Positive Correlation of STAT1 and miR-146a with Anemia in Patients with Systemic Lupus Erythematosus
- 454 Downloads
Anemia is one of the most common hematological manifestations in SLE patients, occurring in about 50 % of active cases. STAT1 is a critical signaling molecule required for the production of type-1 interferon (I-IFN), CCL2, and CXCL10, all of which are upregulated in SLE. Overexpression of STAT1 has been described to be involved in anemia in animal models. The aim of this study is to analyze how these components are involved in SLE-associated anemia.
Blood samples were collected from 39 healthy donors and 101 SLE patients fulfilling ACR criteria. Samples were collected from a total of 180 visits (58 patients had 2 or more visits) of which 52 visits included a diagnosis of anemia. Healthy donors had only single visit. Total RNA, isolated from leukocytes, was analyzed by Taqman qPCR. Relative expression levels of I-IFN signature genes, chemokines, and miR-146a were determined by the ΔΔCT method. Results were correlated with clinical data and analyzed by the Wilcoxon/Kruskal-Wallis test and Fisher’s exact test.
Significant increases in IFN score (p < 0.0001), STAT1 (p < 0.0001), miR-146a (p < 0.0005), CCL2 (p = 0.0047), and CXCL10 (p = 0.017), as well as a significant decrease in pri-miR-146a (p = 0.0002), were detected in the anemic SLE patient visits (n = 52) compared to non-anemic SLE visits (n = 128). Regardless of disease activity, lupus nephritis, or race, anemic SLE patients displayed significantly elevated levels of STAT1 and miR-146a compared to non-anemic SLE patients.
STAT1 and miR-146a may be upregulated during inflammation and via proinflammatory cytokines and chemokines in SLE. Prolonged upregulation of STAT1 and miR-146a appears to play an important role in anemia in SLE patients.
KeywordsAnemia CCL2 CXCL10 miR-146a lupus
C-C motif chemokine ligand 2
C-X-C motif chemokine 10
Systemic lupus erythematosus
SLE disease activity index
Signal transducers and activators of transcription 1
We thank all the staff at the Division of Rheumatology for collection of blood and clinical information. This work was supported in part by a grant from the Lupus Research Institute and the National Institutes of Health grant Al47859. PRDG was supported by training grant T90/R90 DE007200.
The authors declare that they have no conflicts of interest.
- 9.Usacheva A, Smith R, Minshall R, Baida G, Seng S, Croze E, et al. The WD motif-containing protein receptor for activated protein kinase C (RACK1) is required for recruitment and activation of signal transducer and activator of transcription 1 through the type I interferon receptor. J Biol Chem. 2001;276:22948–53.PubMedCrossRefGoogle Scholar
- 25.The American College of Rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials. Arthritis Rheum. 2006;54:421-32.Google Scholar