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Current Rheumatology Reviews


ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Research Article

Adenosine Deaminase Activity and HLA-DRB as Diagnostic Markers for Rheumatoid Arthritis

Author(s): Shirin Valadbeigi, Reza Saghiri*, Mina Ebrahimi-Rad, Shohreh Khatami and Hadi Akhbari

Volume 15 , Issue 1 , 2019

Page: [44 - 49] Pages: 6

DOI: 10.2174/1573397114666180406101239

Price: $65


Background: Rheumatoid Arthritis (RA) is a chronic multi systemic disorder with the unclarified ethiopathology. Although several markers have been presented for recognition of RA, but none of them has been specific. New markers such as HLA typing and activity of Adenosine Deaminase (ADA) isoenzymes could be useful and specific.

Objective: The aim of this study is to evaluate the pattern of ADA isoenzymes activity and HLA typing in both RA patients and healthy cases.

Methods: Blood samples were collected from 55 RA patients and 60 healthy subjects, over a period of 6 months. Levels of C-reactive Protein (CRP), Rheumatoid Factor (RF) and ADA (ADA1, ADA2, total ADA) were measured using AVITEX kit and HITACHI Auto Analyzer. In addition, HLA-DRB1*01,*04 and *10 was detected using PCR-SSP.

Results: ADA activity, particularly ADA2 level, was significantly higher among RA group (Pv <0.05). The concentrations of tADA in patients with RF and CRP positive were significantly higher (Pv <0.05). The allele prevalence of DRB1*01 was significantly higher in RA patients (13.1%) compared with control group (5.5%, respectively) (P <0.05, Bonferroni adjustment P<0.003). Calculated sensitivity and specificity for diagnostic tests in this study are listed as: CRP (75%), RF (80%), ADA (84%) and RF (90%), ADA (83%), CRP (72%), respectively.

Conclusion: Increased tADA level and the frequency of DRB1*10 and *01 caused susceptibility to RA.

Keywords: Adenosine deaminase, rheumatoid arthritis, rheumatoid factor, c-reactive protein, HLA typing, HLA-DRB.

