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Humoral Rejection (humoral + rejection)
Kinds of Humoral Rejection Selected AbstractsAcute Humoral Rejection in an ABO Compatible Combined Liver,Kidney Transplant,The Kidney Is Not Always ProtectedAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009T. W. Reichman Combined liver,kidney transplantation has become a common practice for the treatment of patients with concurrent end-stage renal disease and end-stage liver disease. Liver transplantation in the setting of multiorgan transplantation is thought to have a protective effect against humoral rejection even when a positive crossmatch is obtained prior to surgery. In most centers, a pre liver,kidney transplant crossmatch is rarely performed because of the known immunoprotective effect of the liver allograft. In this report, a case of acute humoral rejection in the kidney allograft after a combined liver,kidney transplant is described. Although humoral rejection was treated using plasmapheresis, intravenous immunoglobulin and rituximab, the kidney required 3 months to recover function and finally progressed to chronic allograft nephropathy. A heightened index of suspicion for acute humoral rejection of the renal allograft is necessary when performing combined liver,kidney transplants to highly sensitized patients due to previous organ transplants. [source] Evidence for Humoral Rejection of a Pancreatic Islet Graft and Rescue with Rituximab and IV Immunoglobulin TherapyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009L. Kessler We describe the decline in islet function, in relation to HLA sensitization, in an islet transplant recipient and the recovery of this function after treatment with anti-CD20 monoclonal antibody and IV immunoglobulins. A 51-year-old woman with type 1 diabetes received one intraportal islet infusion. Following this transplantation, she became insulin independent. A search for HLA antibodies by using an ELISA technique remained consistently negative for HLA class I and II. It was only 2 years after the islet transplantation that this search became positive against class II antigens, reaching a peak of reactivity concomitantly with the appearance of a deterioration of glucose control requiring low-dose insulin therapy. Luminex® screening and single-antigen assays then revealed the presence of both nondonor-specific and donor-specific antibodies against HLA class II molecules. This immunization, already present in the pretransplant serum, had increased during the 6 months preceding the clinical deterioration. Since these data nevertheless pointed to antibody-mediated rejection of the islet allograft, treatment with anti-CD20 monoclonal antibody and IV immunoglobulins was initiated. One month later, the search by ELISA for antibodies against HLA class II antigens became negative, the Luminex® tests normalizing more gradually. As the result of an improvement in glucose control, the patient was again insulin-free. [source] Acute Humoral Rejection in Kidney Allograft Following a Third-Party Arterial TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2006S. Ferrari-Lacraz No abstract is available for this article. [source] Peritubular Capillary Damage in Acute Humoral Rejection: An Ultrastructural Study on Human Renal AllograftsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2005P. Lipták The ultrastructural features of peritubular capillary (PC) damage was studied in 12 kidney allografts with acute humoral rejection (AHR). AHR manifested in diffuse linear PC staining for C4d, and histology consistent with Banff grade III in 7 recipients and Banff grade II in 5. Allografts with acute tubular necrosis served as controls. First biopsies (post-transplantation day 16.2 ± 2.2): The intra-capillary exudate comprised monocytes (59%), polymorphonuclears (14%), lymphocytes (12%) and not otherwise specified mononuclears (15%). Three patterns of focal PC endothelial injury were observed: lysis, an increased rate of apoptosis and fragmentation. No correlation was found between the respective damage types and the inflammatory cell types or the Banff grades. Controls revealed endothelial swelling, detachment from basement membrane and fragmentation. Follow-up biopsies: Monocytes transformed into macrophages intra-luminally. The reparative changes comprised endothelial cytoplasmic protrusions, binucleated endothelial cells and capillary sprouts. Early transplant capillaropathy and transplant glomerulopathy were noted in 2 recipients. Literature data indicate that lysis is mediated by anti-HLA alloantibodies; apoptosis, demonstrated first in the present study, may be induced by non-HLA-type anti-endothelial antibodies. Fragmentation is caused by ischemia. Ongoing endothelial injury leads to transplant capillaropathy and transplant glomerulopathy, the characteristic lesions of chronic rejection. [source] Plasmapheresis