Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Research
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. 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.

    Article  PubMed  CAS  Google Scholar 

  2. 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.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

    Article  CAS  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Nature Science Foundation of China (No. 81071705 and No. 30500591), the Award Funds for Excellent Young and Middle-aged Scientists of Shandong Province (BS2009YY002) and the National “973” Program of China (No. 2011CB503906).

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Institute of Immunology, School of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan, 250012, China

    Di Li, Chun Guo, Faliang Zhu, Lining Zhang & Yongyu Shi

  2. Campus Hospital, Shandong University, Jinan, China

    Lei Wang

  3. Department of Rheumatology, Qilu Hospital of Shandong University, Jinan, China

    Lijun Song

  4. Clinical Laboratory, Qingdao Municipal Hospital, Qingdao, 266071, China

    Di Li

  5. Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China

    Yuchen Fan

Authors
  1. Di Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuchen Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lijun Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chun Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Faliang Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lining Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yongyu Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yongyu Shi.

Additional information

Di Li and Lei Wang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, D., Wang, L., Fan, Y. et al. Down-Regulation of A20 mRNA Expression in Peripheral Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus. J Clin Immunol 32, 1287–1291 (2012). https://doi.org/10.1007/s10875-012-9764-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-012-9764-2

Keywords

Search

Navigation