Graphical Abstract
Zakeri Z, Izadi S, Niazi A, et al. Comparison of adenosine deaminase levels in serum and synovial fluid between patients with rheumatoid arthritis and osteoarthritis. Int J Clin Exp Med 2012; 5(2): 195-200.
Mourad J, Monem F. HLA-DRB1 allele association with rheumatoid arthritis susceptibility and severity in Syria. Rev Bras Reumatol 2013; 53(1): 47-56.
Ungerer JP, Oosthuizen HM, Bissbort SH, Vermaak WJ. Serum adenosine deaminase: Isoenzymes and diagnostic application. Clin Chem 1992; 38(7): 1322-6.
Gessi S, Varani K, Merighi S, et al. Adenosine and lymphocyte regulation. Purinergic Signal 2007; 3(1-2): 109-16.
Rokayan SA. Serum adenosine deaminase activity and its isoenzyme in patients treated for tuberculosis. J Coll Physicians Surg Pak 2003; 13(1): 11-4.
Erer B, Yilmaz G, Yilmaz FM, Koklu S. Assessment of adenosine deaminase levels in rheumatoid arthritis patients receiving anti-TNF-alpha therapy. Rheumatol Int 2009; 29(6): 651-4.
Valdés L, San José E, Alvarez D, Valle JM. Adenosine deaminase (ADA) isoenzyme analysis in pleural effusions: Diagnostic role, and relevance to the origin of increased ADA in tuberculous pleurisy. Eur Respir J 1996; 9(4): 747-51.
Bax M, van Heemst J, Huizinga TW, Toes RE. Genetics of rheumatoid arthritis: What have we learned? Immunogenetics 2011; 63(8): 459-66.
Louthrenoo W, Kasitanon N, Wangkaew S, Kuwata S, Takeuchi F. Distribution of HLA-DR alleles among Thai patients with rheumatoid arthritis. Hum Immunol 2015; 76(2-3): 113-7.
Kochi Y, Suzuki A, Yamada R, Yamamoto K. Genetics of rheumatoid arthritis: Underlying evidence of ethnic differences. J Autoimmun 2009; 32(3-4): 158-62.
Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 1998; 101(1): 273-81.
Verheul MK, Fearon U, Trouw LA, Veale DJ. Biomarkers for rheumatoid and psoriatic arthritis. Clin Immunol 2015; 161(1): 2-10.
Nakamachi Y, Koshiba M, Nakazawa T, et al. Specific increase in enzymatic activity of adenosine deaminase 1 in rheumatoid synovial fibroblasts. Arthritis Rheum 2003; 48(3): 668-74.
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.
Ocaña I, Ribera E, Martinez-Vázquez JM, et al. Adenosine deaminase activity in rheumatoid pleural effusion. Ann Rheum Dis 1988; 47(5): 394-7.
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(1): 87-90.
Yuksel H, Akoğlu TF. Serum and synovial fluid adenosine deaminase activity in patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis. Ann Rheum Dis 1988; 47(6): 492-5.
Zamani B, Jamali R, Jamali A. Serum adenosine deaminase may predict disease activity in rheumatoid arthritis. Rheumatol Int 2012; 32(7): 1967-75.
Stancíková M, Rovenský J. Effect of cyclosporin on the activity of cytidine deaminase and adenosine deaminase in the serum and polymorphonuclear leukocytes of patients with rheumatoid arthritis. Int J Tissue React 1993; 15(4): 169-74.
Pallinti V, Ganesan N, Anbazhagan M, Rajasekhar G. Serum biochemical markers in rheumatoid arthritis. Indian J Biochem Biophys 2009; 46(4): 342-4.
Dhaouadi T, Sfar I, Abdelmoula L, et al. Association of specific amino acid sequence (QRRAA) of HLA-DRB1*0405 with rheumatoid arthritis in a Tunisian population. Arch Inst Pasteur Tunis 2010; 87(1-2): 53-9.
Uçar F, Karkucak M, Alemdaroğlu E, et al. HLA-DRB1 allele distribution and its relation to rheumatoid arthritis in eastern Black Sea Turkish population. Rheumatol Int 2012; 32(4): 1003-7.
Stark K, Rovenský J, Blazicková S, et al. Association of common polymorphisms in known susceptibility genes with rheumatoid arthritis in a Slovak population using osteoarthritis patients as controls. Arthritis Res Ther 2009; 11(3): R70.
Sandoughi M, Fazaeli A, Bardestani G, Hashemi M. Frequency of HLA-DRB1 alleles in rheumatoid arthritis patients in Zahedan, southeast Iran. Ann Saudi Med 2011; 31(2): 171-3.
Castro F, Acevedo E, Ciusani E, Angulo JA, Wollheim FA, Sandberg-Wollheim M. Tumour necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles in Peruvian patients with rheumatoid arthritis. Ann Rheum Dis 2001; 60(8): 791-5.
Balsa A, Minaur NJ, Pascual-Salcedo D, et al. Class II MHC antigens in early rheumatoid arthritis in Bath (UK) and Madrid (Spain). Rheumatology (Oxford) 2000; 39(8): 844-9.
Bongi SM, Porfirio B, Rombolà G, Palasciano A, Beneforti E, Bianucci G. Shared-epitope HLA-DRB1 alleles and sex ratio in Italian patients with rheumatoid arthritis. Joint Bone Spine 2004; 71(1): 24-8.
Laivoranta-Nyman S, Möttönen T, Hermann R, et al. HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis. Ann Rheum Dis 2004; 63(11): 1406-12.
Yukioka M, Wakitani S, Murata N, et al. Elderly-onset rheumatoid arthritis and its association with HLA-DRB1 alleles in Japanese. Br J Rheumatol 1998; 37(1): 98-101.
Louzada-Júnior P, Freitas MV, Oliveira RD, et al. A majority of Brazilian patients with rheumatoid arthritis HLA-DRB1 alleles carry both the HLA-DRB1 shared epitope and anti-citrunillated peptide antibodies. Braz J Med Biol Res 2008; 41(6): 493-9.
Al-Swailem R, Al-Rayes H, Sobki S, Arfin M, Tariq M. HLA-DRB1 association in Saudi rheumatoid arthritis patients. Rheumatol Int 2006; 26(11): 1019-24.
Liu SC, Chang TY, Lee YJ, et al. Influence of HLA-DRB1 genes and the shared epitope on genetic susceptibility to rheumatoid arthritis in Taiwanese. J Rheumatol 2007; 34(4): 674-80.

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