Intraindividual changes of dipeptidyl peptidase-IV in peripheral blood of patients with rheumatoid arthritis are associated with the disease activity.
BACKGROUND
Dipeptidyl peptidase-IV (DPP-IV) is suggested to contribute to the pathogenesis of several autoimmune diseases. The aim of this study was to evaluate the association of DPP-IV presence in blood plasma and mononuclear cells with the disease activity in rheumatoid arthritis (RA).


METHODS
Patients with active RA (n = 27) were examined at the study enrolment and a follow-up examination was performed after the regression of the joint effusions and at least 6 months after the first investigation. The control group comprised patients with a noninflammatory joint disease, i.e. osteoarthritis (OA; n = 15). The DPP-IV-like enzymatic activity was measured by a kinetic fluorimetric method, the concentration of DPP-IV in the blood plasma was determined using ELISA and the expression of DPP-IV in leukocytes was assayed by flow cytometry.


RESULTS
Blood plasma DPP-IV-like enzymatic activity (median ± SD 220.15 ± 83.6 pkat/mL in RA vs. 376.9 ± 144.9 pkat/mL in OA, p < 0.001) and concentrations (median ± SD 465.1 ± 215.6 ng/mL in RA vs. 953.3 ± 368.4 ng/mL in OA, p < 0.001) were lower in patients with active RA compared to OA. In RA patients, the blood plasma DPP-IV-like enzymatic activity negatively correlated with the CRP concentration (r = -0.39, p = 0.044). No significant differences were observed in the DPP-IV-like enzymatic activity and DPP-IV expression in blood mononuclear cells between the RA and OA groups. At follow-up, 18 RA patients had a less active disease as demonstrated by an improved DAS28 score. In this group, comparison of the entry and the follow-up values in individual patients revealed an increase of the blood plasma DPP-IV-like enzymatic activity (median ± SD 141 ± 46% of the patient's entry values, p = 0.011) and DPP-IV concentration (median ± SD 168 ± 25%, of the patient's entry values, p = 0.033). In contrast to the blood plasma, the DPP-IV expression in blood mononuclear cells was reduced in these patients as evidenced by a decrease in the cell surface DPP-IV-like enzymatic activity as well as the median fluorescence intensity of DPP-IV staining in lymphocytes (median ± SD 66 ± 56%, p = 0.018 and 63 ± 31 % of the patient's entry values, p = 0.005, respectively).


CONCLUSIONS
The association between RA activity and the changes in blood plasma and blood mononuclear cell DPP-IV in individual patients supports the possible relationship of DPP-IV to RA pathophysiology.
Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology of the First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic. lsrom@lf1.cuni.cz.
Lucie
L
Sromova
Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology of the First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic. busekpetr@seznam.cz.
Petr
P
Busek
Institute of Rheumatology, Na Slupi 4, 128 50, Prague, Czech Republic. sedo@revma.cz.
Liliana
L
Sedova
Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology of the First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic. aleksi@cesnet.cz.
Aleksi
A
Sedo
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D018819:Dipeptidyl Peptidase 4