PMID- 34349764
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20231107
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Differentially Expressed Gene Pathways in the Conjunctiva of Sjogren Syndrome 
      Keratoconjunctivitis Sicca.
PG  - 702755
LID - 10.3389/fimmu.2021.702755 [doi]
LID - 702755
AB  - Sjogren syndrome (SS) is an autoimmune condition that targets the salivary and 
      lacrimal glands, with cardinal clinical signs of dry eye (keratoconjunctivitis 
      sicca, KCS) and dry mouth. The conjunctiva of SS patients is often infiltrated by 
      immune cells that participate in the induction and maintenance of local 
      inflammation. The purpose of this study was to investigate immune-related 
      molecular pathways activated in the conjunctiva of SS patients. Female SS 
      patients (n=7) and controls (n=19) completed a series of oral, ocular surface 
      exams. Symptom severity scores were evaluated using validated questionnaires 
      (OSDI and SANDE). All patients fulfilled the ACR/EULAR criteria for SS and the 
      criteria for KCS. Fluorescein and lissamine green dye staining evaluated 
      tear-break-up time (TBUT), corneal and conjunctival disease, respectively. 
      Impression cytology of the temporal bulbar conjunctiva was performed to collect 
      cells lysed and subjected to gene expression analysis using the NanoString 
      Immunology Panel. 53/594 differentially expressed genes (DEGs) were observed 
      between SS and healthy controls; 49 DEGs were upregulated, and 4 were 
      downregulated (TRAF5, TGFBI, KLRAP1, and CMKLRI). The top 10 DEGs in descending 
      order were BST2, IFITM1, LAMP3, CXCL1, IL19, CFB, LY96, MX1, IL4R, CDKN1A. Twenty 
      pathways had a global significance score greater or equal to 2. Spearman 
      correlations showed that 29/49 upregulated DEGs correlated with either TBUT 
      (inverse) or OSDI or conjunctival staining score (positive correlations). Venn 
      diagrams identified that 26/29 DEGs correlated with TBUT, 5/26 DEGs correlated 
      with OSDI, and 16/26 correlated with conjunctival staining scores. Five 
      upregulated DEGs (CFB, CFI, IL1R1, IL2RG, IL4R) were uniquely negatively 
      correlated with TBUT. These data indicate that the conjunctiva of SS patients 
      exhibits a phenotype of immune activation, although some genes could be 
      inhibitory. Some of the DEGs and pathways overlap with previous DEGs in salivary 
      gland biopsies, but new DEGs were identified, and some of these correlated with 
      symptoms and signs of dry eye. Our results indicate that gene analysis of 
      conjunctiva imprints is a powerful tool to understand the pathogenesis of SS and 
      develop new therapeutic targets.
CI  - Copyright (c) 2021 de Paiva, Trujillo-Vargas, Schaefer, Yu, Britton and 
      Pflugfelder.
FAU - de Paiva, Cintia S
AU  - de Paiva CS
AD  - Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United 
      States.
FAU - Trujillo-Vargas, Claudia M
AU  - Trujillo-Vargas CM
AD  - Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United 
      States.
AD  - Center for Metagenomics and Microbiome Research, Department of Molecular Virology 
      and Microbiology, Baylor College of Medicine, Houston, TX, United States.
AD  - Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Universidad de 
      Antioquia UdeA, Medellin, Colombia.
FAU - Schaefer, Laura
AU  - Schaefer L
AD  - Center for Metagenomics and Microbiome Research, Department of Molecular Virology 
      and Microbiology, Baylor College of Medicine, Houston, TX, United States.
FAU - Yu, Zhiyuan
AU  - Yu Z
AD  - Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United 
      States.
FAU - Britton, Robert A
AU  - Britton RA
AD  - Center for Metagenomics and Microbiome Research, Department of Molecular Virology 
      and Microbiology, Baylor College of Medicine, Houston, TX, United States.
FAU - Pflugfelder, Stephen C
AU  - Pflugfelder SC
AD  - Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United 
      States.
LA  - eng
GR  - P30 CA125123/CA/NCI NIH HHS/United States
GR  - P30 DK056338/DK/NIDDK NIH HHS/United States
GR  - P30 EY002520/EY/NEI NIH HHS/United States
GR  - R01 EY026893/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210719
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
SB  - IM
MH  - Adult
MH  - Aged
MH  - Conjunctiva/*immunology
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Sjogren's Syndrome/*immunology
MH  - *Transcriptome
PMC - PMC8326832
OTO - NOTNLM
OT  - Sjogren syndrome
OT  - conjunctiva
OT  - dry eye
OT  - gene expression
OT  - immune pathways
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/08/06 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/01/01
CRDT- 2021/08/05 06:24
PHST- 2021/04/29 00:00 [received]
PHST- 2021/07/01 00:00 [accepted]
PHST- 2021/08/05 06:24 [entrez]
PHST- 2021/08/06 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.702755 [doi]
PST - epublish
SO  - Front Immunol. 2021 Jul 19;12:702755. doi: 10.3389/fimmu.2021.702755. eCollection 
      2021.