apyrase and Kidney-Failure--Chronic

Regulatory T cells (Treg) are important in mediating immune tolerance and outcomes of allotransplantation. CD4. CD4

Topics: Acute Disease; Adult; Aged; Allografts; Antigens, CD; Apyrase; Biomarkers; Case-Control Studies; Cell Proliferation; Cells, Cultured; Coculture Techniques; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Interleukin-2 Receptor alpha Subunit; Kidney Failure, Chronic; Kidney Transplantation; Lymphocyte Activation; Male; Middle Aged; Phenotype; Prospective Studies; Risk Factors; T-Lymphocytes, Regulatory; Time Factors; Transplantation Tolerance; Treatment Outcome

We have shown that CD39 and CD73 are coexpressed on the surface of murine CD4+ Foxp3+ regulatory T cells (Treg) and generate extracellular adenosine, contributing to Treg immunosuppressive activity. We now describe that CD39, independently of CD73, is expressed by a subset of blood-derived human CD4+ CD25+ CD127lo Treg, defined by robust expression of Foxp3. A further distinct population of CD4+ CD39+ T lymphocytes can be identified, which do not express CD25 and FoxP3 and exhibit the memory effector cellular phenotype. Differential expression of CD25 and CD39 on circulating CD4+ T cells distinguishes between Treg and pathogenic cellular populations that secrete proinflammatory cytokines such as IFNγ and IL-17. These latter cell populations are increased, with a concomitant decrease in the CD4+ CD25+ CD39+ Tregs, in the peripheral blood of patients with renal allograft rejection. We conclude that the ectonucleotidase CD39 is a useful and dynamic lymphocytes surface marker that can be used to identify different peripheral blood T cell-populations to allow tracking of these in health and disease, as in renal allograft rejection.

Topics: Antigens, CD; Apyrase; CD4 Antigens; CD4-Positive T-Lymphocytes; Graft Rejection; Humans; Immunologic Memory; Interferon-gamma; Interleukin-17; Interleukin-2 Receptor alpha Subunit; Kidney Failure, Chronic; Kidney Transplantation; Phenotype; Pyrophosphatases; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Th17 Cells

The vascular ectonucleotidase ENTPD1 protects against renal injury and modulates glucose homeostasis in mouse models. We sought to determine whether human variation in ENTPD1 influences predisposition to diabetes or diabetic nephropathy.. We analyzed ENTPD1 single nucleotide polymorphisms (SNPs) in 363 African American control subjects, 380 subjects with type 2 diabetes and end-stage renal disease (DM-ESRD), and 326 subjects with ESRD unrelated to diabetes (non-DM-ESRD). Using human cell lines, we correlated disease-associated ENTPD1 haplotypes with ENTPD1 gene expression. Finally, we studied consequences of ENTPD1 deletion in a mouse model of type 2 diabetes (db/db).. A common ENTPD1 two-SNP haplotype was associated with increased risk for DM-ESRD (P = 0.0027), and an uncommon four-SNP haplotype was associated with protection against DM-ESRD (P = 0.004). These haplotypes correlated with ENTPD1 gene expression levels in human cell lines in vitro. Subjects with high ENTPD1-expressing haplotypes were enriched in the DM-ESRD group. By crossing ENTPD1-null mice with db mice, we show that ENTPD1 deletion has prominent effects on metabolic syndrome traits. Specifically, deletion of ENTPD1 lowered glucose levels in control (db/-) mice with one functional leptin receptor and dramatically lowered weights in db/db mice with no functional leptin receptors. Similar effects were seen in aged ENTPD1-null mice with normal leptin receptors.. ENTPD1 polymorphisms appear to influence susceptibility to type 2 diabetes and/or diabetic nephropathy in African Americans. Studies in human cell lines and in vivo mouse data support a potential role for ENTPD1 genetic variation in susceptibility to type 2 diabetes.

Topics: Animals; Antigens, CD; Apyrase; Black People; Cell Line; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Humans; Kidney Failure, Chronic; Mice; Mice, Knockout; Polymorphism, Single Nucleotide; Sequence Deletion

The activities of the enzymes NTPDase (E.C.3.6.1.5, apyrase, ATP diphosphohydrolase, ecto-CD 39) and 5'-nucleotidase (E.C.3.1.3.5, CD 73) were analyzed in platelets from patients with chronic renal failure (CRF), both undergoing hemodialysis treatment (HD) and not undergoing hemodialysis (ND), as well as from a control group. The results showed an increase in platelet NTPDase activity in CRF patients on HD treatment (52.88%) with ATP as substrate (P<0.0001). ADP hydrolysis was decreased (33.68% and 39.75%) in HD and ND patients, respectively. In addition, 5'-nucleotidase activity was elevated in the HD (160%) and ND (81.49%) groups when compared to the control (P<0.0001). Significant correlation was found among ATP, ADP and AMP hydrolysis and plasma creatinine and urea levels (P<0.0001). Patients were compared statistically according the time of hemodialysis treatment. We found enhanced NTPDase and 5'-nucleotidase activities between 49 and 72 months on HD patients. Our result suggests the existence of alterations in nucleotide hydrolysis in platelets of CRF patients. Possibly, this altered nucleotide hydrolysis could contribute to hemostasis abnormalities found in CRF.

Topics: 5'-Nucleotidase; Adenine; Analysis of Variance; Antigens, CD; Apyrase; Blood Platelets; Creatine; Humans; Kidney Failure, Chronic; Renal Dialysis; Time Factors; Urea