Increased expression of the type I interferon-inducible gene,lymphocyte antigen 6 complex locus E,in peripheral blood cells is predictive of lupus activity in a large cohort of Chinese lupus patients
Restricted accessResearch articleFirst published online September, 2008
Increased expression of the type I interferon-inducible gene,lymphocyte antigen 6 complex locus E,in peripheral blood cells is predictive of lupus activity in a large cohort of Chinese lupus patients
Several studies by microarray analysis and real-time polymerase chain reaction (RT-PCR) reveal that type I interferon-inducible genes (IFIGs) are implicated in systemic lupus erythematosus (SLE). To find a potential clinical biomarker capable of monitoring lupus disease activity clinically, quantitative RT-PCR was used to identify transcript expression levels of 13 type I IFIGs in peripheral blood cells in 144 patients with SLE, 27 non-SLE patients and 60 healthy controls and then analyse connections between gene expression and disease activity. The expression levels of five type I IFIGs (LY6E, OAS3, IFIT4, OAS1 and OAS2) were significantly higher in the SLE group than in the healthy and non-SLE controls. LY6E gene that had highest expression was chosen to analyse the association of expression level with clinical features. Compared to low LY6E expression group, SLE patients with high LY6E expression had higher SLEDAI-2K score, increased 24 h urine protein and lower blood C3 complement. Active SLE patients had more elevated LY6E expression than stable patients. And LY6E expression levels in patients with SLE were strongly correlated with their SLEDAI-2K scores. Our results indicate that increased expression of LY6E gene in peripheral blood cells in patients with SLE is correlated with lupus activity and may be a useful, noninvasive biomarker for assessing SLE disease activity.
1 Merrill JT Buyon JP . The role of biomarkers in the assessment of lupus.Best Pract Res Clin Rheumatol2005; 19: 709–726.
2.
2 Bengtsson AA Sturfelt G Truedsson L . Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies.Lupus2000; 9: 664–671.
3.
3 Braun D Geraldes P Demengeot J . Type I Interferon controls the onset and severity of autoimmune manifestations in lpr mice.J Autoimmun2003; 20: 15–25.
4.
4 Mathian A Weinberg A Gallegos M Banchereau J Koutouzov S . IFN-α induces early lethal lupus in preautoimmune (New Zealand Black × New Zealand White)F1 but not in BALB/c mice.J Immunol2005; 174: 2499–2506.
5.
5 Baechler EC Batliwalla FM Karypis G . Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus.Proc Natl Acad Sci USA2003; 100: 2610–2615.
6.
6 Han GM Chen SL Shen N Ye S Bao CD Gu YY . Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray.Genes Immun2003; 4: 177–186.
7.
7 Petri M Tesfasyone H Singh S . The systemic lupus erythematosus interferon signature is associated with current activity and is also predictive of hematologic and mucocutaneous disease activity at the next visit[abstract ]. Arthritis Rheum2005; 52(Suppl. 9): S4–S64.
8.
8 Crow MK Kirou KA Wohlgemuth J . Microarray analysis of gene expression in SLE.Autoimmunity2003; 36: 481–490.
9.
9 Bennett L Palucka AK Arce E . Interferon and granulopoiesis signatures in systemic lupus erythematosus blood.J Exp Med2003; 197: 711–723.
10.
10 Kirou KA Lee C George S . Coordinate overexpression of interferon-α induced genes in systemic lupus erythematosus.Arthritis Rheum2004; 50: 3958–3967.
11.
11 Kirou KA Lee C George S Louca K Peterson MG Crow MK . Activation of the interferon-α pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease.Arthritis Rheum2005; 52: 1491–1503.
12.
12 Feng X Wu H Grossman JM . Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus.Arthritis Rheum2006; 54: 2951–2962.
13.
13 Hochberg MC . for the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology.Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum1997; 40: 1725[Q4].
14.
14 Arnett FC Edworthy SM Bloch DA . The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.Arthritis Rheum1988; 31: 315–324.
15.
15 Gladman DD Ibanez D Urowitz MB . Systemic lupus erythematosus disease activity index 2000.J Rheumatol2002; 29: 288–291.
16.
16 Hartmann R Olsen HS Widder S Jorgensen R Justesen J . p59OASL, a 2’,5’-oligoadenylate synthetase like protein: a novel human gene related to the 2’,5’-oligoadenylate synthetase family.Nucleic Acids Res1998; 26: 4121–4128.
17.
17 Yu M Tong JH Mao M . Cloning of a gene (RIG-G) associated with retinoic acid-induced differentiation of acute promyelocytic leukemia cells and representing a new member of a family of interferon-stimulated genes.Proc Natl Acad Sci USA1997; 94: 7406–7411.
