Multiple Episodes Of Acute Rejection Research Articles

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation.

The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study was performed on six patients after hand transplantation. The control group consisted of: 12 kidney transplant recipients and 12 healthy volunteers. The following non-HLA antibodies were tested: antibody against angiotensin II type 1 receptor (AT1R-Ab), antibody against endothelin-1 type-A-receptor (ETAR-Ab), antibody against protease-activated receptor 1 (PAR-1-Ab) and anti-VEGF-A antibody (VEGF-A-Ab). Chosen proinflammatory cytokines (Il-1, IL-6, IFNγ) were used to evaluate the post-transplant humoral response. Laboratory markers of endothelial activation (VEGF, sICAM, vWF) were used to assess potential vasculopathy. The patient with the highest number of acute rejections had both positive non-HLA antibodies: AT1R-Ab and ETAR-Ab. The same patient had the highest VEGF-A-Ab and very high PAR1-Ab. All patients after hand transplantation had high levels of laboratory markers of endothelial activation. The existence of non-HLA antibodies together with multiple acute rejections observed in patient after hand transplantation should stimulate to look for potential role of non-HLA antibodies in humoral injury in vascular composite allotransplantation.

Recurrent graft failure secondary to portal vein steal syndrome: a case report with an unusual indication for a third liver transplant

BackgroundPortal vein shunt is common in chronic hepatic diseases and after a liver transplant. Ensuring a satisfactory portal flow is essential to support a rapid liver recovery, of paramount importance to meet the recipient’s metabolic needs.Case presentationWe report the case of a 32-year-old female undergoing a third liver transplant due to recurrence of graft failure secondary to portosystemic shunting. The patient, affected with biliary atresia, was first transplanted in 2009 with a right split liver graft. The clinical course was complicated by biliary stenosis of the Roux-en-Y anastomosis and multiple episodes of acute rejection treated with steroid boluses, plastic dilation of the biliary anastomosis, and biliary catheter placement. Unfortunately, in 2017 a liver biopsy showed an autoimmunity with histological evidence of ANA 1:80 (granular and nucleolar pattern). This was a contributing factor of liver function impairment, leading to the need to perform a second liver transplant, complicated by an acute rejection, with only a partial response to steroid therapy. Due to the further worsening of the liver function (MELD: 40, Child–Pugh: C11), the patient was relisted for a liver transplant. After five days, she received her third liver transplant, with an entire graft of an AB0 identical group. Intraoperative exploration revealed multiple collaterals and large splenocaval shunts, with a significant alteration of the portal flow and hypertension, isolated and closed with a vascular stapler to restore the graft's regular portal vein flow.ConclusionsIn patients listed for a liver transplant, portal steal syndrome should be identified prior to the transplant. Our recommendation is to consider intraoperative or perioperative closure of the portal collateral varices.

Case Report: Malakoplakia Developing in the Graft Colon Post Intestinal Transplant

Abstract Casestudy Malakoplakia is a rare chronic granulomatous disease thought to be caused by a macrophage bactericidal defect and most commonly affecting the genitourinary tract. Most cases are associated with chronic infections or immunosuppression, with most transplant related cases observed after renal transplantation. Results A male in his thirties developed short gut syndrome secondary to injuries and subsequently underwent a small and large bowel transplant and was treated with immunosuppressive medications. He developed multiple episodes of acute rejection and multiple infectious foci, including a peri-rectal fluid accumulation growing Escherichia Coli, bacteremia with Klebisella oxytica, and Epstein Barr Virus viremia. Functional imaging revealed increased activity in mesenteric lymph nodes and in the peri-rectal fluid accumulation. On endoscopy, a rectal ulcer associated with mucosal protuberance was noted and tissue was obtained for pathologic diagnosis. Histologic examination revealed mucosal infiltration by numerous macrophages with abundant granular cytoplasm. Michaelis-Gutmann bodies (considered pathognomonic for malakoplakia) were identified showing PAS and Von- Kossa positivity. Acid fast stain was negative. These findings supported the diagnosis of malakoplakia. Other differential diagnoses were considered, including post-transplant lymphoproliferative disorder, neoplasia, infection with mycobacterial or fungal species, and secondary hemophagocytic lymphohistiocytosis syndrome. These were excluded based on the characteristic histologic findings. Given the diagnosis, treatment with oral antibiotics was attempted. Follow up biopsies revealed disease persistence and the patient was transitioned to a prolonged course of intravenous antibiotics and bethanechol, with eventual histologic response. Unfortunately, due to stenosis and adhesions that developed secondary to the episodes of acute rejection, the patient eventually underwent graft explanation. Conclusion Our case highlights the risk factor milieu encountered in intestinal transplant patients and the prolonged treatment often required to treat malakoplakia. Additionally, malakoplakia constitutes an unusual consideration in intestinal transplant patients and prompt diagnosis is required to direct proper management of these patients.

