Background/Purpose:

Dipeptidyl peptidase IV (DPP-IV, CD26), a protease cleaving N-terminal X-Pro dipeptides from selected proteins including chemokines is expressed both as a soluble form and on the surface of various immune and non-immune cells. In rheumatoid arthritis (RA), low DPP-IV/sCD26 activity has been shown in serum and synovial fluid, with restoration of normal levels of activity in patients treated with anti-TNF-alfa therapy. The objective of our study was to study DPP-IV/sCD26 in RA patients and its correlation with disease activity and the different therapies received.

Methods:

Patients diagnosed with RA according the 1987 ACR classification criteria for RA were included. The degree of RA activity was evaluated by using DAS 28, acute-phase reactants and hemoglobin levels. Data about all the medications and their doses were collected.

Expression levels of CD26 on white blood cells were evaluated by flow cytometry analysis and the serum levels of the enzyme DPP-IV by ELISA. All laboratory tests were performed blindly. An institutional review board approved this study. All patients gave written informed consent.

To evaluate the correlation among clinical and serological variables, bivariate analysis was performed (SPSS 16.0).

Results:

Sixty-eight patients were recruited: 75% woman, median age (IR): 57.1 years (18.6), median disease duration (IR): 9.8 years (14.0). Regarding the RA activity variables, median DAS28, ESR, CRP and Hemoglobin (IR) were: 3.4 (1.7), 30.5 (31), 4.1 (10) and 13.3 (2.2), respectively.

There were not significant differences in the percentages of CD26 expressing T helper subsets in RA patients treated vs. non-treated with biologics. However, we found a statistically significant raise in the levels of cell surface CD26 expression (mean of fluorescence intensity, MFI) in the T helper effector/memory CD45RO+ CD26+ or CD26high subset in patients on biologic therapy compared with those without biologic therapy (p = 0.03).

Overall, the levels of cell surface CD26 expression measured by MFI in the T helper effector/memory CD45RO+ CD26+ correlated significantly with the activity of the disease measured by DAS28 score (Pearson’s CC: 0.4, p = 0.001).

Conclusion:

Higher levels of plasma membrane CD26 (measured by MIF) may be related with the decreased circulating sCD26 levels in RA, and these levels correlates with the disease activity. Patients on biologic therapies showed increased levels of plasma membrane CD26 in a similar way to the restoration of circulating levels of CD26 associated with anti-TNF-alfa therapy described in the literature. These changes may be also related with the number of Th17 cells, which express high levels of CD26, this hypothesis being under study. Thus, different therapies may influence distinctly the CD26-mediated regulation of the chemotactic SDF-1/CXCR4 axis of inflammation.

Reference

Mavropoulos JC, Cuchacovich M, Llanos C, et al. Anti-tumor necrosis factor-alpha therapy augments dipeptidyl peptidase IV activity and decreases autoantibodies to GRP78/BIP and phosphoglucose isomerase in patients with rheumatoid arthritis. J Rheumatol 2005;32:2116-24.

 Disclosure: this study was funded by an unrestricted medical grant from Pfizer.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dipeptidyl-peptidase-iv-dpp-iv-cd26-levels-in-patients-with-rheumatoid-arthritis-treated-with-biologic-therapies-and-correlation-with-the-activity-of-the-disease/