as rescue therapy in accelerated acute humoral rejection,JOURNAL OF CLINICAL APHERESIS, Issue 3 2003Kottarathil A. Abraham Abstract Accelerated acute humoral rejection (AHR) continues to occur in renal transplantation despite improved crossmatching, with potentially devastating consequences. Between 1 June 1998 and 31 December 2000, 440 renal transplants were performed in our center. AHR was diagnosed by the demonstration of typical pathological features on renal histology and positive direct immunofluorescence or detection of anti-HLA antibodies in serum. AHR developed in 20 (4.5%) of our renal transplant recipients, nine male and eleven female at an average of 16.3 days post transplantation. All of these patients had a negative current cytotoxic crossmatch prior to transplantation. The median serum creatinine at diagnosis was 5.96 mg/dL, and 83% of these individuals developed oliguric renal failure requiring dialysis after having initially attained good graft function (median of best serum creatinine before AHR was 2.64 mg/dL). The 18 recipients who had not infarcted their grafts at the time of diagnosis of AHR received plasmapheresis in conjunction with intensification of their immunosuppressive regimen. This regimen was successful in reversing AHR in 78% of those treated with apheresis. In the 14 responders, graft survival at 6 months was 100% and at 12 months was 91%. Median serum creatinine at 6 and 12 months was 1.26 and 1.33 mg/dL, respectively. Patients received an average of 8.1 plasma exchanges. However, responders received a significantly higher frequency of plasmapheresis (P = .0053), despite undergoing a similar number of exchanges overall. Plasmapheresis appears to be an effective modality for reversing AHR and maintaining graft function. J. Clin. Apheresis 18:103,110, 2003. © 2003 Wiley-Liss, Inc. [source] Bortezomib as the Sole Post-Renal Transplantation Desensitization Agent Does Not Decrease Donor-Specific Anti-HLA AntibodiesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010R. Sberro-Soussan Persistence of donor-specific anti-HLA antibodies (DSA) associated with antibody-mediated graft injuries following kidney transplantation predicts evolution toward chronic humoral rejection and reduced graft survival. Targeting plasma cells, the main antibody-producing cells, with the proteasome inhibitor bortezomib may be a promising desensitization strategy. We evaluated the in vivo efficacy of one cycle of bortezomib (1.3 mg/m2× 4 doses), used as the sole desensitization therapy, in four renal transplant recipients experiencing subacute antibody-mediated rejection with persisting DSA (>2000 [Mean Fluorescence Intensity] MFI). Bortezomib treatment did not significantly decrease DSA MFI within the 150-day posttreatment period in any patient. In addition, antivirus (HBV, VZV and HSV) antibody levels remained stable following treatment suggesting a lack of efficacy on long-lived plasma cells. In conclusion, one cycle of bortezomib alone does not decrease DSA levels in sensitized kidney transplant recipients in the time period studied. These results underscore the need to evaluate this new desensitization agent properly in prospective, randomized and well-controlled studies. [source] B-Cell Immunity in the Context of T-Cell Tolerance after Combined Kidney and Bone Marrow Transplantation in HumansAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009F. Porcheray Five patients with end-stage kidney disease received combined kidney and bone marrow transplants from HLA haploidentical donors following nonmyeloablative conditioning to induce renal allograft tolerance. Immunosuppressive therapy was successfully discontinued in four patients with subsequent follow-up of 3 to more than 6 years. This allograft acceptance was accompanied by specific T-cell unresponsiveness to donor antigens. However, two of these four patients showed evidence of de novo antibodies reactive to donor antigens between 1 and 2 years posttransplant. These humoral responses were characterized by the presence of donor HLA-specific antibodies in the serum with or without the deposition of the complement molecule C4d in the graft. Immunofluorescence staining, ELISA assays and antibody profiling using protein microarrays demonstrated the co-development of auto- and alloantibodies in these two patients. These responses were preceded by elevated serum BAFF levels and coincided with B-cell reconstitution as revealed by a high frequency of transitional B cells in the periphery. To date, these B cell responses have not been associated with evidence of humoral rejection and their clinical significance is still unclear. Overall, our findings showed the development of B-cell allo- and autoimmunity in patients with T-cell tolerance to the donor graft. [source] Acute Humoral Rejection in an ABO Compatible Combined Liver,Kidney Transplant,The Kidney Is Not