2402 A Rare Case of IPEX Syndrome With Hepatic Complications

INTRODUCTION: Immunodysregulation, polyendocrinopathy and enteropathy X-linked (IPEX) Syndrome is a rare autoimmune illness affecting only males starting in the early few months of life. It can be associated with autoimmune hepatitis among other systemic ailments and ultimate treatment is immunosuppression or bone marrow transplant. We present a case of undiagnosed IPEX Syndrome leading to liver failure requiring eventual liver transplantation. CASE DESCRIPTION/METHODS: A 19 year-old male patient had undergone a liver transplant at age 2 for suspected autoimmune hepatitis resulting in acute liver failure. No specific cause was identified at time of diagnosis. He remained on chronic immunosuppression thereafter, eventually progressing to chronic active autoimmune hepatitis in the transplanted liver. He was diagnosed with IPEX Syndrome at age 16, for which he underwent a bone marrow transplant. He presented to the hospital with neutropenia, and hepatology was consulted for liver transplant rejection in light of mild transaminitis. On admission, vital signs were normal and pertinent labs include: AST/ALT 50/74 units/L, Alkaline Phosphatase 811 IU/L, Albumin 3.4 g/dL, WBC 0.6 × 109 cells/L. He reportedly had multiple episodes of acute rejection in the past which were treated with steroids. Chronically, he was on mycophenolate mofetil, tacrolimus, and prednisone. His liver biopsy did not show evidence of acute rejection, but suggested chronic rejection and liver fibrosis. A prior liver biopsy had suggested autoimmune hepatitis, but no evidence of a flare on current biopsy. He was continued on his current immunosuppression regimen, and he was subsequently discharged home. DISCUSSION: Due to its rarity, incidence of IPEX syndrome is not entirely known, but is estimated to be 1 in 1,609,490. Generally, it is diagnosed in infancy and is often fatal. Our case is unique as the diagnosis was missed for more than a decade during which period the patient had even received a liver transplant for autoimmune hepatitis. Autoimmune hepatitis reportedly occurs in 20% of patients with IPEX Syndrome. There are currently no reports of liver failure requiring liver transplant in such scenarios. The fact that our patient developed recurrent autoimmune hepatitis in the transplanted liver highlights the underlying defect in his genetic disorder. This case should serve as a reminder to clinicians to consider IPEX syndrome in the differential for early onset autoimmune hepatitis, as early diagnosis could reduce significant morbidity.

Late cytomegalovirus infection in children: High incidence of allograft rejection and hepatitis in donor negative and seropositive liver transplant recipients.

The complications and outcome associated with late CMV infection and disease on the graft are poorly characterized in PLT recipients. We studied the overall incidence, risk factors, and outcome of late CMV infection and disease (infection 6months after transplant) in 180 PLT recipients admitted between 2008 and 2011 at the King's College Hospital. Antiviral prophylaxis of intravenous ganciclovir was given only to the D+R- group starting at day 7 post-transplant. The remaining groups (D-R+, D+R+, and D-R-) received pre-emptive therapy when they have CMV viremia above cut-off value and treatment for symptomatic CMV infection. The overall incidence of late CMV infection and disease was 9.4% (19/180) and 14.5% (19/130) in D+R-, D-R+, D+R- groups. The D-R+ group had the highest incidence of hepatitis (37.5%) and significantly increased incidence of CMV disease, and single and multiple acute rejection episodes when compared to the D+R- group, which received prophylaxis. The late CMV infection and disease in pediatric LT recipients was comparable to adult LT recipients despite variable duration of antiviral prophylaxis. Our results show that D-R+group had highest rate of hepatitis and rejection episodes, associated with high morbidity, and should be considered for antiviral prophylaxis.

De novo development of circulating anti-endothelial cell antibodies rather than pre-existing antibodies is associated with post-transplant allograft rejection

Anti-endothelial cell antibodies (AECAs) are thought to be involved in the development of renal allograft rejection. To explore this further, we determine whether AECAs play a role both in predicting the incidence of allograft rejection and long-term outcomes by analysis of serum samples from 226 renal allograft recipients for AECAs pre- and post-transplant. Surprisingly, the presence of pre-existing AECAs was not associated with either an increased risk of rejection or a detrimental impact on recipient/graft survival. Subsequent de novo AECAs, however, were associated with a significantly increased risk of early acute rejection. Moreover, these rejections tended to be more severe with a significantly increased incidence of both steroid-resistant and multiple episodes of acute rejection. The acute rejections associated with de novo AECAs did not correlate with C4d deposition at the time of renal biopsy, but did demonstrate an association with the presence of glomerulitis and peritubular capillary inflammation. Significantly more patients with de novo AECAs developed graft dysfunction. Thus, our prospective study suggests the emergence of de novo AECAs is associated with transplant rejection that may lead to allograft dysfunction.

Gastroesophageal Reflux Disease Is Associated With an Increased Rate of Acute Rejection in Lung Transplant Allografts

Purpose Gastric fundoplication (GF) for gastroesophageal reflux disease (GERD) may protect against the progression of chronic rejection in lung transplant (LT) recipients. However, the association of GERD with acute rejection episodes (ARE) is uncertain. This study sought to identify if ARE were linked to GERD in LT patients. Methods This single-center retrospective observational study, of patients transplanted from January 1, 2000, to January 31, 2009, correlated results of pH probe testing for GERD with ARE (≥International Society for Heart and Lung Transplantation A1 or B1). We compared the rates of ARE among patients with GERD (DeMeester Score > 14.7) versus without GERD as number of ARE per 1,000 patient-days after LT. Patients undergoing GF prior to LT were excluded. Results The analysis included 60 LT subjects and 9,249 patient-days: 33 with GERD versus 27 without GERD. We observed 51 ARE among 60 LT recipients. The rate of ARE was highest among patients with GERD: 8.49 versus 2.58, an incidence density ratio (IDR) of 3.29 ( P = .00016). Upon multivariate negative binomial regression modeling, only GERD was associated with ARE (IDR 2.15; P = .009). Furthermore, GERD was associated with multiple ARE (36.4% vs 0%; P < .0001) and earlier onset compared with patients without GERD: ARE proportion at 2 months was 0.55 versus 0.26 P = .004). Conclusion In LT recipients, GERD was associated with a higher rate, multiple events, and earlier onset of ARE. The efficacy of GF to reduce ARE among patients with GERD needs further evaluation.

Composite Tissue Vasculopathy and Degeneration Following Multiple Episodes of Acute Rejection in Reconstructive Transplantation

Transplant vasculopathy has not been systematically investigated in composite tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs) on long-term graft outcomes in reconstructive transplantation remains unknown. This study in a rat hind-limb allotransplantation model systematically analyzes vasculopathy and tissue-specific pathological changes secondary to multiple AR episodes. LEW rats were transplanted with BN rat hind limbs and treated as follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3 (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group 3 animals demonstrated significant vascular lesions along with skin and muscle atrophy, upregulation of profibrotic gene expression and fibrosis when compared to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas muscle atrophy with macrophage infiltration was seen early, after only a few AR episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue-specific pathology in CTA. This is the first evidence of 'composite tissue vasculopathy and degeneration (CTVD)' in CTA.

