Aktuelle Rheumatologie 2020; 45(04): 348-355
DOI: 10.1055/a-1024-3495
Original Article

Activities of Serum Adenosine Deaminase and its Isoenzymes in Patients with Systemic Lupus Erythematosus, Rheumatoid Arthritis, Ankylosing Spondylitis and Myasthenia Gravis

Die Aktivitäten der Adenosin-Desaminase im Serum sowie deren Isoenzyme bei Patienten mit systemischem Lupus erythematodes, rheumatoider Arthritis, Spondylitis ankylosans und Myasthenia gravis
Gao Zhao-wei
1   Fourth Military Medical University, Department of Clinical Diagnosis, Tangdu Hospital, Xi'an, China
,
Guan-hua Zhao
1   Fourth Military Medical University, Department of Clinical Diagnosis, Tangdu Hospital, Xi'an, China
,
Rui-cheng Li
1   Fourth Military Medical University, Department of Clinical Diagnosis, Tangdu Hospital, Xi'an, China
,
Hui-ping Wang
1   Fourth Military Medical University, Department of Clinical Diagnosis, Tangdu Hospital, Xi'an, China
,
Chong Liu
1   Fourth Military Medical University, Department of Clinical Diagnosis, Tangdu Hospital, Xi'an, China
,
Hui-zhong Zhang
1   Fourth Military Medical University, Department of Clinical Diagnosis, Tangdu Hospital, Xi'an, China
,
Ke Dong
1   Fourth Military Medical University, Department of Clinical Diagnosis, Tangdu Hospital, Xi'an, China
› Author Affiliations

Abstract

Objective The aim of this study was to evaluate the changes and diagnostic value of serum ADA activity in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), and myasthenia gravis (MG).

Methods Serum ADA activity, including total ADA (tADA) and its isoenzymes (ADA1 and ADA2), was determined in patients with different autoimmune diseases (144 RA, 114 SLE, 55 AS, 68 MG). The changes in serum ADA activity in patients were analysed. A receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of serum ADA activity.

Results Compared with healthy controls, the serum tADA activity in SLE patients was significantly increased (p<0.001), while the serum tADA activity in patients with RA, AS and MG did not change (p>0.05). The ROC analysis showed that the optimal cut-off value of serum tADA activity for SLE diagnosis was 10.5 U/L (79.8% specificity and 74.6% sensitivity; likelihood ratio (LR): 3.693; p<0.001). Moreover, our results showed that there were no significant changes of ADA1 and ADA2 activity in RA, AS and MG patients, while the serum ADA2 activity was significantly increased in SLE patients. The ROC analysis showed that ADA2 activity could be used in diagnosing SLE with 75.4% specificity and 78.1% sensitivity (LR: 3.175). Based on the ROC curve analysis, serum tADA activity (79.8% specificity and 74.6% sensitivity; likelihood ratio (LR): 3.693) and ADA2 activity (75.4% specificity and 78.1% sensitivity; LR: 3.175) are unlikely to be used in diagnosing SLE. Furthermore, there was a positive correlation between tADA activity and SLE disease activity (r=0.303, p=0.010). Notably, serum tADA activity in SLE patients with arthritis was higher than in patients without arthritis (p=0.005), which suggests that tADA activity might be related to lupus arthritis.

Conclusion These findings suggest that serum tADA and ADA2 activity might play an important role in SLE progression.

Zusammenfassung

Ziel Ziel dieser Studie war es, die Veränderungen sowie den diagnostischen Wert der ADA-Aktivität im Serum bei Autoimmunerkrankungen, einschließlich des systemischen Lupus erythematodes (SLE), der rheumatoiden Arthritis (RA), der Spondylitis ankylosans (AS) sowie der Myasthenia gravis (MG) zu beurteilen.

Methoden Die ADA-Aktivitäten im Serum, einschließlich Gesamt-ADA (tADA) sowie ihrer Isoenzyme (ADA1 und ADA2) wurden bei Patienten mit verschiedenen Autoimmunerkrankungen (144 RA, 114 SLE, 55 AS, 68 MG) bestimmt. Die Veränderungen der ADA-Aktivität im Serum bei den Patienten wurden analysiert. Die Grenzwertoptimierungskurve (ROC) wurde verwendet, um die Diagnostikleistung der ADA-Aktivitäten im Serum zu beurteilen.

Ergebnisse Im Vergleich zu den gesunden Kontrollen war die tADA-Aktivität im Serum bei den SLE-Patienten deutlich erhöht (P<0,001), während die tADA-Aktivität im Serum bei den Patienten mit RA, AS und MG unverändert blieb (P>0,05). Darüber hinaus wurden in unseren Ergebnissen gezeigt, dass es keine signifikanten Veränderungen bei den ADA1- und ADA2-Aktivitäten der RA-, AS- und MG-Patienten gaben, während die ADA2-Aktivität im Serum bei den SLE-Patienten deutlich erhöht wurde. Die ROC-Analyse zeigte, tADA-Aktivität (mit 79,8% iger Spezifität und 74,6%iger Sensitivität; LR: 3.693) und ADA2-Aktivität (mit 75,4% iger Spezifität und 78,1%iger Sensitivität; LR: 3.175) sind unwahrscheinlich bei der diagnose SLE. Außerdem gab es eine positive Korrelation zwischen tADA-Aktivität sowie SLE-Krankheitsaktivität (r=0,303, P=0,108). die Serum-tADA-Aktivität bei SLE-Patienten mit Arthritis höher war als bei Patienten ohne Arthritis (P=0.005)

