Elevated signal transducers and activators of transcription 1 correlates with increased C-C motif chemokine ligand 2 and C-X-C motif chemokine 10 levels in peripheral blood of patients with systemic lupus erythematosus.
BACKGROUND
The present study examines the levels of recently reported biomarkers, adenosine deaminase acting on RNA (ADAR), C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine 10 (CXCL10), signal transducers and activators of transcription 1 (STAT1), and miR-146a in systemic lupus erythematosus (SLE) patients over multiple visits.


METHODS
Peripheral blood leukocytes were collected from 65 healthy donors and 103 SLE patients, 60 of whom had samples from 2 or more visits. Total RNA was isolated and analyzed for the expression of mRNA and microRNA using Taqman real time PCR assays. Relative expression of I-IFN signature genes, chemokines, and miR-146a were determined by the ΔΔCT method. Results were correlated with clinical data and analyzed by Wilcoxon/Kruskal-Wallis test and Fisher's exact test.


RESULTS
Levels of ADAR, CCL2, CXCL10, and STAT1 in SLE were significantly elevated compared with the healthy controls (P <0.0001). ADAR, CCL2, and CXCL10 showed significant correlation with IFN score in both healthy donors (P <0.0033) and SLE patients (P <0.0001). In SLE patients, miR-146a level was not significantly different from healthy controls nor correlated to the IFN score. Two STAT1 populations were identified: a low STAT1 and a high STAT1 group. High STAT1 patient visits displayed higher (P ≤0.0020) levels of CCL2 and CXCL10 than the low STAT1 patient visits. STAT1 levels correlated with IFN score in low STAT1 group but not in high STAT1 group. More importantly, high STAT1 levels appeared as an enhancer of CCL2 and CXCL10 as indicated by the significantly stronger correlation of CCL2 and CXCL10 with IFN score in high STAT1 patient visits relative to low STAT1 patient visits.


CONCLUSIONS
Our data indicate a novel role for STAT1 in the pathogenesis of SLE as an expression enhancer of CCL2 and CXCL10 in SLE patients with high levels of STAT1. Future study is needed to examine the exact role of STAT1 in the etiology of SLE.
Paul R
PR
Dominguez-Gutierrez
Angela
A
Ceribelli
Minoru
M
Satoh
Eric S
ES
Sobel
Westley H
WH
Reeves
Edward K L
EK
Chan
D000243:Adenosine Deaminase / Q000097:blood; D000328:Adult; D000368:Aged; D018932:Chemokine CCL2 / Q000097:blood*; D054357:Chemokine CXCL10 / Q000097:blood*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D008297:Male; D035683:MicroRNAs / Q000097:blood; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000097:blood*
C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C000595356:ADAR protein, human; D000243:Adenosine Deaminase