alabiad
authors.affiliation: Department of Ophthalmology, Miller School of Medicine, University of Miami, Miami, Florida.
authors.forename: Sander
authors.initials: S
authors.lastname: Dubovy
authors.affiliation: Department of Ophthalmology, Miller School of Medicine, University of Miami, Miami, Florida.
authors.forename: Prashant
authors.initials: P
authors.lastname: Parekh
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Harris
authors.affiliation: Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York.
authors.forename: Michael
authors.initials: M
authors.lastname: Kazim
authors.affiliation: Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York.
authors.forename: Payal
authors.initials: P
authors.lastname: Patel
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: White
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Dolman
authors.affiliation: Department of Ophthalmology, School of Medicine, University of California, San Diego.
authors.forename: Bobby S
authors.initials: BS
authors.lastname: Korn
authors.affiliation: Department of Ophthalmology, School of Medicine, University of California, San Diego.
authors.forename: Don
authors.initials: D
authors.lastname: Kikkawa
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Edward
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Hind
authors.initials: H
authors.lastname: Alkatan
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Hailah
authors.initials: H
authors.lastname: Al-Hussain
authors.affiliation: Department of Ophthalmology, School of Medicine, Wake Forrest University, Winston-Salem, North Carolina.
authors.forename: R Patrick
authors.initials: RP
authors.lastname: Yeatts
authors.affiliation: Ophthalmology Network, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Selva
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Stauffer
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland2Department of Medicine, School of Medicine, Oregon Health & Science University, Portland3Devers Eye Institute, Legacy Health Systems, Portland, Oregon.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Planck
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D016022:Case-Control Studies; D005128:Eye Diseases / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D038622:Internationality; D007765:Lacrimal Apparatus / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009915:Orbit; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D012507:Sarcoidosis / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D012680:Sensitivity and Specificity; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger