Intraindividual changes of dipeptidyl peptidase-IV in peripheral blood of patients with rheumatoid arthritis are associated with the disease activity

Lucie Sromova, Petr Busek, Liliana Sedova, Aleksi Sedo

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). 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. 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). 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.