Adenosine deaminase (ADA) has been found to be involved in autoimmune disease progression. To assess the potential application of serum ADA activity in diagnosing systemic lupus erythematosus (SLE) and evaluating SLE disease activity, we investigated the serum ADA activity of 120 SLE patients and 120 healthy controls in the present study. The results showed that serum ADA activity in SLE patients was significantly increased (median (IQR) = 14 (11–19) U/L) compared with that in healthy controls (median (IQR) = 8 (7–10) U/L). Based on a receiver operating characteristic curve analysis, the optimal cut-off value for using serum ADA activity to diagnose SLE patients was 10.5 U/L (specificity, 84.2%; sensitivity, 78.3%). The diagnostic performance of serum ADA activity for SLE patients was better than that of other conventional haematology markers. Moreover, serum ADA activity displayed an increasing trend with increasing SLE disease activity. Spearman’s correlation analysis showed that serum ADA activity was positively correlated with SLE disease activity. These findings suggest that serum ADA activity could be a diagnostic marker for SLE; moreover, measuring serum ADA activity may be helpful for evaluating and monitoring the disease activity of SLE patients.
This is a preview of subscription content,to check access.
Access this article
Similar content being viewed by others
Hasko G, Cronstein BN. Adenosine: an endogenous regulator of innate immunity. Trends Immunol. 2004;25(1):33–9. https://doi.org/10.1016/j.it.2003.11.003.
Hasko G, Linden J, Cronstein B, Pacher P. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov. 2008;7(9):759–70. https://doi.org/10.1038/nrd2638.
Franco R, Valenzuela A, Lluis C, Blanco J. Enzymatic and extraenzymatic role of ecto-adenosine deaminase in lymphocytes. Immunol Rev. 1998;161(1):27–42. https://doi.org/10.1111/j.1600-065X.1998.tb01569.x.
Whitmore KV, Gaspar HB. Adenosine deaminase deficiency—more than just an immunodeficiency. Front Immunol. 2016;7:314. https://doi.org/10.3389/fimmu.2016.00314.
Kwan A, Abraham RS, Currier R, Brower A, Andruszewski K, Abbott JK, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014;312(7):729–38. https://doi.org/10.1001/jama.2014.9132.
Cicalese MP, Ferrua F, Castagnaro L, Pajno R, Barzaghi F, Giannelli S, et al. Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency. 2016;128(1):45–54. https://doi.org/10.1182/blood-2016-01-688226.
Ferrua F, Brigida I, Aiuti A. Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency. Blood. 2010;10(6):551–6. https://doi.org/10.1182/blood-2016-01-688226.
Sauer AV, Morbach H, Brigida I, Ng YS, Aiuti A, Meffre E. Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy. J Clin Investig. 2012a;122(6):2141–52. https://doi.org/10.1172/jci61788.
Sauer AV, Brigida I, Carriglio N, Hernandez RJ, Scaramuzza S, Clavenna D, et al. Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID. Blood. 2012b;119(6):1428–39. https://doi.org/10.1182/blood-2011-07-366781.
Sauer AV, Brigida I, Carriglio N, Aiuti A. Autoimmune dysregulation and purine metabolism in adenosine deaminase deficiency. Front Immunol. 2012c;3:265. https://doi.org/10.3389/fimmu.2012.00265.
Vinapamula KS, Pemmaraju SV, Bhattaram SK, Bitla AR, Manohar SM. Serum adenosine deaminase as inflammatory marker in rheumatoid arthritis. J Clin Diagn Res: JCDR. 2015;9(9):Bc08–10. https://doi.org/10.7860/jcdr/2015/14296.6483.
Xun C, Zhao Y, Hu ZJ. Potential role of adenosine deaminase in the diagnosis of adult-onset Still’s disease. Rheumatol Int. 2013;33(5):1255–8. https://doi.org/10.1007/s00296-012-2532-z.
Taysi S, Polat MF, Sari RA, Bakan E. Serum adenosine deaminase and cytidine deaminase activities in patients with systemic lupus erythematosus. Clin Chem Lab Med. 2002;40(5):493–5. https://doi.org/10.1515/cclm.2002.085.
