Document Type : Original Article

Authors

1 Department of Rheumatology, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Community and Preventive Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Skin Disease and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Medical Students Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Objective: Recently, adenosine deaminase (ADA) is introduced as helpful marker in 
diagnosis, prognosis, and monitoring of treatment in rheumatoid arthritis (RA). The aim 
of this study was to determine the efficacy of the serum ADA in diagnosis, prognosis, and 
monitoring of treatment with methotrexate (MTX) in RA.
Methods: This was a self‑controlled clinical trial conducted in university hospitals of 
Isfahan, Iran. The serum level of ADA, erythrocyte sedimentation rate (ESR), and rheumatoid 
factor(RF) were measured for 70 patients with active RA (Disease Activity Score-28 [DAS28] 
> 3/2). After three months of MTX treatment and disease remission (DAS28 < 2.6) these 
markers were measured again. ANCOVA multiregression and paired t‑test were used to 
compare and evaluate the mean level and correlation of ADA, ESR, IgM‑RF, and DAS before 
and after RA remission.
Findings: The mean value for ADA activity was significantly higher than the normal one 
compared with other studies. Significant decreases were seen in values of ADA, ESR, 
RF, visual analogue scale (VAS), and DAS after remission. Also, the correlation coefficient 
between the values of ADA with ESR and DAS were statistically significant in baseline. 
Moreover, the statistically significant correlation between ADA and ESR, VAS, and DAS 
were seen after remission. No correlation was found in the case of the dosage of MTX 
with the value of ADA.
Conclusion: It was concluded that ADA may be considered useful as a marker in diagnosis, 
prognosis, and monitoring of treatment with Methotrexate in RA.

Keywords

1. Samanta R, Shoukrey K, Griffiths R. Rheumatoid arthritis and 
anaesthesia. Anaesthesia 2011;66:1146‑59.
2. McInnes IB, Schett G. The pathogenesis of rheumatoid 
arthritis. N Engl J Med 2011;365:2205‑19.
3. Nalesnik M, Nikolic JM, Jandric S. Adenosine deaminase 
and C‑reactive protein in diagnosing and monitoring of 
rheumatoid arthritis. Med Glas Ljek Komore Zenicko‑Doboj 
Kantona 2011;8:163‑8.
4. Goronzy JJ, Matteson EL, Fulbright JW, Warrington KJ, 
Chang‑Miller A, Hunder GG, et al. Prognostic markers of 
radiographic progression in early rheumatoid arthritis. 
Arthritis Rheum 2004;50:43‑54.
5. Yazici Y, Abramson SB. Rheumatoid arthritis treatment and 
monitoring of outcomes-where are we [corrected] in 2007? 
Bull NYU Hosp Jt Dis 2007;65:300‑5.
6. Aletaha D, Nell VP, Stamm T, Uffmann M, Pflugbeil S, 
Machold K, et al. Acute phase reactants add little to composite 
disease activity indices for rheumatoid arthritis: Validation of 
a clinical activity score. Arthritis Res Ther 2005;7:R796‑806.
7. Karsdal MA, Woodworth T, Henriksen K, Maksymowych WP, 
Genant H, Vergnaud P, et al. Biochemical markers of ongoing joint damage in rheumatoid arthritis-current and future 
applications, limitations and opportunities. Arthritis Res Ther 
2011;13:215.
8. Matsui T, Kuga Y, Kaneko A, Nishino J, Eto Y, Chiba N, et al. 
Disease activity score 28 (DAS28) using C‑reactive protein 
underestimates disease activity and overestimates EULAR 
response criteria compared with DAS28 using erythrocyte 
sedimentation rate in a large observational cohort of 
rheumatoid arthritis patients in Japan. Ann Rheum Dis 
2007;66:1221‑6.
9. 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;20:411‑6.
10. Sari RA, Taysi S, Yilmaz O, Bakan N. Correlation of serum 
levels of adenosine deaminase activity and its isoenzymes with 
disease activity in rheumatoid arthritis. Clin Exp Rheumatol 
2003;21:87‑90.
11. Cordero OJ, Salgado FJ, Mera‑Varela A, Nogueira M. Serum 
interleukin‑12, interleukin‑15, soluble CD26, and adenosine 
deaminase in patients with rheumatoid arthritis. Rheumatol 
Int 2001;21:69‑74.
12. UngererJP, Oosthuizen HM, Bissbort SH, Vermaak WJ. Serum 
adenosine deaminase: Isoenzymes and diagnostic application. 
Clin Chem 1992;38:1322‑6.
13. Agarwal MK, Nath J, Mukerji PK, Srivastava VM. A study 
of serum adenosine deaminase activity in sputum negative 
patients of pulmonary tuberculosis. Ind L Tub 1991;38:139‑41.
14. Nakamachi Y, Koshiba M, Nakazawa T, Hatachi S, Saura R, 
Kurosaka M, et al. Specific increase in enzymatic activity of 
adenosine deaminase 1 in rheumatoid synovial fibroblasts. 
Arthritis Rheum 2003;48:668‑74.
15. Surekha Rani H, Madhavi G, Srikanth BM, Jharna P, Rao UR, 
Jyothy A. Serum ADA and C‑reactive protein in rheumatoid 
arthritis. Int J Hum Genet 2006;6:195‑8.
16. Pallinti V, Ganesan N, Anbazhagan M, Rajasekhar G. Serum 
biochemical markers in rheumatoid arthritis. Indian J Biochem 
Biophys 2009;46:342-4.
17. Zamani B, Jamali R, Jamali A. Serum adenosine deaminase 
may predict disease activity in rheumatoid arthritis. 
Rheumatol Int 2012;32:1967‑75.
18. van Ede AE, Laan RF, De Abreu RA, Stegeman AB, van de 
Putte LB. Purine enzymes in patients with rheumatoid arthritis 
treated with methotrexate. Ann Rheum Dis 2002;61:1060‑4.
19. Montesinos MC, Takedachi M, Thompson LF, Wilder TF, 
Fernandez P, Cronstein BN. The antiinflammatory mechanism 
of methotrexate depends on extracellular conversion of 
adenine nucleotides to adenosine by ecto‑5′‑nucleotidase: 
Findings in a study of ecto‑5′‑nucleotidase gene‑deficient 
mice. Arthritis Rheum 2007;56:1440‑5.