Always ProtectedAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009T. W. Reichman Combined liver,kidney transplantation has become a common practice for the treatment of patients with concurrent end-stage renal disease and end-stage liver disease. Liver transplantation in the setting of multiorgan transplantation is thought to have a protective effect against humoral rejection even when a positive crossmatch is obtained prior to surgery. In most centers, a pre liver,kidney transplant crossmatch is rarely performed because of the known immunoprotective effect of the liver allograft. In this report, a case of acute humoral rejection in the kidney allograft after a combined liver,kidney transplant is described. Although humoral rejection was treated using plasmapheresis, intravenous immunoglobulin and rituximab, the kidney required 3 months to recover function and finally progressed to chronic allograft nephropathy. A heightened index of suspicion for acute humoral rejection of the renal allograft is necessary when performing combined liver,kidney transplants to highly sensitized patients due to previous organ transplants. [source] Mechanisms of Alloantibody Production in Sensitized Renal Allograft RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009M. D. Stegall While clinical protocols have been developed to allow for successful kidney transplantation in patients with high levels of donor-specific alloantibody (DSA), significant limitations still exist including high rates of early humoral rejection and decreased long-term graft survival compared to conventional transplants. A better understanding of the mechanisms of alloantibody production at baseline and at various phases posttransplant would be an important step toward the development of improved therapeutic approaches. The goal of this review is to outline recent studies regarding antibody production in general and specific studies that illustrate what is known about alloantibody production in sensitized patients. [source] Early and Limited Use of Tacrolimus to Avoid Rejection in an Alemtuzumab and Sirolimus Regimen for Kidney Transplantation: Clinical Results and Immune MonitoringAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009S. J. Knechtle Alemtuzumab induction with 60 days of tacrolimus treatment and continuous sirolimus treatment prevented acute rejection in nine of 10 consecutive renal allograft recipients. All patients are alive with a functioning kidney graft at 27,39 months of follow-up. Extensive immune monitoring was performed in all patients. Alloantibody detection, cytokine kinetics assay (CKA), and trans vivo delayed-type hypersensitivity (DTH) assay were performed every 6 months showing correlation with clinical evolution. Despite alloantibody presence in five patients, eight patients remain without the need for specific treatment and only sirolimus monotherapy in decreasing dosage. Four patients take only 1 mg sirolimus daily with levels of 3,4 ng/mL. One patient showed clinical signs of rejection at month 9 post-transplant, with slow increase in serum creatinine and histological signs of mixed cellular (endarteritis) and humoral rejection (C4d positivity in peritubular capillaries and donor-specific antibody (DSA)). In summary, the addition of tacrolimus therapy for 2 months to a steroid-free, alemtuzumab induction and sirolimus maintenance protocol limited the previously shown acute rejection development. Nevertheless, alloantibody was present in serum and/or C4d present on 1-year biopsy in half the patients. The combination of CKA and DSA monitoring or the performance of transvivo DTH correlated with immune status of the patients. [source] Pulmonary Capillaritis as a Manifestation of Acute Humoral Allograft Rejection Following Infant Lung TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009T. L. Astor Pulmonary capillaritis has been described in adult lung transplant recipients, but has not been previously reported in pediatric recipients. We report a case of posttransplant pulmonary capillaritis in an 8-month-old infant, and demonstrate evidence of C4d deposition and B-lymphocytes in the allograft, donor anti-HLA antibodies in the serum and a clinical and immunohistochemical response to anti-CD20 monoclonal antibody (rituximab) therapy. These findings strongly support the hypothesis that pulmonary capillaritis may represent a form of acute humoral rejection in the lung allograft that is less common than, and clinically and histologically distinct from, typical acute cellular rejection. [source] Proteasome Inhibition Causes Apoptosis of Normal Human Plasma Cells Preventing Alloantibody ProductionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009D. K. Perry Antibody production by normal plasma cells (PCs) against human leukocyte antigens (HLA) can be a major barrier to successful transplantation. We tested four reagents with