Investigation of Antibody-Mediated Rejection in Composite Tissue Allotransplantation in a Rat Limb Transplant Model

Background Despite the widely accepted implication of antidonor antibodies and complement in solid organ transplantation, their role in reconstructive allotransplantation is not clear. The aim of this study was to analyze the humoral immune response using a rat orthotopic limb transplantation model. Methods We used the Brown Norway to Lewis rat orthotopic hind-limb transplant model: Group 1, isografts; group 2, allografts with daily continuous cyclosporine treatment to prevent acute rejection; and group 3, allografts undergoing multiple episodes of acute rejection. Samples were taken at 30, 60, and 90 days. Serum was analyzed by FACS for antidonor antibodies. Tissue deposition of antibodies and complement was investigated by immunofluorescence. Results By day 90, animals in group 3 had undergone 19 (±3.2) acute rejection episodes. There was no difference in the occurrence of serum antidonor antibodies between the three groups at any time point. However, at 90 days, anti–third-party antibodies were significantly greater among group 3. There was no difference in antibody or complement deposition in muscles between the 3 groups. Conclusion Despite the increased antibody against a third party after multiple rejection episodes in this animal model, there was no clear evidence of an antibody-mediated alloresponse in limb transplantation.

Hepatic parenchymal changes and histologic eosinophilia as predictors of subsequent acute liver allograft rejection

During the first episode of acute cellular rejection (ACR) after liver transplantation, centrilobular changes in liver biopsy specimens may be possible indicators of subsequent episodes of ACR, early chronic rejection, or acute graft loss. The purpose of this study was to identify differences between the histopathological findings in liver biopsy specimens obtained during the first rejection episode in patients who subsequently developed further episodes of ACR and those who did not. The histopathological findings in 22 patients who had a single episode of acute rejection (group 1) were compared with those in 23 patients who had multiple episodes of acute rejection (group 2). Only the first liver biopsy samples of the latter group were taken into consideration. We assessed the predictive value of centrilobular necrosis, central vein endothelialitis, pericentral inflammation, hepatocellular ballooning, cholestasis, hepatocellular apoptosis, lobular inflammation, the degree of portal eosinophilia, and characteristic portal tract features in poor responders to antirejection treatment. The time to the first episode of ACR and the rejection activity index were similar in patients in both groups. Hepatocellular apoptosis, hepatocellular ballooning, and central vein endothelialitis were common features of both groups. The incidences of pericentral inflammation, centrilobular necrosis, and portal eosinophilia were significantly higher in patients in group 2 than in those in group 1 (P < 0.05). Patients with pericentral inflammation, centrilobular necrosis, and marked portal eosinophilia during an initial episode of acute rejection may be more likely to develop subsequent episodes of ACR.

Peritubular capillary C4d staining in late acute renal allograft rejection - is it relevant?

In the early post-transplant period, renal allograft rejection with diffuse peritubular capillary (PTC) C4d deposition predicts poor graft survival. In the late post-transplant setting, that is, one or more yr after transplantation, the implication of diffuse PTC C4d deposition is still a topic of debate. The purpose of our study was to see if diffuse PTC C4d deposition, in late acute rejection (LAR), occurring more than one yr post-transplant, has any impact on graft survival and function. We selected cases, both cadaveric as well as living donor renal transplant recipients, in whom acute rejection with PTC C4d deposition was first detected after the first year post-transplant. Recipients with multiple acute rejection episodes during the first year post-transplant were excluded from the study. The first biopsy diagnosed with LAR was considered the index biopsy (n = 40). We formed two groups: group 1, C4d-positive LAR (n = 20), and group 2, C4d-negative LAR (n = 20). Groups were matched for maintenance and post-rejection immunosuppressive therapy, baseline serum creatinine levels before the time of the index biopsy, time from transplant to index biopsy, as well as chronic allograft damage index (CADI) score in the index biopsies. We compared the rate of graft loss, and the graft function of the surviving grafts at the end of the study period, as well as histologic parameters in the index biopsy specimens between the two groups. The mean follow-up period was 20 months. No significant differences in the rate of graft loss or graft function were found between groups 1 and 2 at the end of the follow-up period. Histologically, PTC margination and transplant glomerulopathy were more common in the C4d-positive group, and this difference was statistically significant. There was no statistically significant difference in the degree of plasma cell infiltrates. Unlike in the acute setting, the presence or absence of PTC C4d staining in renal allografts with LAR may not have a predictive value regarding graft outcome.

Risk factors for rising creatinine in renal allografts with 1 and 3 yr survival

Determining factors associated with negative slope of inverse creatinine vs. time (1/Cr vs. t) may help prevent a decline in renal allograft function. A total of 1389 adult recipients of primary renal transplants were divided into quartiles based on the slope of 1/Cr vs. t calculated from 6 and 12 months post transplant. A multivariate analysis of risk factors for being in the worst vs. best quartile employed these variables: donor source, HLA mismatch, recipient age, donor age, panel-reactive antibody (PRA), acute rejection (AR), 3-month cyclosporin A (CsA) level, 1-yr CsA level and acute tubular necrosis. Two separate analyses compared risk factors in patients with 1 and 3 yr survival, respectively. In recipients with > or = 1 yr graft survival, high PRA and AR were associated with negative slopes of 1/Cr vs. t. For those with > or = 3 yr graft survival, both AR and 3-month CsA level > 150 ng/mL were significant risk factors, using both 6- and 12-month slopes. Stratification of AR showed 1 AR episode > or = 6 months and multiple AR episodes carried significant risk for negative slopes. Optimization of allograft function invokes a conundrum between the needs to avoid both AR and high early CsA levels. We support a policy of carefully balancing these two risks.

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome with Renal Failure: Impact of Posttransplant Immunosuppression on Disease Activity

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the gene AIRE (autoimmune regulator). APECED affects mainly endocrine organs resulting in hypoparathyroidism, adrenocortical failure, diabetes mellitus, hypogonadism, and hypothyroidism. Nonendocrine organ manifestations are autoimmune hepatitis, vitiligo, pernicious anemia, exocrine pancreatic insufficiency, and alopecia. APECED's first manifestation generally is mucocutaneous candidiasis presumably related to T cell dysfunction. A 5-yr-old Iranian girl presented first with pernicious anemia, exocrine pancreatic insufficiency, and nail candidiasis. She had renal dysfunction due to chronic interstitial nephritis (CIN), which progressed to end-stage renal failure. She was transplanted 1 yr later. Common causes of CIN were excluded. APECED was suspected first because she developed progressively hypoparathyroidism, adrenocortical failure, glucose intolerance, and hypothyroidism. Genetic analysis revealed a large homozygous deletion (g.424_2157del1734), spanning exons 2-4, in the AIRE gene. The predicted protein, if it is produced, has only 44 amino acids (exon 1) in common with the wild-type protein. Immunosuppression after the first renal transplant included prednisone, azathioprine, and cyclosporine A. Multiple acute rejection episodes occurred. Chronic rejection resulted in lost graft and she was retransplanted 2 yr later. Surprisingly, all APECED-related symptoms including candidiasis and autoantibody levels decreased, presumably due to the reinforced immunosuppression (tacrolimus, mycophenolate mofetil, prednisone). This is the first report of an APECED patient with CIN resulting in end-stage renal failure. Clinical and biological improvement was observed under posttransplant multidrug immunosuppression including tacrolimus and mycophenolate mofetil.

Antithymocyte Globulin Induction Therapy in Hepatitis C–Positive Liver Transplant Recipients

It is unclear whether antithymocyte globulin (ATG) induction therapy in hepatitis C-positive (HCV-positive) liver transplant recipients influences the risk of developing recurrent HCV disease. Multiple acute rejection episodes and high-dose steroids and/or OKT3 used to treat acute rejection increase the risk of graft loss from HCV. We studied the impact of ATG induction on graft and patient survival in HCV-positive liver transplants performed since 1990. Recipients who died or lost their grafts within 1 month of transplantation were excluded. Second, third, and fourth grafts were excluded, as were patients with stage III or IV hepatocellular carcinoma. There were 443 cadaveric liver transplants in adult recipients, of whom 142 (32%) were HCV positive. The incidence of biopsy-proven acute rejection was less in patients who received ATG induction, 34.2% (ATG induction) versus 66.6% (no ATG induction) (P<or=.01). ATG induction did not influence the risk of graft loss from HCV-related disease (P=.75). When only HCV-related graft loss was considered, 10-year graft survival for HCV-positive recipients was 74% (ATG induction) versus 68.2% (no ATG induction). Whether ATG induction was given or not had no significant impact on either overall graft survival (P=.39) or patient survival (P=.11) in HCV-positive recipients.

