Subject(s)
Lupus Erythematosus, Systemic/immunology , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Animals , Antibodies, Antinuclear/blood , Disease Models, Animal , Female , Immunoglobulin G/blood , Immunoglobulin Isotypes/blood , Immunosuppressive Agents , Lupus Erythematosus, Systemic/prevention & control , Mice , Mice, Inbred StrainsABSTRACT
BACKGROUND: The aim of this study was investigation of the HLA-I cross-reactive group (CREG)-specific antibodies (Abs) in sera from patients with a failed renal transplant and from nontransplanted patients. METHODS: A total of 5292 sera from 570 patients awaiting kidney transplantation were screened for the presence of HLA-I CREG-specific Abs. Patients who had never received a transplant (group A), and those with a previous transplant and Abs either not related (group B) or related to donor specificities (group C) were studied. A further division was made for Abs directed against specificities either included in (intra-CREG) or not included in patients' HLA-CREG (extra-CREG). RESULTS: Twelve of 24 (50%) Abs produced in response to mismatched donor HLA specificities after a failed graft were intra-CREG Abs, compared to 7 of 39 (18%) Abs that were not transplant-related. CONCLUSIONS: Renal grafts showed a stronger immunogenicity than other sources of allosensitization. Our data also suggest that CREG matching may not be useful for renal allocation.
Subject(s)
Antibodies/immunology , Kidney Transplantation/immunology , Repressor Proteins/immunology , Antibody Formation , HLA Antigens/immunology , Histocompatibility Testing , Humans , Reoperation , Treatment Failure , Waiting ListsABSTRACT
BACKGROUND: Recent studies have demonstrated that a high concentration of phosphate directly stimulates parathyroid hormone (PTH) secretion. High serum levels of phosphate are usually observed in patients with end-stage renal disease. The aim of the present study was to evaluate whether serum phosphate concentration had an acute effect on PTH secretion in hemodialysis patients. The levels of serum phosphate were manipulated during the hemodialysis session by using a phosphate free dialysate or a dialysate with a high content of phosphate. METHODS: Ten stable hemodialysis patients with PTH values above 300 pg/ml were included in the study. A PTH-calcium curve was obtained during both high phosphate and phosphate free hemodialysis. RESULTS: The serum phosphate concentration remained high (2.17 +/- 0.18 mM) throughout the high phosphate hemodialysis and decreased progressively to normal levels (1.02 +/- 0.06 mM) during the phosphate free hemodialysis. The serum PTH levels at maximal inhibition by hypercalcemia (minimal PTH) were greater during the high phosphate than the phosphate free hemodialysis (413 +/- 79 vs. 318 +/- 76 pg/ml, P < 0.003). In all patients the values of minimum PTH were greater during the high phosphorus than the phosphorus free hemodialysis. The values of maximally stimulated PTH during hypocalcemia and the set point of the PTH-calcium curve were similar during the high phosphate and the phosphate free hemodialysis. CONCLUSION: The maintenance of high serum phosphorus levels during hemodialysis prevented, in part, the inhibition of PTH secretion by calcium, which strongly suggests that in hemodialysis patients high serum phosphate contributes directly to the elevation of PTH levels despite normal or high serum calcium concentration.