possible activity against PCs (rituximab, polyclonal rabbit antithymocyte globulin (rATG), intravenous immunoglobulin (IVIG) and the proteasome inhibitor, bortezomib) to determine their ability to cause apoptosis of human bone marrow-derived PCs and subsequently block IgG secretion in vitro. IVIG, rituximab and rATG all failed to cause apoptosis of PCs and neither rituximab nor rATG blocked antibody production. In contrast, bortezomib treatment led to PC apoptosis and thereby blocked anti-HLA and antitetanus IgG secretion in vitro. Two patients treated with bortezomib for humoral rejection after allogeneic kidney transplantation demonstrated a transient decrease in bone marrow PCs in vivo and persistent alterations in alloantibody specificities. Total IgG levels were unchanged. We conclude that proteasome activity is important for PC longevity and its inhibition may lead to new techniques of controlling antibody production in vivo. [source] The Long-Term Prognosis of Renal Transplant in Patients With Systemic VasculitisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2007G. Moroni Little information is available about the long-term outcome of renal transplantation in patients with systemic vasculitis (SV). We compared the outcomes of 19 renal transplant recipients with SV with those of 38 controls matched for time of transplantation, age, gender and source of donor. The mean post-transplant follow-up was 58 ± 57 months for vasculitic patients and 61 ± 49 months for controls. The actuarial 10-year patient survival was 87% in vasculitic patients and 90% in controls, death-censored graft survival were 84% and 100%, respectively. The risks of acute and chronic rejection, and arterial hypertension were not significantly different between the two groups. Infection was significantly more frequent in vasculitic patients (74% vs. 34%; p = 0.01). Seven patients (36.8%) had a recurrence of vasculitis in mean 45 months after renal transplant (0.076/patients/year). After recurrence, one patient had an irreversible humoral rejection, another died from hemophagocytosis and another restarted dialysis 1 year later. Long-term patient and renal allograft survival in vasculitic patients was good. Although graft function recovered in most relapsers after reinforcement of immunosuppression, one patient died and two lost graft function. [source] Peritubular Capillary Damage in Acute Humoral Rejection: An Ultrastructural Study on Human Renal AllograftsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2005P. Lipták The ultrastructural features of peritubular capillary (PC) damage was studied in 12 kidney allografts with acute humoral rejection (AHR). AHR manifested in diffuse linear PC staining for C4d, and histology consistent with Banff grade III in 7 recipients and Banff grade II in 5. Allografts with acute tubular necrosis served as controls. First biopsies (post-transplantation day 16.2 ± 2.2): The intra-capillary exudate comprised monocytes (59%), polymorphonuclears (14%), lymphocytes (12%) and not otherwise specified mononuclears (15%). Three patterns of focal PC endothelial injury were observed: lysis, an increased rate of apoptosis and fragmentation. No correlation was found between the respective damage types and the inflammatory cell types or the Banff grades. Controls revealed endothelial swelling, detachment from basement membrane and fragmentation. Follow-up biopsies: Monocytes transformed into macrophages intra-luminally. The reparative changes comprised endothelial cytoplasmic protrusions, binucleated endothelial cells and capillary sprouts. Early transplant capillaropathy and transplant glomerulopathy were noted in 2 recipients. Literature data indicate that lysis is mediated by anti-HLA alloantibodies; apoptosis, demonstrated first in the present study, may be induced by non-HLA-type anti-endothelial antibodies. Fragmentation is caused by ischemia. Ongoing endothelial injury leads to transplant capillaropathy and transplant glomerulopathy, the characteristic lesions of chronic rejection. [source] Accommodation in ABO-Incompatible Kidney Allografts, a Novel Mechanism of Self-Protection Against Antibody-Mediated InjuryAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2003Walter D. Park To elucidate the mechanism of self-protection against anti-donor blood-group antibody known as accommodation, we studied 16 human ABO-incompatible living-donor kidney transplant recipients at 3 and 12 months post transplantation. Both circulating anti-blood-group antibody and the target blood-group antigen in the graft were demonstrable in all patients after transplantation. Thirteen of 16 grafts had normal renal function and histology, while three grafts with prior humoral rejection demonstrated significant glomerulopathy and thus did not meet the criterion for accommodation. Using microarrays, we compared five 1-year protocol ABO-compatible renal