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Open Access Research article

Reduced levels of CCL2 and CXCL10 in systemic lupus erythematosus patients under treatment with prednisone, mycophenolate mofetil, or hydroxychloroquine, except in a high STAT1 subset

Paul R Dominguez-Gutierrez16, Angela Ceribelli145, Minoru Satoh23, Eric S Sobel2, Westley H Reeves2 and Edward KL Chan1*

Author Affiliations

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

2 Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Isei-ga-oka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan

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

4 Current address: Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Via A. Manzoni 56, 20089 Rozzano, Italy

5 Current address: BIOMETRA Department, University of Milan, Via Festa del Perdono, 7, 20122 Milan, Italy

6 Current address: Department of Urology, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0247, USA

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Arthritis Research & Therapy 2014, 16:R23  doi:10.1186/ar4451

Published: 24 January 2014

Abstract

Introduction

Our recent data showed that signal transducers and activators of transcription 1 (STAT1), adenosine deaminase acting on RNA (ADAR), C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine 10 (CXCL10) were significantly elevated in a systemic lupus erythematosus (SLE) cohort compared to healthy donors. High and low STAT1 subsets were identified in SLE patient visits. The present study analyzed the correlation of common treatments used in SLE with the levels of these biomarkers.

Methods

Peripheral blood leukocytes were collected from 65 healthy donors and 103 SLE patients, of whom 60 had samples from two or more visits. Total RNA was isolated and analyzed for the expression of mRNA and microRNA using Taqman real-time polymerase chain reaction (PCR) assays. Relative expression of interferon signature genes, CCL2, and CXCL10 were determined by the ΔΔCT method. Results were correlated with therapy using prednisone, mycophenolate mofetil, and hydroxychloroquine and analyzed by Wilcoxon/Kruskal-Wallis test and Fisher’s exact test.

Results

CCL2 and CXCL10 were significantly higher in untreated patients compared to treated patients, however, in high STAT1 patient visits there is no significant difference between treated and untreated patients’ visits. When comparing linear regression fits of interferon (IFN) score with CCL2 and CXCL10, untreated patients and high STAT1 patients displayed significantly higher slopes compared to treated patients. There was no significant difference between the slopes of high STAT1 and untreated patients indicating that CCL2 and CXCL10 were correlated with type-I IFN in high STAT1 patients similar to that in untreated patients. CCL2 and CXCL10 levels in the high STAT1 subset remained high in treated patient visits compared to those of the low STAT1 subset.

Conclusions

Among the biomarkers analyzed, only CCL2 and CXCL10 showed significantly reduced levels in treated compared to untreated SLE patients. STAT1, CCL2, and CXCL10 are potentially useful indicators of therapeutic action in SLE patients. Further work is needed to determine whether high STAT1 levels convey resistance to therapies commonly used to treat SLE and whether STAT1 inhibitors may have therapeutic implication for these patients.