Background. Interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15, all T-cell growth factors(TCGFs), utilize the common IL-2 receptor γc chain as a critical signaling component in their receptor complexes. We have bred IL-2-/- and IL-4-/- double knockout (DKO) mice and showed vigorous islet allograft rejection by DKO hosts. The identity of TCGFs that support the IL-2- and IL-4-independent allograft rejection is unclear. Methods. We analyzed IL-9 gene expression in rejecting islet allografts in wild-type and in DKO mice, as well as in human renal transplant biopsy specimens, by reverse transcriptase polymerase chain reaction and compared the expression of IL-9 with that of other TCGFs. Results. IL-9 gene expression was not detected in rejecting murine islet allografts in either wild-type or DKO recipient mice despite robust expression of other TCGFs, including IL-7 and IL-15. IL-9 transcripts were also not expressed in any of the human renal transplant biopsies obtained 4 to 251 days after transplantation, regardless of the presence or absence of histological evidence of rejection. Despite expression of IL-9 by DKO splenic cells upon in vitro mitogenic stimulation, IL-9 alone was unable to stimulate the proliferation of concanavalin A-activated splenic leukocytes harvested from DKO mice. Conclusion. IL-9 is conspicuously absent despite vigorous expression of IL-2, IL-4, IL-7, and IL-15 genes during acute allograft rejection.
Of 110 consecutive renal allografts performed at Children's Hospital Medical Center 12 were in 11 patients aged 3 to 7 years. Patient and graft survival and linear growth were evaluated in these 11 children. All 11 are surviving, seven (64%) with functioning allografts 12 to 92 months after transplant. Six of these seven have normal renal function (on alternate day prednisone dose less than 0.7 mg/kg every two days plus daily azathioprine) and all seven have shown catch-up growth, reaching and maintaining normal height for age. An eighth patient, now returned to dialysis, grew from below the third percentile at age 3 years to the 25th percentile at age 8 years, after which renal function deteriorated. Three patients rapidly rejected allografts and have had decreased growth velocity for age. In contrast, although many of the remaining 76 patients who received 98 transplants after age 7 years are growing, none showed accelerated linear growth sufficient to catch up if below the third percentile for age or to cross centile lines if above. Neither the degree of pretransplant bone age retardation nor steroid dose per kilogram accounted for lack of growth acceleration of those more than 7 years of age. Despite small sample size, the growth of renal transplant recipients less than 7 years of age suggests that they are good, and in some ways, favored transplant candidates.
Background. We have shown previously that heightened expression of the cytotoxic lymphocyte (CL) effector genes perforin (P), granzyme B (GB), and Fas ligand (FasL), is closely correlated with acute allograft rejection, particularly when two or more target genes are up-regulated. Methods. We used quantitative reverse transcription-polymerase chain reaction to analyze CL gene expression from peripheral blood leukocytes (PBLs) and renal allograft biopsies in 31 paired samples of PBLs and renal tissue from 25 renal allograft recipients. Our aims were (1) to determine whether the expression of CL gene expression in PBLs correlates with expression of these genes in renal allograft biopsy tissue and (2) to determine whether CL gene expression in PBLs correlates with the histological diagnosis. Results. Coordinate gene expression in PBLs and acutely rejecting allografts was found in 9/11 (82%) for P, 07/11 (64%) for GB, and 10/11 (91%) for FasL. Coordinate absence was found in 15/20 (75%) for P, 17/20 (85%) for GB, and 16/20 (80%) for FasL in nonrejecting allografts. Furthermore, up-regulation of any two genes in PBLs correlated with pathological diagnosis of rejection with excellent positive (100%) and negative (95%) predictive values. Conclusion. Coordinate CL gene expression in PBLs and the allograft is usually detected. CL gene expression in PBLs is closely associated with a pathologic diagnosis of rejection. CL gene expression in PBLs may serve as noninvasive method of monitoring for renal allograft rejection.
We define delayed graft function (DGF) as the need for dialysis during the first post-transplant week. We analyzed 5272 transplants, of which 2486 were of living donor (LD) and 2786 were of cadaver donor (CD) origin. Twelve per cent (620/5272) of all patients developed DGF. Donor specific rates were 5.6% for LD and 19.1% for CD patients. Factors predictive of DGF in CD patients were: African-American race (25%), prolonged cold ischemia (24%), absence of T-cell induction antibody therapy and absence of HLA-DR matching. The relative risk (RR) for graft failure due to DGF was 6.02 (p < 0.001) in LD patients and 2.58 (p < 0.001) for CD recipients. Two-year graft survival (GS) in LD patients without DGF was 89.6%, compared to 41.6% for those with DGF (p < 0.001); in CD patients it was 80.2% and 49.5%, respectively (p < 0.001). Censoring for primary non-function, GS for LD patients with a functioning graft at 30 d post-transplant and no DGF was 91.5%, compared to 70.1% for those with DGF (p < 0.001); GS for CD patients was 83.8% and 68.7%, respectively (p < 0.001). However, when patients whose grafts had failed during the first year were censored no differences in GS were noted between patients with and without DGF for either LD or CD recipients. To determine whether DGF acts as an independent risk factor for graft failure, patients were segregated into four groups: rejection with DGF; rejection without DGF; DGF without rejection; and no DGF, no rejection. When these groups were compared DGF emerged as an independent risk factor for graft failure. This large study reviewing pediatric renal transplantation over 10 yr clearly delineates the role of DGF as a major risk factor for graft failure.