graft biopsies to four accommodated ABO-incompatible graft biopsies. Significant alterations in gene expression in 440 probe sets, including SMADs, protein tyrosine kinases, TNF-, and Mucin 1 were identified. We verified these changes in gene expression using RT-PCR and immunohistochemistry. Heme oxygenase-1, Bcl-2 and Bcl-xl were not increased in ABO-incompatible grafts at any time-point. We conclude that accommodation is always present in well-functioning, long-surviving ABO-incompatible kidney transplants. This self-protection against antibody-mediated damage may involve several novel mechanisms including the disruption of normal signal transduction, attenuation of cellular adhesion and the prevention of apoptosis. [source] Porcine Antigen Presenting Cells Produce Soluble Adjuvants That Stimulate B cells Within and Across the SpeciesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2003Nada Kanaan Interactions between porcine antigen presenting cells (pAPCs) and host lymphocytes may be important in cellular and humoral rejection of porcine organ xenografts. To investigate the role of pAPCs in the activation of xenogeneic lymphocytes, porcine bone marrow cells were stimulated using porcine GM-CSF with or without porcine IL-4 to generate populations of pAPCs that had phenotypic characteristics of myeloid dendritic cells. These bone marrow-derived pAPCs were weak stimulators of xenogeneic (mouse and human) T cells in vitro but induced primary B-cell proliferation and augmented CD40-induced B-cell proliferation. Inoculation of mice with small numbers of pAPCs resulted in localized expansion of lymph node B cells. The mitogenic effect on xenogeneic B cells could be reproduced by medium in which pAPCs had been cultured, implicating one or more soluble products. In blocking experiments IL-12, IL-6, and IL-10 were found not to contribute to the mitogenic effect of pAPC medium. In contrast, pIFN was found to be capable of augmenting CD40-induced proliferation of xenogeneic B-cell proliferation but did not act as a B-cell mitogen. We conclude that myeloid APCs from the pig produce soluble factors that are capable of acting as primary mitogens for xenogeneic B cells as well as augmenting additional B-cell activating stimuli. This direct interaction between porcine APCs and xenogeneic B cells may serve as an important adjuvant for the stimulation of humoral immunity to porcine xenografts. [source] C4d deposition on peritubular capillary (PTC) in the protocol biopsy of ABO-incompatible kidney transplantation under the treatment with anti-CD20 antibody and without splenectomyCLINICAL TRANSPLANTATION, Issue 2007Naofumi Imai Abstract:, For the desensitization of A/B antigens, we had developed and reported a new potent immunosuppressive treatment, which is the pre-prescription of anti-CD20 monoclonal antibody with mycophenolate mofetil and low-dose steroid. Using this kind of desensitization therapy, splenectomy is not required at the kidney transplantation. Complement C4d deposition on peritubular capillary (PTC) in graft biopsy has been reported as a relatively reliable marker for humoral rejection. However, the C4d deposition was often observed in the graft biopsy of ABO-incompatible kidney transplantation even with no rejection findings. The aim of this study was to examine the effect of this treatment on C4d deposition on PTC. Baseline and protocol graft biopsies obtained from 12 recipients of ABO incompatible kidney transplants were evaluated by light and immunofluorescence microscopy. To elucidate the involvement of classical and/or lectin pathway of complement cascades in C4d deposition, we examined the deposition of the initial activating proteins on PTC, IgG and IgM in the classical pathway and mannose-binding lectin (MBL), H-ficolin, L-ficolin, MBL-associated serine protease (MASP)-1 and MASP-2 in the lectin pathway. Three out of nine available baseline biopsy specimens showed diffuse C4d and IgM deposition on PTC. In the protocol biopsy, nine of 12 specimens revealed diffuse C4d deposition on PTC. Five of them had positive deposition of IgM and H-ficolin on PTC, whereas the other initial proteins were not detected in all specimens. Apart from one case, the histological findings of the protocol biopsies were normal or borderline changes. Our study suggested that although the new treatment with anti-CD20 antibody treatment and without splenectomy was clinically effective, it did not perfectly inhibit C4d deposition on PTC. It also confirmed the dual activation of both classical and lectin pathways in the process of C4d deposition on PTC in ABO-incompatible transplantation. [source] A case of acute vascular rejection after overseas deceased kidney transplantationCLINICAL TRANSPLANTATION, Issue 2007Tomokazu Shimizu Abstract:, A 54-yr-old Japanese male received overseas deceased kidney transplantation in January 2006. His allograft