18.
18 Ye S Pang H Gu YY . Protein interaction for an interferon-inducible systemic lupus associated gene, IFIT1.Rheumatology (Oxford)2003; 42: 1155–1163.
19.
19 Ye S Guo Q Tang JP Yang CD Shen N Chen SL . Could 2'5'-oligoadenylate synthetase isoforms be biomarkers to differentiate between disease flare and infection in lupus patients? A pilot study.Clin Rheumatol2007; 26: 186–190.
20.
20 Greenberg SA Pinkus JL Pinkus GS . Interferon-alpha/ beta- mediated innate immune mechanisms in dermatomyositis.Ann Neurol2005; 57: 664–678.
21.
21 Tian L Greenberg SA Kong SW Altschuler J Kohane IS Park PJ . Discovering statistically significant pathways in expression profiling studies.Proc Natl Acad Sci USA2005; 102: 13544–13549.
22.
22 Bave U Nordmark G Lovgren T . Activation of the type I interferon system in primary Sjongren ’s syndrome: a possible etiopathogenic mechanism.Arthritis Rheum2005; 52: 1185–1195.
23.
23 Mondini M Vidali M Airò P . Role of the interferon-inducible gene IFI16 in the etiopathogenesis of systemic autoimmune disorders.Ann N Y Acad Sci2007; 1110: 47–56.
24.
24 Santiago-Raber ML Baccala R Haraldsson KM Choubey D Stewart TA Theofilopoulos AN . Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice.J Exp Med2003; 197: 777–788.
25.
25 Niewold TB Swedler WI . Systemic lupus erythematosus arising during interferon-α therapy for cryoglobulinemic vasculitis associated with hepatitis C.Clin Rheumatol2005; 24: 178–181.
26.
26 Ronnblom L Eloranta ML Alm GV . Role of natural interferon-producing cells (plasmacytoid dendritic cells) in autoimmunity.Autoimmunity2003; 36: 463–472.
27.
27 Hueber W Zeng D Strober S Utz PJ . Interferon-alpha-inducible proteins are novel autoantigens in murine lupus.Arthritis Rheum2004; 50: 3239–3249.
28.
28 Zhuang H Narain S Sobel E . Association of anti-nucleoprotein autoantibodies with upregulation of Type I interferon-inducible gene transcripts and dendritic cell maturation in systemic lupus erythematosus.Clin Immunol2005; 117: 238–250.
29.
29 Isenberg DA Rahman A Allen E . BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group's disease activity index for patients with systemic lupus erythematosus.Rheumatology (Oxford)2005; 44: 902–906.
30.
30 Yee CS Farewell V Isenberg DA . British isles lupus assessment group 2004 index is valid for assessment of disease activity in systemic lupus erythematosus.Arthritis Rheum2007; 56: 4113–4119.
31.
31 Hay EM Bacon PA Gordon C . The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus.Q J Med1993; 86: 447–458.
32.
32 Kosugi A Saitoh S Noda S . Physical and functional association between thymic shared antigen-1/stem cell antigen-2 and the T cell receptor complex.J Biol Chem1998; 273: 12301–12306.
33.
33 Pflugh DL Maher SE Bothwell AL . Ly-6 superfamily members Ly-6A/E, Ly-6C,and Ly-6I recognize two potential ligands expressed by B lymphocytes.J Immunol2002; 169: 5130–5136.
34.
34 Kumar KR Zhu J Bhaskarabhatla M Yan M Mohan C . Enhanced expression of stem cell antigen-1 (Ly-6A/E)in lymphocytes from lupus prone mice correlates with disease severity.J Autoimmun2005; 25: 215–222.
35.
35 Nakajima H Takenaka M Kaimori JY . Gene expression profile of renal proximal tubules regulated by proteinuria.Kidney Int2002; 61: 1577–1587.
36.
36 Ronnblom L Alm GV . A pivotal role for the natural interferon-α-producing cells (plasmacytoid dendritic cells)in the pathogenesis of lupus.J Exp Med2001; 194: F59–F63.
37.
37 Bave U Magnusson M Eloranta ML Perers A Alm GV Ronnblom L . FcγRIIa is expressed on natural IFN-α-producing cells (plasmacytoid dendritic cells)and is required for the IFN-α production induced by apoptotic cells combined with lupus IgG.J Immunol2003; 171: 3296–3302.
38.
38 Lovgren T Eloranta ML Bave U Alm GV Ronnblom L . Induction of interferon-α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG.Arthritis Rheum2004; 50: 1861–1872.
