Top

Journal of Clinical Immunology

Published in:

01-12-2012 | Original Research

Down-Regulation of A20 mRNA Expression in Peripheral Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus

Authors: Di Li, Lei Wang, Yuchen Fan, Lijun Song, Chun Guo, Faliang Zhu, Lining Zhang, Yongyu Shi

Published in: Journal of Clinical Immunology | Issue 6/2012

Abstract

Purpose

A20 gene functions in negative immunoregulation and its SNP is related to SLE disease. But its expression level in immune cells from SLE patients is still unclear. The aim of this study is to investigate whether the expression of A20 is associated with pathogenesis of SLE.

Methods

Real-time transcription-polymerase chain reaction analysis (RT-PCR) was used to determine expression of A20 mRNA in peripheral blood mononuclear cells (PBMC) from 37 patients with SLE and 32 healthy controls.

Results

A20 expression was decreased in SLE patients compared with healthy controls (p = 0.0133). The expression level of A20 gene negatively correlated with the SLE disease activity index (SLEDAI) (r =−0.4661, p = 0.0036) and erythrocyte sedimentation rate (ESR) (r =−0.5222, p = 0.0009). Furthermore, SLE patients with nephritis had a lower expression of A20 than those without nephritis (p = 0.0188).

Conclusions

Our results suggest that the insufficient expression of A20 gene in PBMC may take part in the pathogenesis of SLE disease.

Apostolidis SA, Lieberman LA, Kis-Toth K, et al. The dysregulation of cytokine networks in systemic lupus erythematosus. J Interferon Cytokine Res. 2011;31:769–79.PubMedCrossRef

Hrycek A, Kusmierz D, Dybała T, et al. Expression of messenger RNA for transforming growth factor-beta1 and for transforming growth factor-beta receptors in peripheral blood of systemic lupus erythematosus patients treated with low doses of quinagolide. Autoimmunity. 2007;40:23–30.PubMedCrossRef

Wong CK, Lit LC, Tam LS, et al. Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2005;44:989–94.CrossRef

Fujimoto M, Tsutsui H, Xinshou O, et al. Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases. Int Immunol. 2004;16:303–14.PubMedCrossRef

Zhang B, Zhang X, Tang F, et al. Reduction of forkhead box P3 levels in CD4 + CD25high T cells in patients with new-onset systemic lupus erythematosus. Clin Exp Immunol. 2008;153:182–7.PubMedCrossRef

Vereecke L, Beyaert R, van Loo G. The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol. 2009;30:383–91.PubMedCrossRef

Coornaert B, Carpentier I, Beyaert R. A20: central gatekeeper in inflammation and immunity. J Biol Chem. 2009;284:8217–21.PubMedCrossRef

Kingeter LM, Paul S, Maynard SK, et al. Cutting edge: TCR ligation triggers digital activation of NF-kappaB. J Immunol. 2010;185:4520–4.PubMedCrossRef

Düwel M, Welteke V, Oeckinghaus A, et al. A20 negatively regulates T cell receptor signaling to NF-kappaB by cleaving Malt1 ubiquitin chains. J Immunol. 2009;182:7718–28.PubMedCrossRef

10.

Verstrepen L, Verhelst K, van Loo G, et al. Expression, biological activities and mechanisms of action of A20 (TNFAIP3). Biochem Pharmacol. 2010;80:2009–20.PubMedCrossRef

11.

Vereecke L, Beyaert R, van Loo G. Genetic relationships between A20/TNFAIP3, chronic inflammation and autoimmune disease. Biochem Soc Trans. 2011;39:1086–91.PubMedCrossRef

12.

Hövelmeyer N, Reissig S, Xuan NT, et al. A20 deficiency in B cells enhances B-cell proliferation and results in the development of autoantibodies. Eur J Immunol. 2011;41:595–601.PubMedCrossRef

13.

Ohl K, Tenbrock K. Inflammatory cytokines in systemic lupus erythematosus. J Biomed Biotechnol. 2011;2011:432595.PubMedCrossRef

14.

Matmati M, Jacques P, Maelfait J, et al. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nat Genet. 2011;43:908–12.PubMedCrossRef

15.

Bombardier C, Gladman DD, Hurwitz MB, et al. Derivation of the SLEDAI: a disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum. 1992;35:630–40.PubMedCrossRef

16.

Hawker G, Gabriel S, Bombardier C, et al. A reliability study of SLEDAI: a disease activity index for systemic lupus erythematosus. J Rheumatol. 1993;20:657–60.PubMed

17.

Boonyasrisawat W, Eberle D, Bacci S, et al. Tag polymorphisms at the A20 (TNFAIP3) locus are associated with lower gene expression and increased risk of coronary artery disease in type 2 diabetes. Diabetes. 2007;56:499–505.PubMedCrossRef

18.

Adrianto I, Wen F, Templeton A, et al. Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus. Nat Genet. 2011;43:253–8.PubMedCrossRef

19.

Frenzel LP, Claus R, Plume N, et al. Sustained NF-kappaB activity in chronic lymphocytic leukemia is independent of genetic and epigenetic alterations in the TNFAIP3 (A20) locus. Int J Cancer. 2011;128:2495–500.PubMedCrossRef

20.

Chanudet E, Huang Y, Ichimura K, et al. A20 is targeted by promoter methylation, deletion and inactivating mutation in MALT lymphoma. Leukemia. 2010;24:483–7.PubMedCrossRef

21.

Graham RR, Cotsapas C, Davies L, et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet. 2008;40:1059–61.PubMedCrossRef

22.

Musone SL, Taylor KE, Lu TT, et al. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet. 2008;40:1062–4.PubMedCrossRef

23.

Tavares RM, Turer EE, Liu CL, et al. The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity. Immunity. 2010;33:181–91.PubMedCrossRef

24.

Kool M, van Loo G, Waelput W, et al. The ubiquitin-editing protein A20 prevents dendritic cell activation, recognition of apoptotic cells, and systemic autoimmunity. Immunity. 2011;35:82–96.PubMedCrossRef

Title: Down-Regulation of A20 mRNA Expression in Peripheral Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus
Authors: Di Li
Lei Wang
Yuchen Fan
Lijun Song
Chun Guo
Faliang Zhu
Lining Zhang
Yongyu Shi
Publication date: 01-12-2012
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 6/2012
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-012-9764-2

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2012

Elevated Serum Osteopontin Levels in Chronic Hepatitis C Virus Infection: Association with Autoimmune Rheumatologic Manifestations

D-chiro-inositol Negatively Regulates the Formation of Multinucleated Osteoclasts by Down-Regulating NFATc1

2012 CIS Annual Meeting: Primary Immune Deficiency Diseases North American Conference

The Lupus-derived Anti-double-stranded DNA IgG Contributes to Myofibroblast-like Phenotype in Mesangial Cells

Efficacy Assessments in Randomized Controlled Studies of Acute Therapy for Hereditary Angioedema

Three Different Classifications, B Lymphocyte Subpopulations, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF13 (APRIL) Gene Mutations, CTLA-4 and ICOS Gene Polymorphisms in Turkish Patients with Common Variable Immunodeficiency

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials