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Serum activities of adenosine deaminase, dipeptidyl peptidase IV and prolyl endopeptidase in patients with fibromyalgia: diagnostic implications

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Abstract

Fibromyalgia (FM) is a chronic pain syndrome with number of symptoms that present challenge in terms of diagnosis and treatment. Patients with FM show abnormal profile of purines in plasma. In this work, we measured serum activities of enzymes involved in purine metabolism, namely total adenosine deaminase (ADE) and its isoforms (ADE1 and ADE2), ecto-ATPase, and 5′-nucleotidase (5′-NT). We also measured activity of dipeptidyl peptidase IV (DPPIV) and prolyl endopeptidase (PEP). Spectrophotometric and fluorometric methods were used for enzyme activity determinations. Enzyme activities were measured in sera of 24 patients with FM that were not undergoing pharmacological treatment during the study. Control group comprised 32 healthy control subjects. Significantly higher activities of total ADE (P = 0.025) and ADE2 (P = 0.011) were observed in FM patients, while no significant differences in ADE1, ecto-ATPase, and 5′-NT activities (P > 0.05) were found when compared to healthy controls. Moreover, increase in the activity of DPPIV (P = 0.015) and lower activity of PEP (P = 0.011) were also found in the FM group. ROC analysis pointed to different diagnostic sensitivities/specificities for individual enzyme activities measured as follows: ADE (50.0/87.5), ADE2 (41.7/90.6), DPPIV (62.5/71.9), and PEP (83.3/62.5). ADE2 and PEP were shown to be independent predictors of FM, while combination of the two gives AUC of 0.786 (95 % confidence interval of 0.656–0.885, P < 0.05). Our results are showing that serum activities of ADE2 and PEP could be useful as biomarkers for FM diagnosis. However, relatively low diagnostic sensitivity of ADE2 and specificity of PEP must be taken into account.

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References

  1. Wolfe F (2010) New American College of Rheumatology criteria for fibromyalgia: a twenty-year journey. Arthritis Care Res 62(5):583–584

    Article  Google Scholar 

  2. Wolfe F, Smythe HA, Yunus MB, Benett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, Fam AG, Farber SJ, Fiechtner JJ, Franklin CM, Gatter RA, Hamaty D, Lessard AS, Lichtbroun AT, Masi AM, Glenn A, McCain W, Reynolds J, RomanoTJ RJ, Sheon RP (1990) The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis Rheum 33:160–172

    Article  CAS  PubMed  Google Scholar 

  3. Fais A, Cacace E, Corda M, Era B, Peri M, Utzeri S, Ruggiero V (2013) Purine metabolites in fibromyalgia syndrome. Clin Biochem 46(1–2):37–39

    Article  CAS  PubMed  Google Scholar 

  4. Zylka MJ (2011) Pain-relieving prospects for adenosine receptors and ectonucleotidases. Trends Mol Med 17(4):188–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sawynok J, Liu XJ (2003) Adenosine in the spinal cord and periphery: release and regulation of pain. Prog Neurobiol 69:313–340

    Article  CAS  PubMed  Google Scholar 

  6. Huang ZL, Zhang Z, Qu WM (2014) Roles of adenosine and its receptors in sleep-wake regulation. Int Rev Neurobiol 119:349–371

    Article  PubMed  Google Scholar 

  7. Guieu R, Guedj E, Giorgi R, Dousset A, Tuzzolino V, By Y, Leveque JM, Peragut JC, Régis J, Ruf J, Fenouillet E, Roussel P (2012) High cell surface CD26-associated activities and low plasma adenosine concentration in fibromyalgia. Ann Rheum Dis 71(8):1427–1428

    Article  CAS  PubMed  Google Scholar 

  8. Maes M, Libbrecht I, Van Hunsel F, Lin AH, Bonaccorso S, Goossens F, De Meester I, De Clerck L, Biondi M, Scharpe S, Janca A (1998) Lower serum activity of prolyl endopeptidase in fibromyalgia is related to severity of depressive symptoms and pressure hyperalgesia. Psychol Med 28(4):957–965

    Article  CAS  PubMed  Google Scholar 

  9. Kreisel W, Heussner R, Volk B, Buchsel R, Reutter W, Gerok W (1982) Identification of the 110000 Mr glycoprotein isolated from rat liver plasma membrane as dipeptidylaminopeptidase IV. FEBS Lett 147(1):85–88

