c-peptide and Arthritis

Although both kidney and pancreas transplantation can restore renal and pancreatic endocrine functions, the accompanying immunosuppression may cause diminished glucose tolerance in some individuals. Therefore, we determined to what extent pancreas transplantation itself and the triple immunosuppressive therapy used in pancreas transplant recipients have adverse effects on insulin secretory reserve. Beta-cell secretory reserve was assessed by the method of glucose potentiation of arginine-induced insulin secretion in 25 normoglycemic pancreas recipients, 12 nondiabetic kidney recipients using the same immunosuppressive therapy, 3 psoriasis patients treated long term with cyclosporine, 5 arthritis patients treated long term with prednisone, and their respective sex-, age-, and body mass index-matched control subjects. Levels of fasting glucose, HbA1c, and glucose disappearance rates were normal in all subjects. During the glucose potentiation study, pancreas recipients had significantly less insulin secretion than control subjects (maximal acute response [ARmax] = 1,083 +/- 93% vs. 3,938 +/- 355%, P < 0.001). Insulin responses were also decreased in kidney recipients (ARmax = 2,296 +/- 290%) vs. control subjects (4,691 +/- 554%, P = 0.001) and in psoriasis patients treated with cyclosporine (ARmax = 2,153 +/- 390%) vs. control subjects (3,962 +/- 88%, P = 0.011), but not as extreme as that seen in pancreas recipients. No abnormalities were observed in arthritis patients treated with steroids. We conclude that normoglycemic pancreas and kidney transplant recipients receiving triple immunosuppressive therapy have diminished beta-cell secretory reserve. Because this defect was present in psoriasis patients treated long term with cyclosporine, but not in arthritis patients treated long term with prednisone, this adverse effect was probably caused in part by cyclosporine.

Topics: Adult; Arginine; Arthritis; Blood Glucose; C-Peptide; Cyclosporine; Diabetes Mellitus, Type 1; Female; Glucose; Humans; Immunosuppressive Agents; Insulin; Insulin Secretion; Islets of Langerhans; Kidney Transplantation; Male; Pancreas Transplantation; Prednisone; Psoriasis; Transplantation, Homologous

Immune recognition of the major structural proteins of rubella virus by peripheral blood mononuclear cells and synovial inflammatory infiltrates of a patient with documented chronic rubella associated arthritis was compared with responses of normal healthy rubella virus immunoreactive subjects to establish if there were unusual response patterns associated with rubella associated arthritis in this subject.. Synthetic peptides (16-33 amino acids in length) representing selected amino acid sequences of the rubella virus envelope (E1 and E2) and capsid (C) proteins were used in lymphocyte stimulation assays with peripheral blood mononuclear cells or synovial inflammatory infiltrates to determine T lymphocyte recognition of antigenic sites within the synthetic peptides. A rubella virus specific polymerase chain reaction was used to determine the persistence of rubella virus in the patient's cells.. The patient's peripheral blood mononuclear cells showed abnormally increased lymphoproliferative responses to three E1 synthetic peptides encompassing residues 219-234, 389-411, and 462-481, and one E2 synthetic peptide containing the sequence 50-72, of which the last three were predicted to contain T cell antigenic sites. Although the patient's peripheral blood mononuclear cells showed positive proliferative responses to C synthetic peptides, these were not unusual. The number of synthetic peptides within the E1, E2, and C panels recognised by the patient's peripheral blood mononuclear cells was greater than was previously observed in normal healthy subjects. The recognition of synthetic peptides by synovial inflammatory infiltrates was similar to peripheral blood mononuclear cells but the responses measured were lower. The polymerase chain reaction was negative for rubella virus detection in peripheral blood mononuclear cells and synovial inflammatory infiltrates.. Abnormally increased T cell recognition of antigenic sites within rubella virus E1 and E2 proteins observed in this patient with rubella associated arthritis suggests chronic antigenaemia due to persistent rubella virus in tissue sites other than peripheral blood mononuclear cells or synovial inflammatory infiltrates.

Topics: Aged; Arthritis; Arthritis, Infectious; C-Peptide; Chronic Disease; Female; Humans; Leukocytes, Mononuclear; Lymphocyte Activation; Polymerase Chain Reaction; Rubella virus; Synovial Fluid; Viral Envelope Proteins