Background: Many pediatric transplant (TX) centers routinely monitor Epstein-Barr (EB) viral load (VL) by real time quantitative PCR and intervene to prevent post-transplant lymphoproliferative disorder (PTLD). Some children develop asymptomatic persistent VL (PVL). Outcome of different interventions in preventing PTLD and other undesired effects on acute rejection (AR), graft failure (GF) and function amongst children with asymptomatic PVL is not known. Methods: NAPRTCS centers invited to enter data on children with asymptomatic PVL (≥ 6 months) into the EB VL registry. Comparison group included children into the NAPRTCS TX arm during the same period without PVL or VL monitoring. EB VL were arbitrarily divided into low (1-10), medium (>10-100) and high (>100times detection limit for the center) ratio. Results: Of 645 children (18 centers), 85 (13.2%) developed onset of PVL at a mean of 6.4 ± 6.3 months post-TX. PVL children were more likely to be younger (< 5 years) at TX and less likely to be African-American and majority (75.3%) was mismatched for EBV (donor EBV IgG positive and recipient negative). Thymoglobulin induction was used in 29.4% children with PVL versus 37% in controls (p=ns). PTLD developed in 7/85 (8.2%) children with PVL versus 5/560 (0.9%) controls (p < 0.0001). EB VL ratios were not different in those with and without PTLD. EB PVL as time varying covariate did not affect patient survival, GF and AR (HR, 0.85, 0.53 and 0.99). The change in GFR overtime in children with PVL was comparable to controls. Conclusion: Children with PVL (actual load not predictive) are at increased risk for PTLD, but not for AR, death, GF or loss of graft function.
 scale(.12937)'%3e %3csvg width='12' viewBox='-120 -190.223125 240 309.188274' height='15.459'%3e %3cpath d='m110.26-19.478l9.74-143.75a280.22 280.22 0 0 0 -240 0l9.74 143.75a155.61 155.61 0 0 0 110.26 138.45 155.61 155.61 0 0 0 110.26 -138.45' fill='%23005da4'/%3e %3cpath d='m-90 0a138.29 138.29 0 0 0 90 100.77 138.29 138.29 0 0 0 90 -100.77l-45-60-18 24-27-54-27 54-18-24-45 60' fill='%23fff'/%3e %3cg id='wave' fill='%23005da4' transform='scale(5) translate(0 5.1962)'%3e %3cpath d='m-17.196-2.1962a6 6 0 0 0 8.1962 2.1962 6 6 0 0 1 6 0 6 6 0 0 0 6 0 6 6 0 0 1 6 0 6 6 0 0 0 8.1962 -2.1962v1.732a6 6 0 0 1 -8.1962 2.1962 6 6 0 0 0 -6 0 6 6 0 0 1 -6 0 6 6 0 0 0 -6 0 6 6 0 0 1 -8.1962 -2.1962z'/%3e %3c/g%3e %3cuse xlink:href='%23wave' transform='translate(0 17.321)'/%3e %3cg id='s' transform='translate(0,-120) scale(2.25)'%3e %3cpath stroke-width='.2' d='m0-5l1 3.2679 3.3301-0.7679-2.3301 2.5 2.3301 2.5-3.3301-0.7679-1 3.2679-1-3.2679-3.3301 0.7679 2.3301-2.5-2.3301-2.5 3.3301 0.7679z' fill='%23fd0'/%3e %3c/g%3e %3cuse xlink:href='%23s' transform='translate(-33.75,-45)'/%3e %3cuse xlink:href='%23s' transform='translate(33.75,-45)'/%3e %3cpath d='m-111.58-167.05l9.96 146.99a146.95 146.95 0 0 0 101.62 129.95 146.95 146.95 0 0 0 101.62 -129.95l9.96-146.99a280.22 280.22 0 0 0 8.42 3.82l-9.74 143.75a155.61 155.61 0 0 1 -110.26 138.45 155.61 155.61 0 0 1 -110.26 -138.45l-9.74-143.75a280.22 280.22 0 0 0 8.42 -3.82' fill='%23ed1c24'/%3e %3c/svg%3e %3c/g%3e %3c/svg%3e)