Nalesnik M, Nikolic JM, Jandric S. Adenosine deaminase and C-reactive protein in diagnosing and monitoring of rheumatoid arthritis. Medicinski Glasnik: Off Publ Med Assoc Zenica-Doboj Canton, Bosnia and Herzegovina. 2011;8(1):163–8.
Saghiri R, Ghashghai N, Movaseghi S, Poursharifi P, Jalilfar S, Bidhendi MA, et al. Serum adenosine deaminase activity in patients with systemic lupus erythematosus: a study based on ADA1 and ADA2 isoenzymes pattern. Rheumatol Int. 2012;32(6):1633–8. https://doi.org/10.1007/s00296-011-1836-8.
Hitoglou S, Hatzistilianou M, Gougoustamou D, Athanassiadou F, Kotsis A, Catriu D. Adenosine deaminase activity and its isoenzyme pattern in patients with juvenile rheumatoid arthritis and systemic lupus erythematosus. Clin Rheumatol. 2001;20(6):411–6.
Demir G, Borman P, Ayhan F, Ozgun T, Kaygisiz F, Yilmez G. Serum adenosine deaminase level is high but not related with disease activity parameters in patients with rheumatoid arthritis. Open Rheumatol J. 2014;8(1):24–8. https://doi.org/10.2174/1874312901408010024.
Zamani B, Jamali R, Jamali A. Serum adenosine deaminase may predict disease activity in rheumatoid arthritis. Rheumatol Int. 2012;32(7):1967–75. https://doi.org/10.1007/s00296-011-1912-0.
Wang D, Huang S, Yuan X, Liang J, Xu R, Yao G, et al. The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus. Cell Mol Immunol. 2015;14(5):423–31. https://doi.org/10.1038/cmi.2015.89.
Ohl K, Tenbrock K. Regulatory T cells in systemic lupus erythematosus. Eur J Immunol. 2015;45(2):344–55. https://doi.org/10.1002/eji.201344280.
Mak A, Kow NY. Imbalance between endothelial damage and repair: a gateway to cardiovascular disease in systemic lupus erythematosus. Biomed Res Int. 2014;2014:178721–11. https://doi.org/10.1155/2014/178721.
van den Berg L, Nossent H, Rekvig O. Prior anti-dsDNA antibody status does not predict later disease manifestations in systemic lupus erythematosus. Clin Rheumatol. 2006;25(3):347–52. https://doi.org/10.1007/s10067-005-0047-7.
Chung L, Flyckt RL, Colon I, Shah AA, Druzin M, Chakravarty EF. Outcome of pregnancies complicated by systemic sclerosis and mixed connective tissue disease. Lupus. 2006;15(9):595–9. https://doi.org/10.1177/0961203306071915.
Forger F, Matthias T, Oppermann M, Becker H, Helmke K. Clinical significance of anti-dsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis. Lupus. 2004;13(1):36–44. https://doi.org/10.1191/0961203304lu485oa.
Jolly M, Smaron M, Olsen Utset T, Ellman M. Are isolated antinucleolar antibodies a marker of scleroderma? J Clin Rheumatol: Pract Rep Rheumatic Musculoskelet Dis. 2003;9(5):291–5. https://doi.org/10.1097/01.rhu.0000089790.80026.f4.
van Venrooij WJ, Charles P, Maini RN. The consensus workshops for the detection of autoantibodies to intracellular antigens in rheumatic diseases. J Immunol Methods. 1991;140(2):181–9. https://doi.org/10.1016/0022-1759(91)90369-Q.
This study was supported by the National Natural Science Foundation of China (no. 81572974).
This project was approved by the Ethics Committee of the Tangdu Hospital, Fourth Military Medical University. Ethical approval was obtained from the Ethics Committee of Tangdu Hospital, Fourth Military Medical University (TDLL-20151209), and informed consent was not required.
Conflict of interests
The authors declare that they have no conflict of interest.
Electronic supplementary material
About this article
Cite this article
Gao, Zw., Zhao, Gh., Zhang, Z. et al. Serum adenosine deaminase activity is increased in systemic lupus erythematosus patients and correlated with disease activity. Immunol Res 66, 299–304 (2018). https://doi.org/10.1007/s12026-018-8984-9