Background/Purpose: Anaemia is one of the most common haematological manifestations in SLE patients, occurring in about 50% of active cases. STAT1 is a critical signalling molecule required for the activation of type-1 interferon (I-IFN), CCL2, and CXCL10, all of which are upregulated in SLE. Overexpression of STAT1 has been described as responsible for anaemia in mouse models. CCL2 and CXCL10 are considered as biomarkers for flares. miR-146 has been reported to be downregulated in peripheral monocytes of SLE patients. The aim of this study is to analyze how these components are involved in anaemia in SLE, and what factors can influence their abnormal expression. 

Methods: Blood samples were collected from 30 healthy donors and 100 SLE patients (European Americans (EA) 49; African Americans (AA) 34; Latin Americans (LA) 12; others 5)) fulfilling ACR criteria; 58 patients had samples collected from 2 or more visits. Total RNA, isolated from leukocytes, was analysed by Taqman qPCR. miRNA copy number was determined by a standard curve. Expression of I-IFN signature genes and chemokines were determined by the ΔΔC_T method. Results were correlated with clinical data and analysed by Wilcoxon/Kruskal-Wallis Test and Fisher’s exact test. 

Results:  Comparing biomarker expression in anaemic vs. non-anaemic SLE, we detected a significant increase of IFN score (p<0.0001), STAT1 (p<0.0001), miR-146a (p<0.0004), CCL2 (p<0.0004), and CXCL10 (p<0.015) in the anaemic SLE patients. Lupus Nephritis (LN), one of the most common serious complications in SLE, can be responsible for anaemia. As expected, LN patients are more likely to be anaemic than patients without nephritis (likelihood ratio (LR) =3.7; p<0.024). Anaemic SLE patients displayed significantly higher STAT1, miR-146a, CCL2, and CXCL10 than SLE without anaemia, whether or not nephritis was present. The use of prednisone (PDN) but not mycophenolate and hydroxychloroquine is consistent with more active SLE in our cohort and thus may explain the association of anaemia with PDN. PDN users were more likely to be anaemic (LR= 10.7; p<0.0010).  However, STAT1, miR-146a, CCL2, and CXCL10 were significantly higher in anaemic SLE patients regardless of PDN therapy when compared to those who were not anaemic, whether or not they were on PDN. According to the clinical literature, lupus in AA tends to be more aggressive than in EA.  Similarly, AA were more likely to be anaemic than EA (LR= 8.41; p<0.0032). Both miR-146a and STAT1 were significantly higher in anaemic AA (p<0.019 and p<0.020 respectively) compared to non-anaemic AA. These markers in anaemic EA (p<0.025 and p<0.0065 respectively) were significantly higher than non-anaemic EA. CCL2 was significantly higher in anaemic EA compared to non-anaemic EA, but this was not observed in AA. No significant trend was observed for CXCL10.

Conclusion: Anaemic SLE patients demonstrated a significant increase of STAT1, miR-146a, CCL2, and CXCL10 vs non-anaemic patients. Furthermore LN and PDN did not alter STAT1, miR-146a, CCL2, and CXCL10 in anaemic SLE patients. For ethnic analysis, anaemic AA and EA SLE patients were associated with significantly higher levels of miR-146a and STAT1 that could play a prominent role in anaemia.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/correlation-of-signal-transducers-and-activators-of-transcription-1-and-microrna-146a-with-anaemia-and-other-clinical-features-in-systemic-lupus-erythematosus-patients/