Outcomes of Patients With Rejection Post–Polyomavirus Nephropathy

Introduction We sought to determine the effects of rejection in renal transplant recipients with polyomavirus nephropathy (PVN). Methods SCr, biopsy findings, BKV serum and urine loads (Taqman PCR), and BKV antibody titers (HA inhibition assay) were analyzed by two-sample median tests and z tests in 11 patients with median follow-up of 7.3 (2.0 to 31.5) months post-PVN. All patients underwent immunosuppression reduction (ISR) as PVN treatment. Results Post-PVN, 3 (27%) patients had five rejection episodes, with 80% being mild. Median time to rejection was 18 (2 to 60) weeks. One hundred percent of patients who experienced post-PVN rejection also experienced rejection pre-PVN. Rejection episode treatments consisted of: none in one, increased tacrolimus in two, IVIG in one, IVIG and increased tacrolimus in one. Median viral loads in patients with post-PVN rejection versus those without rejection were not different in serum (2.01 × 10 4 vs 9.00 × 10 4 BKV copies/mL; P = .22) or urine (5.37 × 10 5 vs 8.93 × 10 6 BKV copies/mL; P = .28). Median BKV antibody titers were slightly lower (16384 vs 32768 HA units; P = .02) and median SCr values were significantly higher (2.7 vs 1.9 mg/dL, P = .0003) in patients who had experienced post-PVN rejection. Graft losses occurred in one rejection-free patient (chronic allograft nephropathy) and in one patient who experienced multiple acute rejection episodes, humoral rejection, and worsening PVN. Conclusions Patients who experience rejection prior to PVN are at high risk of developing rejection post-ISR and post-PVN; however, low graft loss rates may still be achieved.

VIRAL LOAD MONITORING IN PATIENTS WITH POLYOMAVIRUS NEPHROPATHY WHO HAVE BEEN TREATED FOR REJECTION EPISODES

P823 Aims: Rejection occurring after reduction of immunosuppression for treatment of polyomavirus nephropathy (PVN) is a difficult clinical problem, as an increase in immunosuppression could result in a worsening of PVN. Recent anecdotal literature has suggested that treatment of rejection episodes followed by a rapid reduction of immunosuppression may prevent a relapse of PVN. The aim of this study was to determine the effects of a transient increase in immunosuppression for the treatment of acute rejection on viral load monitoring parameters in renal transplant recipients diagnosed with PVN. Methods: Four patients experienced six rejection episodes post PVN. BKV serum and urine viral loads were analyzed by Taqman PCR and anti-BKV antibody titers (ab) were analyzed by hemagglutination assay at the time of rejection, and at 8 and 24 weeks post rejection episode. Results: Four patients experienced six rejection episodes (multiple episodes in two patients) post PVN. Median time to acute rejection post PVN was 18 (2-60) weeks. Four of the rejections were mild, 1 was moderate and one patient developed humoral rejection after multiple acute cellular rejection episodes. Rejection treatment consisted of: none in 1, increased tacrolimus in 2, IVIG and increased tacrolimus in 1, leflunomide in 1 and IVIG alone in 1. Median BKV serum and urine viral loads did not deteriorate following the treatment of rejection (BKV serum viral load 5.04 x 10 4 at rejection vs 7.70 x 10 2 copies/mL post-rejection) and (BKV urine viral load 1.22 x 10 6 at rejection vs 1.52 x 10 4 copies/mL post-rejection). Median anti-BKV antibody titers were higher in patients post rejection (8192 at rejection vs 32968 HA units post rejection) and median serum creatinine values were not worse post rejection treatment followed by a reduction of immunosuppression (median serum creatinine at rejection 2.6 vs 2.1 mg/dL post rejection) Of patients who experienced post PVN rejection episodes, graft loss occurred in one patient (25%) who experienced multiple acute rejection episodes followed by humoral rejection and worsening PVN. Conclusions: 1) Transient increases in immunosuppression for the successful treatment of acute rejection episodes, in patients with PVN does not result in an increase in BKV viral loads. 2) Graft loss occurred only in 1 out of 4 patients experiencing rejection following diagnosis of PVN 3) Our results suggest that transient increases in immunosuppression for the treatment of rejection episodes in patients with PVN is indicated for the optimal management of these complex patients.

