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Higher Serum DPP-4 Enzyme Activity and Decreased Lymphocyte CD26 Expression in Type 1 Diabetes

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Pathology & Oncology Research

Abstract

Dipeptidyl peptidase-4 (DPP-4) is involved in the metabolism of peptide hormones, T-cell activation and proliferation. In type 1 diabetes mellitus (T1DM) β-cell destruction involves a number of dysregulated T-cells. Our aim was to assess the serum DPP-4 activity and the lymphocyte membrane bound CD26 expression in patients with type 1 diabetes and healthy controls. Ninety-eight (T1DM: 48, F/M = 20/28, mean age: 34.4y; control: 50, F/M = 39/11 mean age: 32,4y) individuals were included. Fasting serum DPP-4 enzymatic activity, plasma glucose (FPG), CD26 expression on CD3+, CD4+ and CD8+ lymphocytes, HbA1c and body mass index (BMI) were assessed. ICA and GAD antibodies were assessed in the T1DM group. DPP-4 enzymatic activity was determined by kinetic enzyme assay, ICA and GAD were assessed by ELISA. Determination of the CD26 expression on CD3+, CD4+ and CD8+ lymphocytes was performed by flow-cytometric analysis. We found higher serum DPP-4 activity (Mean: T1DM: 30.069 U/L, control: 22.62 U/L, p < 0.0001) and decreased CD26 lymphocyte expression on all lymphocyte subpopulations in T1DM. Fasting serum DPP-4 activity was independent from the ICA or GAD status of patients with T1DM. Here we first present that the serum DPP-4 activity is increased and the lymphocyte membrane bound CD26 expression is decreased in type 1 diabetes. Decreased lymphocyte membrane bound CD26 expression in T1DM might be a novel part of the T-lymphocyte regulatory dysfunction observed in type 1 diabetes mellitus. These results might provide some basis for the clinical implication of DPP-4 inhibition in patients with T1DM.

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Abbreviations

DPP-4 CD26:

Dipeptidyl peptidase-4

ICA:

Islet cell antibody

GAD:

Glutamic acid decarboxylase antibody

GLP-1:

Glucagon like peptide-1

HbA1C:

Glycated haemoglobin

BMI:

Body mass index

FPG:

Fasting plasma glucose

References

  1. Gorrell MD, Gysbers V, McCaughan GW (2001) CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scand J Immunol 54:249–264

    Article  PubMed  CAS  Google Scholar 

  2. Morimoto C, Schlossman SF (1998) The structure and function of CD26 in the T-cell immune response. Immunol Rev 161:55–70

    Article  PubMed  CAS  Google Scholar 

  3. Ohnuma K, Yamochi T, Uchiyama M, Nishibashi K, Iwata S, Morimoto C (2005) CD26 mediates dissociation of Tollip and IRAK-1 from caveolin-1 and induces upregulation of CD86 on antigen-presenting cells. Mol Cell Biol 25:7743–7757

    Article  PubMed  CAS  Google Scholar 

  4. Ikushima H, Munakata Y, Iwata S, Ohnuma K, Kobayashi S, Morimoto C (2002) Soluble CD26/dipeptidyl peptidase IV enhances transendothelial migration via its interaction with mannose 6-phosphate/insulin-like growth factor II receptor. Cell Immunol 215:106–110

    Article  PubMed  CAS  Google Scholar 

  5. Ohnuma K, Takahashi N, Yamochi T, Hosono O, Dang NH, Morimoto C (2008) Role of CD26/dipeptidyl peptidase IV in human T cell activation and function. Front Biosci 13:2299–2310

    Article  PubMed  CAS  Google Scholar 

  6. Ohnuma K, Dang NH, Morimoto C (2008) Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends Immunol 29(6):295–301

    Article  PubMed  CAS  Google Scholar 

  7. Stone SF, Lee S, Keane NM, Price P, French MA (2002) Association of increased Hepatitis C Virus (HCV)–Specific IgG and soluble CD26 Dipeptidyl peptidase IV enzyme activity with hepatotoxicity after highly active antiretroviral therapy in human immunodeficiency virus–HCV-coinfected patients. J Infect Dis 186:1498–1502

    Article  PubMed  CAS  Google Scholar 

  8. Kobayashi H, Hosono U, Mimori T, Kawasaki H, Hoang Dang N, Tanaka H, Morimoto C (2000) Reduction of serum soluble CD26/dipeptidyl peptidase IV enzyme activity and its correlation with disease activity in systemic lupus erythematosus. J Rheumatol 29(9):1858–1866

    Google Scholar 

  9. Cordero OJ, Salgado FJ, Meravarela A, Nogueira M (2001) Serum interleukin-12, interleukin- 15, soluble CD26, and adenosine deaminase in patients with rheumatoid arthritis. Rheumatol Int 21:69–74

