Association of elevated transcript levels of interferon-inducible chemokines with disease activity and organ damage in systemic lupus erythematosus patients.
BACKGROUND
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with a heterogeneous course and varying degrees of severity and organ damage; thus, there is increasing interest in identifying biomarkers for SLE. In this study we correlated the combined expression level of multiple interferon-inducible chemokines with disease activity, degree of organ damage and clinical features in SLE, and we investigated their roles as biomarkers.


METHODS
Peripheral blood cells obtained from 67 patients with SLE patients, 20 patients with rheumatoid arthritis (RA) and 23 healthy donors were subjected to real-time PCR in order to measure the transcriptional levels of seven interferon-inducible chemokines (RANTES, MCP-1, CCL19, MIG, IP-10, CXCL11, and IL-8). The data were used to calculate a chemokine score for each participant, after which comparisons were performed between various groups of SLE patients and control individuals.


RESULTS
Chemokine scores were significantly elevated in SLE patients versus RA patients and healthy donors (P = 0.012 and P = 0.002, respectively). Chemokine scores were correlated positively with SLE Disease Activity Index 2000 scores (P = 0.005) and negatively with C3 levels (P < 0.001). Compared with patients without lupus nephritis and those with inactive lupus nephritis, chemokine scores were elevated in patients with active lupus nephritis, especially when their daily prednisone dosage was under 30 mg (P = 0.002 and P = 0.014, respectively). Elevated chemokine scores were also associated with the presence of cumulative organ damage (Systemic Lupus International Collaborating Clinics/American Society of Rheumatology Damage Index >or= 1; P = 0.010) and the occurrence of anti-Sm or anti-RNP autoantibodies (both P = 0.021).


CONCLUSIONS
The combined transcription level of interferon-inducible chemokines in peripheral blood leucocytes is closely associated with disease activity, degree of organ damage, and specific autoantibody patterns in SLE. The chemokine score may serve as a new biomarker for active and severe disease in SLE.
Fu
Qiong
Q
Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shan Dong Middle Road, Shanghai 200001, PR China. derafu@hotmail.com
Chen
Xiaoqing
X
Cui
Huijuan
H
Guo
Yanzhi
Y
Chen
Jing
J
Shen
Nan
N
Bao
Chunde
C
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D018925:Chemokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D007962:Leukocytes; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D018925:Chemokines; D007372:Interferons
Methods Mol Med. 2004;102:129-54
15286384
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2610-5
12604793
J Immunol. 2008 Feb 1;180(3):1938-47
18209092
Biochim Biophys Acta. 1999 Jul 7;1446(1-2):167-72
10395932
Ann Rheum Dis. 2006 Feb;65(2):209-15
15975968
J Immunol. 2007 Jan 1;178(1):253-61
17182562
Am J Pathol. 2001 Jul;159(1):237-43
11438470
J Rheumatol. 2002 Feb;29(2):288-91
11838846
Arthritis Rheum. 2007 May;56(5):1658-68
17469160
Cytokine. 2000 Oct;12(10):1561-5
11023674
J Immunol. 1997 Jul 1;159(1):401-8
9200479
J Am Soc Nephrol. 2001 Jul;12(7):1369-1382
11423566
Ann Rheum Dis. 2007 Aug;66(8):1008-14
17223656
Exp Dermatol. 2007 May;16(5):454-63
17437489
Arthritis Rheum. 1988 Mar;31(3):315-24
3358796
Arthritis Rheum. 1996 Mar;39(3):363-9
8607884
FEBS Lett. 2002 Jan 30;511(1-3):41-5
11821046
Clin Exp Immunol. 2006 Jul;145(1):190-9
16792690
J Exp Med. 1996 Sep 1;184(3):963-9
9064356
Arthritis Rheum. 2005 May;52(5):1491-503
15880830
Clin Rheumatol. 2007 May;26(5):718-22
16924394
Arthritis Rheum. 1982 Nov;25(11):1271-7
7138600
J Interferon Res. 1994 Dec;14(6):357-63
7897255
Arthritis Rheum. 2006 Jun;54(6):1906-16
16736505
Arthritis Rheum. 2003 Sep;48(9):2555-66
13130475
Arthritis Rheum. 2004 Dec;50(12):3958-67
15593221
Arthritis Rheum. 2006 Sep;54(9):2951-62
16947629
Genes Immun. 2003 Apr;4(3):177-86
12700592
Immunology. 2004 Jun;112(2):301-9
15147573
Annu Rev Immunol. 2000;18:217-42
10837058
Rheumatology (Oxford). 2004 Sep;43(9):1121-8
15213333
Clin Immunol. 2002 Mar;102(3):283-90
11890715
Hum Immunol. 2002 Dec;63(12):1172-80
12480261
PLoS Med. 2006 Dec;3(12):e491
17177599
Lupus. 2001;10(7):484-90
11480846
J Exp Med. 2003 Mar 17;197(6):711-23
12642603