Activity and expression of dipeptidyl peptidase IV on peripheral blood mononuclear cells in patients with early steroid and disease modifying antirheumatic drugs naïve rheumatoid arthritis

Grujić, M; Matic, Ivana; Crnogorac,; Ad, Velickovic; Kolundžija, Branka; Cordero, Oscar J.; Juranić, Zorica D.; Prodanovic, S.; Zlatanović, Maja; Babič, Dunja Z.; Damjanov, Nemanja

doi:10.1515/cclm-2015-1279

Cited by 16 publications

(15 citation statements)

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“…This apparent contradictory result may explain the positive correlation of DPP-4 with disease activity observed in our patients with RA. Of note, a recent study involving 50 patients with RA revealed a decrease in DPP-4 serum activity but not in DPP-4/CD26 expression [ 34 ]. In another study involving 27 patients with RA, there was also an elevation in blood plasma DPP-4 but a decrease of DPP-4/CD26 in peripheral blood mononuclear cells after clinical improvement following treatment [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Incretins in patients with rheumatoid arthritis

et al. 2017

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BackgroundThe precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients.MethodsWe conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects.ResultsInsulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (β coefficient 46, 95% CI 6–87, p = 0.026) and Clinical Disease Activity Index (β coefficient 7.74, 95% CI 1.29–14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with β-cell function (HOMA2 of β-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response.ConclusionsThe incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1431-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Incretins in patients with rheumatoid arthritis

et al. 2017

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“…CXCL10 was claimed to be the most relevant chemokine biomarker in patients with rheumatoid arthritis, but also large numbers of CD26-expressing cells were found in these patients ( 158 – 160 ). Remarkably, although rheumatoid arthritis was not associated with altered levels of soluble CD26, the specific activity of the enzyme was reduced, probably because of glycosylation ( 161 , 162 ). In mice, inhibition of CD26 was found to protect CXCL10 from inactivation, resulting in enhanced T cell infiltration into the tumor tissue, thereby improving not only the natural antitumor immunity but also the response to existing immunotherapies ( 156 ).…”

Section: Regulation Of Ifn-inducible Cxcr3 Ligand Activity By Posttramentioning

confidence: 99%

Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of Interferon-Inducible CXC Chemokine Receptor 3 Ligands

et al. 2018

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The inflammatory chemokines CXCL9, CXCL10, and CXCL11 are predominantly induced by interferon (IFN)-γ and share an exclusive chemokine receptor named CXC chemokine receptor 3 (CXCR3). With a prototype function of directing temporal and spatial migration of activated T cells and natural killer cells, and inhibitory effects on angiogenesis, these CXCR3 ligands have been implicated in infection, acute inflammation, autoinflammation and autoimmunity, as well as in cancer. Intense former research efforts led to recent and ongoing clinical trials using CXCR3 and CXCR3 ligand targeting molecules. Scientific evidence has claimed mutual redundancy, ligand dominance, collaboration or even antagonism, depending on the (patho)physiological context. Most research on their in vivo activity, however, illustrates that CXCL9, CXCL10, and CXCL11 each contribute to the activation and trafficking of CXCR3 expressing cells in a non-redundant manner. When looking into detail, one can unravel a multistep machinery behind final CXCR3 ligand functions. Not only can specific cell types secrete individual CXCR3 interacting chemokines in response to certain stimuli, but also the receptor and glycosaminoglycan interactions, major associated intracellular pathways and susceptibility to processing by particular enzymes, among others, seem ligand-specific. Here, we overview major aspects of the molecular properties and regulatory mechanisms of IFN-induced CXCR3 ligands, and propose that their in vivo non-redundancy is a reflection of the unprecedented degree of versatility that seems inherent to the IFN-related CXCR3 chemokine system.