    Article  PubMed  CAS  Google Scholar 

  10. Schonermarck U, Csernok E, Trabandt A, Hansen H, Gross WL (2000) Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA associated vasculitides. Clin Exp Rheumatol 18:457–463

    PubMed  CAS  Google Scholar 

  11. Firneisz G, Lakatos PL, Szalay F, Hungarian Viral Hepatitis Study Group (2001) Serum dipeptidyl peptidase IV (DPP IV, CD26) activity in chronic hepatitis C. Scand J Gastroenterol 36:877–880

    Article  PubMed  CAS  Google Scholar 

  12. Lefebvre J, Murphey LJ, Hartert TV, Jiao Shan R, Simmons WH, Brown NJ (2002) Dipeptidyl peptidase IV activity in patients with ACE-inhibitor associated angioedema. Hypertension 39:460–464

    Article  PubMed  CAS  Google Scholar 

  13. Stancikova M, Lojda Z, Lukac J, Ruzickova M (1992) Dipeptidyl peptidase IV in patients with systemic lupus erythematosus. Clin Exp Rheumatol 10:381–385

    PubMed  CAS  Google Scholar 

  14. Blazquez MV, Madueno JA, Gonzalez R, Jurado R, Bachovchin WW, Pena J, Munoz E (1992) Selective decrease of CD26 expression in T cells from HIV-1-infected individuals. J Immunol 149(9):3073–3077

    PubMed  CAS  Google Scholar 

  15. Jones D, Dang NH, Duvic M, Washington LT, Huh YO (2001) Absence of CD26 expression is a useful marker for diagnosis of T-cell lymphoma in peripheral blood. Am J Clin Pathol 115(6):885–892

    Article  PubMed  CAS  Google Scholar 

  16. Firneisz G, Varga T, Lengyel G, Fehér J, Ghyczy D, Wichmann B, Selmeci L, Tulassay Zs, Rácz K, Somogyi A (2010) Serum dipeptidyl peptidase-4 activity in insulin resistant patients with non-alcoholic fatty liver disease: a novel liver disease biomarker. PLOS One 5(8):e12226

    Article  PubMed  Google Scholar 

  17. Varga T et al (2008) Higher serum dipeitidyl peptidase-4 activity in type 1 diabetes mellitus than in type 2: a direct comparison. Diabetologia 51(Suppl 1):S239, A589

    Google Scholar 

  18. Selmeci L, Szokodi I, Horvat-Karajz K (1996) A sensitive microplate-based continuous monitoring (kinetic) assay for serum neutral endopeptidase (EC 3.4.24.11) activity. Clin Chim Acta 244:111–116

    Article  PubMed  CAS  Google Scholar 

  19. Ellis SL, Moser EG, Snell-Bergeon JK, Gutin RS, Rodionova AS, Garg SK (2010) Effect of sitagliptin on glucose control in patients with type 1 diabetes- a pilot study. Diabetologia 53:S39, A77

    Google Scholar 

  20. Andrieu T, Thibault V, Malet I, Laporte J, Bauvois B, Agut H, Cahour A (2003) Similar increased serum dipeptidyl peptidase IV activity in chronic hepatitis C and other viral infections. J Clin Virol 27:59–68

    Article  PubMed  CAS  Google Scholar 

  21. Hadjiyanni I, Siminovitch KA, Danska JS, Drucker DJ (2010) Glucagon-like peptide-1 receptor signalling selectively regulates murine lymphocyte proliferation and maintenance of peripheral regulatory T cells. Diabetologia 53:730–740

    Article  PubMed  CAS  Google Scholar 

  22. Morran MP, Omenn GS, Pietropaolo M (2008) Immunology and genetics of type 1 diabetes. Mt Sinai J Med 75(4):314–327

    Article  PubMed  Google Scholar 

  23. Hafler DA, Fox DA, Manning ME, Schlossman SF, Reinherz EL, Weiner HL (1985) In vivo activated T lymphocytes in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. N Engl J Med 312:1405–1411

    Article  PubMed  CAS  Google Scholar 

  24. Ohnuma K, Inoue H, Uchiyama M, Yamochi T, Hosono OD, Nam H, Morimoto C (2006) T-cell activation via CD26 and caveolin-1 in rheumatoid synovium. Mod Rheumatol 16:3–13

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the 258/2009 ETT, the PD-73606 OTKA grants and the Hungarian Diabetes Association.

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The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Correspondence to Tímea Varga, Anikó Somogyi or Gábor Firneisz.

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Varga, T., Somogyi, A., Barna, G. et al. Higher Serum DPP-4 Enzyme Activity and Decreased Lymphocyte CD26 Expression in Type 1 Diabetes. Pathol. Oncol. Res. 17, 925–930 (2011). https://doi.org/10.1007/s12253-011-9404-9

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  • DOI: https://doi.org/10.1007/s12253-011-9404-9

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