BACKGROUND:Screening pretransplantation recipient sera for percent panel reactive antibodies (%PRA) by an anti-human globulin (AHG) assay may identify recipients who are at risk for graft rejection or development of posttransplantation coronary artery disease. However, the pretransplantation AHG-%PRA does not always correlate with the occurrence of graft rejection or coronary artery disease.METHODS:We compared the predictive capacity of the AHG-%PRA with that of an enzyme-linked immunoassay (EIA)-based PRA assay that identifies immunoglobulin G bound to soluble human leukocyte antigen (sHLA) class I molecules from pooled platelets of 240 random donors (sHLA-EIA), and that of an EIA-based assay that detects immunoglobulin G anti-HLA class I antibodies bound to sHLA derived from individual HLA-typed cell cultures (PRA-STAT). The pretransplantation sera from 130 cardiac allograft recipients were comparatively tested and results evaluated.RESULTS:Although AHG-%PRA- and sHLA-EIA-determined PRA results were comparable, neither assay discriminated potential recipients at risk for rejection or coronary artery disease. However, cardiac allograft recipients with pretransplantation PRA-STAT sera > 10% were at risk for (1) graft rejection (77% vs 56%, p < .05); (2) more rejections/recipient (1.9 vs 1.0, p < .02); (3) graft rejection within 30 days (92% vs 38%, p < .001); or (4) development of coronary artery disease (48% vs 23%, p < .05) than recipients with pretransplantation PRA-STAT sera < 10%.CONCLUSIONS:PRA-STAT analysis of pretransplantation sera from potential cardiac allograft recipients may be more clinically informative about HLA alloimmunity and a better predictor of adverse clinical events than either AHG-%PRA- or sHLA-EIA-determined PRA.
A novel layer-by-layer (LbL) cation exchange membrane was prepared for heavy metal ions removal from water via electrodialysis. LBL membranes fabricated by coating of [chitosan-co-activated carbon nanoparticles] layer on polyvinyl chloride-based heterogeneous cation exchange membrane. Betterment in adherence of layers was achieved through glutaraldehyde cross linking. FTIR, FESEM, 3D-surface images and BET analysis were used for LBL membrane characterization. Membrane surface hydrophilicity, flux, membrane potential, transport number, and their permselectivity were studied. FTIR spectra confirm LbL formation decisively. FESEM images and BET analysis demonstrated that coating of second layer on PVC membrane led to a compact structure. LbL membrane showed smoother and more hydrophilic surface compared to pristine membrane. The transport number and permselectivity increased by deposition of second layer whereas sodium flux showed up-down trend. ED experiment showed good ability in heavy metal ions removal for LBL membrane that follows (Cu2+> Ni2+> Pb2+) sequence. EDX analysis showed a competitive adsorption for heavy metal ions on LBL membrane as (Pb2+> Cu2+≥Ni2+). The effect of ultrasonic waves on regeneration of fouled membranes by heavy metals was investigated. The results showed improved performance for the regenerated membrane. Mechanical resistance also improved by utilizing of ACNs in chitosan layer.
Increasing evidence suggests a detrimental effect of donor-specific antibodies directed against the human leukocyte antigen (HLA)-A, -B, and -DR loci on renal allograft outcomes. Limited data exist on the impact of de novo HLA-DQ antibodies. Over a 3-year period, we prospectively monitored 347 renal transplant recipients without pre-transplant donor-specific antibodies for their development de novo. After 26 months of follow-up, 62 patients developed donor-specific antibodies, of which 48 had a HLA-DQ antibody either alone (33 patients) or in combination with an HLA-A, -B, or -DR antibody (15 patients). Only 14 patients developed a donor-specific HLA-A, -B, or -DR antibody without a HLA-DQ antibody present. Acute rejection occurred in 21% of the HLA-DQ–only patients, insignificant when compared with 11% of patients without donor-specific antibodies. At the last follow-up, the mean serum creatinine and the fraction of patients with proteinuria were significantly higher in those that developed only HLA-DQ than those without antibodies. The 3-year graft survival was significantly worse when HLA-DQ antibodies were combined with non-DQ antibodies (52%) compared with HLA-DQ alone, non-DQ antibodies alone, or no antibodies (92–94%). Thus, our prospective monitoring study found that donor-specific HLA-DQ antibodies were the most common type detected and these antibodies may contribute to inferior graft outcomes. Ongoing surveillance is necessary to determine the long-term outcome of patients developing HLA-DQ donor-specific antibodies.
Distribution of cadaveric donor kidneys, based upon the donor-recipient HLA match grade, remains one of the major controversies in transplantation. To determine whether matching results in fewer rejection episodes and better graft survival, we retrospectively studied our single-center patient population of 683 cyclosporine-prednisone-treated primary cadaveric renal allograft recipients. For 237 recipients of well-matched HLA A, B kidneys (< or = 2 HLA A, B mismatches [MM]) the 1-, 3-, 5-, and 7-year graft survivals of 76%, 66%, 62%, and 61%, respectively, were not significantly different from those of 71%, 65%, 63%, and 63%, respectively, for the 446 poorly matched HLA A, B (> 2 HLA A, B MM) recipients. Similarly, the 1-, 3-, 5-, and 7-year graft survivals for the 307 recipients of well-matched HLA-DR kidneys (0 or 1 DR MM) of 74%, 65%, 63%, and 61%, respectively, were not significantly different from those of 72%, 65%, 63%, and 62%, respectively, for the 366 poorly matched (2 DR MM) recipients. Patient survivals were comparable at each time point for well- vs. poorly matched recipients. Similarly, donor-recipient HLA A, B, and DR matching was not beneficial in retransplant recipients who were transplanted following negative NIH and antiglobulin (AHG) crossmatches when testing both historical (high-PRA) and pretransplant sera. Since rejection episodes may be a more sensitive indicator of immune response than graft loss, we also analyzed the relationship between donor-recipient HLA match grade and posttransplant rejections. A total of 60% (n = 413) of recipients experienced no rejections and had 1-, 3-, 5-, and 7-year graft survivals of 82%, 78%, 74%, and 73%, respectively; 32% (n = 215) of patients who experienced 1 rejection had 1-, 3-, 5-, and 7-year graft survivals of 58%, 48%, 44%, and 43%, respectively (P < 0.001 for graft survival of 0 vs. 1 rejection). The remaining 8% (n = 55) of recipients experienced more than 1 (> 1) rejection and had 1-, 3-, 5-, and 7-year graft survivals of 62%, 38%, 36%, and 36%, respectively (P < 0.001 for graft survival of 0 vs. > 1 rejection and P < 0.01 for graft survival of 1 vs. > 1 rejection). The mean numbers of rejections/patient experienced by well-matched vs. poorly matched recipients were comparable and not significantly different.(ABSTRACT TRUNCATED AT 400 WORDS)