Transplant: immunology and treatment of rejection

Transplant: immunology and treatment of rejection

C3D deposition in peritubular capillaries indicates a variant of acute renal allograft rejection characterized by a worse clinical outcome.

C4d deposition in peritubular capillaries (PTCs) is a sign of humoral renal allograft rejection and an independent predictor of graft survival. Few investigators have focused on the meaning of capillary C3 deposition in rejecting grafts. Because C3 production can result from both classic and alternative pathway activation of the complement cascade, it is not clear whether C3 deposition indicates a distinct entity of acute rejection (AR) or merely represents a separate form of C4d-positive AR. We examined the deposition of C3d in the PTCs of recipients with AR in the first year posttransplantation (n=30). Clinical outcome variables and histology were compared with C3d-negative control patients (n=82). C3d-positive patients demonstrated more frequent preexisting T-cell antibodies (57%) and more re-transplants (37%), and they received more blood transfusions (mean 10.3 units). C3d-positive patients experienced more frequent multiple AR episodes (57%) and delayed graft function (36.7%). All nine C3d-positive recipients screened for posttransplantation donor-specific human leukocyte antigen antibodies demonstrated positive results. Graft failure occurred in 23% of C3d-positive recipients (7.3% in the control group) (P=0.03). C3d-positive biopsies showed significantly less tubulitis (P=0.03), whereas congestive PTCs with intraluminal accumulation of polymorphonuclear leukocytes were conspicuous. Thrombi, fibrinoid necrosis, and acute tubular necrosis were not more pronounced. In 19% of rejection biopsies, C3d deposition in PTCs was present without C4d deposition. In the remaining biopsies, C3d and C4d deposition was found simultaneously. The deposition of complement factor C3d in PTCs indicates a variant type of AR characterized by a worse clinical outcome.

THE SPECTRUM OF COMPLICATIONS OF IMMUNOSUPPRESSION

Brenner, Michael J. MD; Tung, Thomas H. MD; Jensen, John N. MD; Mackinnon, Susan E. MD Author Information

Rejection is reduced in thoracic organ recipients when transplanted in the first year of life

Background: Infant heart transplant recipients have been reported to have decreased rates of rejection when clinical criteria are used for diagnosis. This study compares the rates of acute episodes of rejection in heart and lung transplant recipients transplanted in the first year of life to those of older recipients utilizing pathologic criteria. Methods: Records of 100 consecutive lung transplant recipients (cystic fibrosis patients excluded) and 107 consecutive heart transplant recipients were reviewed with respect to: time to first rejection; total number; single versus multiple; and early (<90 days) versus late (>180 days) biopsy-proven rejection episodes. Rejection was defined as ISHLT biopsy Grade 3A or A2 for heart and lung transplant recipients, respectively. Biopsy and immunosuppression protocols were similar between groups. Results: Kaplan–Meier analysis for freedom from rejection showed infant heart recipients were more often rejection-free ( p = 0.004) as were infant lung recipients ( p = 0.0001). Multivariate analysis revealed age at transplant as the most significant factor in predicting time to first rejection (age <1 year: risk ratio 0.19 [0.068–0.54] for lung transplant recipients and risk ratio 0.46 [0.27–0.78] for heart transplant recipients). Early rejection episodes occurred with less frequency in both the infant heart (19 of 63 [30%] versus 24 of 44 [50%]; p = 0.016) and lung (3 of 26 [12%] versus 63 of 74 [85%]; p = 0.001) groups. Late episodes of rejection were also less frequent in infant heart (4 of 53 [8%] versus 10 of 36 [28%], p = 0.016) and lung (0 of 23 [0%] versus 29 of 65 [45%]; p = 0.001) recipients. Multiple (≥2) rejection episodes occurred less in infant heart (4 of 63 [6%] versus 9 of 41 [22%]; p = 0.037) and lung recipients (0 of 26 [0%] versus 17 of 74 [23%]; p = 0.003). Conclusions: These results demonstrate that age of <1 at time of thoracic transplantation confers significant protection from early, late and multiple episodes of acute rejection, as well as significantly greater freedom from rejection and time to first rejection.