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“…type II diabetes and metabolic syndrome) , auto‐immunity (i.e. multiple sclerosis, rheumatoid arthritis) and cancer (i.e. B‐cell leukaemia, hepatocellular carcinoma, bladder cancer) .…”

Section: Discussionmentioning

confidence: 99%

Systemic DPP4 activity is reduced during primary HIV‐1 infection and is associated with intestinal RORC⁺CD4⁺ cell levels: a surrogate marker candidate of HIV‐induced intestinal damage

et al. 2018

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IntroductionCombined anti‐retroviral therapy (cART) transformed HIV‐1 from a deadly disease into a chronic infection, but does not cure HIV infection. It also does not fully restore HIV‐induced gut damage unless administered extremely early after infection. Additional biomarkers are needed to evaluate the capacity of therapies aimed at HIV remission/cure to restore HIV‐induced intestinal immune damage and limit chronic inflammation. Herein, we aimed to identify a systemic surrogate marker whose levels would reflect gut immune damage such as intestinal Th17 cell loss starting from primary HIV‐1 infection.MethodsBiomarker discovery approaches were performed in four independent cohorts, covering HIV‐1 primary and chronic infection in 496 naïve or cART‐treated patients (Amsterdam cohort (ACS), ANRS PRIMO, COPANA and CODEX cohorts). The concentration and activity of soluble Dipeptidylpeptidase 4 (sDPP4) were quantified in the blood from these patients, including pre‐ and post‐infection samples in the ACS cohort. For quantification of DPP4 in the gut, we utilized two non‐human primate models, representing pathogenic (macaque) and non‐pathogenic (African green monkey) SIV infection. Four gut compartments were analysed in each animal model (ileum, jejunum, colon and rectum) for quantification of DPP4,RORC and TBX21 gene expression in sorted CD4+ cells. To analyse if sDPP4 levels increase when Th17 cells were restored, we quantified sDPP4 in plasma from SIV‐infected macaques treated with IL‐21.ResultsWe showed that sDPP4 levels were strongly decreased in primary HIV‐1 infection. Strikingly, sDPP4 levels in primary HIV‐1 infection predicted time to AIDS. They were not increased by cART in chronic HIV‐1 infection (median 36 months on cART). In the gut of SIV‐infected non‐human primates, DPP4 mRNA was higher in CD4+ than CD4− leucocytes. DPP4 specifically correlated with RORC expression, a Th17 marker, in CD4+ cells from the intestine. We further demonstrated that sDPP4 activity levels were increased in animals treated with IL‐21 and that this increase was associated with restoration of the Th17 compartment and reduced inflammation. Furthermore, DPP4 mRNA levels in small intestine CD4+ cells positively correlated with circulating DPP4 activity.ConclusionThese data provide evidence that blood sDPP4 levels could be useful as a correlate for HIV‐induced intestinal damage.

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Activity and expression of dipeptidyl peptidase IV on peripheral blood mononuclear cells in patients with early steroid and disease modifying antirheumatic drugs naïve rheumatoid arthritis

Abstract: Our results show that a decrease in DPPIV serum activity, but not CD26 expression, is present in an early stage of rheumatoid arthritis.

Cited by 16 publications

References 30 publications

Incretins in patients with rheumatoid arthritis

Incretins in patients with rheumatoid arthritis

Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of Interferon-Inducible CXC Chemokine Receptor 3 Ligands

Systemic DPP4 activity is reduced during primary HIV‐1 infection and is associated with intestinal RORC⁺CD4⁺ cell levels: a surrogate marker candidate of HIV‐induced intestinal damage

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Activity and expression of dipeptidyl peptidase IV on peripheral blood mononuclear cells in patients with early steroid and disease modifying antirheumatic drugs naïve rheumatoid arthritis

Abstract: Our results show that a decrease in DPPIV serum activity, but not CD26 expression, is present in an early stage of rheumatoid arthritis.

Cited by 16 publications

References 30 publications

Incretins in patients with rheumatoid arthritis

Incretins in patients with rheumatoid arthritis

Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of Interferon-Inducible CXC Chemokine Receptor 3 Ligands

Systemic DPP4 activity is reduced during primary HIV‐1 infection and is associated with intestinal RORC+CD4+ cell levels: a surrogate marker candidate of HIV‐induced intestinal damage

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Systemic DPP4 activity is reduced during primary HIV‐1 infection and is associated with intestinal RORC⁺CD4⁺ cell levels: a surrogate marker candidate of HIV‐induced intestinal damage