    Article  CAS  PubMed  Google Scholar 

  10. Larrinaga G, Perez I, Blanco L, Sanz B, Errarte P, Beitia M, Etxezarraga MC, Loizate A, Gil J, Irazusta J, López JI (2014) Prolyl endopeptidase activity is correlated with colorectal cancer prognosis. Int J Med Sci 11(2):199–208

    Article  PubMed  PubMed Central  Google Scholar 

  11. Culic O, Sabolic I, Zanic-Grubisic T (1990) The stepwise hydrolysis of adenine nucleotides by ectoenzymes of rat renal brush-border membranes. Biochim Biophys Acta 1030(1):143–151

    Article  CAS  PubMed  Google Scholar 

  12. Fiske CH, Subbarow Y (1925) The colorimetric determination of phosphorous. J Biol Chem 66:375–400

    CAS  Google Scholar 

  13. Yu DM, Yao TW, Chowdhury S, Nadvi NA, Osborne B, Church WB, McCaughan GW, Gorrell MD (2010) The dipeptidyl peptidase IV family in cancer and cell biology. FEBS J 277(5):1126–1144

    Article  CAS  PubMed  Google Scholar 

  14. Mendieta D, De la Cruz-Aquilera DL, Barrera-Villalpando MI, Becerril-Villanueva E, Arreola R, Hernandez-Ferreira E, Perez-Tapia SM, Perez-Sanchez G, Garces-Alvaraez ME, Aquirre-Cruz L, Velasco-Velazquez MA, Pavon T (2016) Il-8 and IL-6 primarily mediate the inflammatory response in fibromyalgia patients. J Neuroimmunol 290:22–25

    Article  CAS  PubMed  Google Scholar 

  15. Ruggiero V, Cacace E, Era B, Fais A (2016) J Musculoskelet Pain (early online 1–2)

  16. Buljevic S, Detel D, Pucar LB, Mihelic R, Madarevic T, Sestan B, Varljen J (2013) Levels of dipeptidyl peptidase IV/CD26 substrates neuropeptide Y and vasoactive intestinal peptide in rheumatoid arthritis patients. Rheumatol Int 33(11):2867–2874

    Article  CAS  PubMed  Google Scholar 

  17. Castro-Marrero J, Cordero MD, Sáez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J (2013) Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal 19(15):1855–1860

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Larrinaga’s group, especially Dr. Maider Betia for the valuable help in the establishment of PEP activity determination method.

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Authors and Affiliations

  1. Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000, Zagreb, Croatia

    Ognjen Čulić

  2. IBiS Institute of Biomedicine of Seville, University Hospital Virgen del Rocío-CSIC-University of Seville, Seville, Spain

    Mario D. Cordero

  3. Department of Medical Biochemistry and Hematology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Kneza Domagoja 2, 10000, Zagreb, Croatia

    Tihana Žanić-Grubišić, Anita Somborac-Bačura & Karmela Barišić

  4. Department of Chemistry and Biochemistry, University of Rijeka, School of Medicine, Braće Branchetta 20, 51000, Rijeka, Croatia

    Lara Batičić Pučar, Dijana Detel & Jadranka Varljen

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  1. Ognjen Čulić
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  2. Mario D. Cordero
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  3. Tihana Žanić-Grubišić
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  5. Lara Batičić Pučar
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  6. Dijana Detel
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  7. Jadranka Varljen
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  8. Karmela Barišić
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Correspondence to Ognjen Čulić.

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The approval of the Ethical Committee was obtained, according to the principles of the Declaration of Helsinki and all the International Conferences on Harmonization and Good Clinical Practice Guidelines. All the participants involved in the study gave their written informed consent before initiating the study.

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Čulić, O., Cordero, M.D., Žanić-Grubišić, T. et al. Serum activities of adenosine deaminase, dipeptidyl peptidase IV and prolyl endopeptidase in patients with fibromyalgia: diagnostic implications. Clin Rheumatol 35, 2565–2571 (2016). https://doi.org/10.1007/s10067-016-3377-8

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  • DOI: https://doi.org/10.1007/s10067-016-3377-8

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