Konklusion Diese Ergebnisse deuten darauf hin, dass die tADA- sowie ADA2-Aktivität im Serum eine wichtige Rolle bei der SLE-Progression spielen könnte



Publication History

Article published online:
21 November 2019

© Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 Antonioli L, Colucci R, La Motta C. et al. Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders. Current drug targets 2012; 13: 842-862
  • 2 Burnstock G, Boeynaems JM. Purinergic signalling and immune cells. Purinergic signalling 2014; 10: 529-564
  • 3 Ohta A, Sitkovsky M. Extracellular adenosine-mediated modulation of regulatory T cells. Frontiers in immunology 2014; 5: 304
  • 4 Flinn AM, Gennery AR. Adenosine deaminase deficiency: a review. Journal of animal physiology and animal nutrition 2018; 13: 65
  • 5 Bradford KL, Moretti FA, Carbonaro-Sarracino DA. et al. Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations. Journal of clinical immunology 2017; 37: 626-637
  • 6 Whitmore KV, Gaspar HB. Adenosine Deaminase Deficiency – More Than Just an Immunodeficiency. Frontiers in immunology 2016; 7: 314
  • 7 Blackburn MR, Aldrich M, Volmer JB. et al. The use of enzyme therapy to regulate the metabolic and phenotypic consequences of adenosine deaminase deficiency in mice. Differential impact on pulmonary and immunologic abnormalities. The Journal of biological chemistry 2000; 275: 32114-32121
  • 8 Blackburn MR, Kellems RE. Adenosine deaminase deficiency: metabolic basis of immune deficiency and pulmonary inflammation. Advances in immunology 2005; 86: 1-41
  • 9 Vinapamula KS, Pemmaraju SV, Bhattaram SK. et al. Serum Adenosine Deaminase as Inflammatory Marker in Rheumatoid Arthritis. Journal of clinical and diagnostic research : JCDR 2015; 9: Bc08 10
  • 10 Saghiri R, Ghashghai N, Movaseghi S. et al. Serum adenosine deaminase activity in patients with systemic lupus erythematosus: a study based on ADA1 and ADA2 isoenzymes pattern. Rheumatology international 2012; 32: 1633-1638
  • 11 Hitoglou S, Hatzistilianou M, Gougoustamou D. et al. Adenosine deaminase activity and its isoenzyme pattern in patients with juvenile rheumatoid arthritis and systemic lupus erythematosus. Clinical rheumatology 2001; 20: 411-416
  • 12 Nalesnik M, Nikolic JM, Jandric S. Adenosine deaminase and C-reactive protein in diagnosing and monitoring of rheumatoid arthritis. Medicinski glasnik: official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina 2011; 8: 163-168
  • 13 Demir G, Borman P, Ayhan F. et al. Serum Adenosine Deaminase Level is High But Not Related with Disease Activity Parameters in Patients with Rheumatoid Arthritis. The open rheumatology journal 2014; 8: 24-28
  • 14 Zamani B, Jamali R, Jamali A. Serum adenosine deaminase may predict disease activity in rheumatoid arthritis. Rheumatology international 2012; 32: 1967-1975
  • 15 Stancikova M, Lukac J, Istok R. et al. Serum adenosine deaminase activity and its isoenzyme pattern in patients with systemic lupus erythematosus. Clinical and experimental rheumatology 1998; 16: 583-586
  • 16 Cristalli G, Costanzi S, Lambertucci C. et al. Adenosine deaminase: functional implications and different classes of inhibitors. Medicinal research reviews 2001; 21: 105-128
  • 17 Sari RA, Taysi S, Yilmaz O. et al. Correlation of serum levels of adenosine deaminase activity and its isoenzymes with disease activity in rheumatoid arthritis. Clinical and experimental rheumatology 2003; 21: 87-90
  • 18 Chiba S, Saitoh M, Kashiwagi M. et al. Isozyme analysis of the high serum adenosine deaminase activity in patients with myasthenia gravis. Internal medicine (Tokyo, Japan) 1995; 34: 81-84
  • 19 Chiba S, Matsumoto H, Motoi Y. et al. High serum adenosine deaminase activity and its correlation with lymphocyte subsets in myasthenia gravis. Journal of the neurological sciences 1990; 100: 174-177
  • 20 Gao ZW, Zhao GH, Zhang Z. et al. Serum adenosine deaminase activity is increased in systemic lupus erythematosus patients and correlated with disease activity. Immunologic research 2018; 66: 299-304
  • 21 Mathian A, Mouries-Martin S, Dorgham K. Monitoring Disease Activity in Systemic Lupus Erythematosus With Single-Molecule Array Digital Enzyme-Linked Immunosorbent Assay Quantification of Serum Interferon-alpha. 2019; 71: 756-765
  • 22 Fernandez Matilla M, Grau Garcia E, Fernandez-Llanio Comella N. et al. Increased interferon-1alpha, interleukin-10 and BLyS concentrations as clinical activity biomarkers in systemic lupus erythematosus. Medicina clinica 2019; pii S0025-S7753 (19)30024-7
  • 23 Amoura Z, Chen JY, Wang CM. et al. Interferon-lambda3/4 genetic variants and interferon-lambda3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese. Arthritis & rheumatology 2018; 20: 193