functioned immediately and he received immunosuppression with cyclosporine A (CyA), mycophenolate mofetil (MMF), and prednisone (PR). On day 24 after transplantation, he came back to Japan. His serum creatinine level (s-Cr) was 1.39 mg/dL at two months after transplantation when he was admitted into Toda Central General Hospital on March 2006, for follow-up his renal allograft. He had taken only two immunosuppressive drugs, MMF and PR, and had not taken CyA at that time. His serum creatinine gradually rose after hospitalization. Allograft biopsy performed on April 6, 2006, showed acute vascular rejection (Banff 97 acute/active cellular rejection Grade III), together with suspicious for acute humoral rejection (Banff 97 antibody-mediated rejection Grade II). After treatment of two courses of steroid pulses and five d of gusperimus, acute vascular rejection and acute humoral rejection were relieved, which had been proven by the third allograft biopsy. In conclusion, this was a case of acute vascular rejection after overseas deceased kidney transplantation, resulted from non-compliance with immunosuppressive therapy. [source] Peritubular capillary C4d deposition and renal outcome in post-transplant IgA nephropathyCLINICAL TRANSPLANTATION, Issue 2 2007Jung Choi Abstract:, Backgrounds:, Immunological staining of the transplanted kidney for C4d in peritubular capillaries (C4dPTC) has emerged as a useful method to detect antibody-mediated rejection in situ. In this retrospective study, we evaluated the prevalence of C4dPTC deposition in allograft renal biopsies diagnosed of IgA nephropathy (IgAN) and analysed its clinical significance. Method:, Sixty-six biopsy specimens of post-transplant IgAN, which were obtained to evaluate azotemia and/or heavy proteinuria, were examined by immunohistochemical staining of the paraffin sections with polyclonal antibody for C4d. Results:, C4d was stained positively in peritubular capillaries in 16 (24%) of the 66 cases. The C4dPTC -negative (n=50) and C4dPTC -positive groups (n=16) were not different in recipient gender, age, donor age, type of donor (living vs. cadaveric), interval from transplantation to graft biopsy (41.6± 21.8 vs. 48.3±26.1 months) and post-biopsy follow-up period (60.3±23.3 vs. 56.9±25.4 months). During the follow-up period, 12 of 50 (24%) although the incidence of graft failure was not different by the C4d deposition in peritubular capillaries, intervals from renal biopsy to graft failure tended to be shorter in C4dPTC -positive cases than C4dPTC -negative cases. In Kaplan,Meier analysis, the renal allograft function of the C4dPTC -positive group deteriorated more rapidly than that of the C4dPTC -negative group (p<0.05). Histologically, the C4dPTC -positive group had findings suggestive of acute cellular rejection more commonly than the C4dPTC -negative group (p<0.01). Conclusions:, Evidence of humoral rejection, as demonstrated by C4dPTC deposition, was concurrently present in significant portions of post-transplant IgAN biopsy specimens and was associated with more rapid deterioration of renal function. These results suggest that C4dPTC positivity needs to be determined at the time of biopsy even in cases of post-transplant glomerulonephritis and immunosuppression may need to be modified accordingly. [source] C4d in pediatric renal allograft biopsies: A marker for negative outcome in steroid-resistant rejectionPEDIATRIC TRANSPLANTATION, Issue 4 2006Regina Vargha Abstract:, Recently, deposition of C4d, reflecting complement activation via the classical pathway, has been established as marker of antibody-mediated rejection. As C4d can be detected in paraffin sections, it allows for retrospective analysis in populations with low case loads, such as in pediatric transplantation. In this study we re-evaluated consecutive renal transplant biopsies obtained since 1990 in 36 children (18 boys, 18 girls) who had received their allograft (nine living, 27 cadaveric) at an age of 10.12±4.4 yr. Clinical indications for biopsy were 16 acute steroid resistant rejections (ASRs), 11 chronic rejections and nine other diagnoses. Overall, C4d deposition was found in nine cases (25%), eight of them with diagnosed ASR. Six out of these eight allografts were lost during 36 months of clinical follow-up, a significantly higher rate than in C4d-negative biopsies (p<0.05). C4d status therefore turned out to be an excellent predictor for inferior graft survival following ASR. None of the other histopathologic markers were sensitive for humoral rejections. In conclusion, the high prevalence of C4d-positive staining in ASR demonstrates the importance of the humoral part of the immune system in pediatric transplantation. The worse outcome of C4d-positive rejections despite massive immunosuppressive therapy clearly indicates the need for innovative therapies in this high-risk population. [source] | ||||||||||