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Positive Correlation of STAT1 and miR-146a with Anemia in Patients with Systemic Lupus Erythematosus

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

AA:

African Americans

AsA:

Asian Americans

CCL2:

C-C motif chemokine ligand 2

CXCL10:

C-X-C motif chemokine 10

EA:

European Americans

HCQ:

Hydroxychloroquine

I-IFN:

Type-1 interferon

IFNAR:

Interferon receptor

LA:

Latino Americans

LN:

Lupus nephritis

MA:

Multiethnic Americans

MMF:

Mycophenolate mofetil

PDN:

Prednisone

SLE:

Systemic lupus erythematosus

SLEDAI:

SLE disease activity index

STAT1:

Signal transducers and activators of transcription 1

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Acknowledgments

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.

Disclosures

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Oral Biology, University of Florida, 1395 Center Drive, Gainesville, FL, 32610-0424, USA

    Paul R. Dominguez-Gutierrez, Angela Ceribelli & Edward K. L. Chan

  2. Department of Medicine, University of Florida, 1600 SW Archer Rd., Gainesville, FL, 32610-0221, USA

    Minoru Satoh, Eric S. Sobel & Westley H. Reeves

  3. BIOMETRA Department, University of Milan, Milan, Italy

    Angela Ceribelli

  4. School of Health Sciences, University of Occupational and Environmental Health, Japan, 1-1 Isei-ga-oka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan

    Minoru Satoh

  5. Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Via A. Manzoni 56, 20089, Rozzano, Italy

    Angela Ceribelli

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  1. Paul R. Dominguez-Gutierrez
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  2. Angela Ceribelli
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  3. Minoru Satoh
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  4. Eric S. Sobel
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Correspondence to Edward K. L. Chan.

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Dominguez-Gutierrez, P.R., Ceribelli, A., Satoh, M. et al. Positive Correlation of STAT1 and miR-146a with Anemia in Patients with Systemic Lupus Erythematosus. J Clin Immunol 34, 171–180 (2014). https://doi.org/10.1007/s10875-013-9973-3

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  • DOI: https://doi.org/10.1007/s10875-013-9973-3

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