Nondonor-specific Antibodies Research Articles

260.11: Impact of HLA donor specific antibody vs non-donor specific antibodies by single antigen bead method in predicting outcome of living related renal allograft recipients.

260.11: Impact of HLA donor specific antibody vs non-donor specific antibodies by single antigen bead method in predicting outcome of living related renal allograft recipients.

Both donor specific and non-donor specific HLA antibodies reduced in recipients post simultaneous liver/kidney transplant

It has been suggested that the liver allograft can protect the kidney allograft from antibody mediated rejection in simultaneous liver/kidney transplant (SLK) recipients by reducing preexisting donor specific antibodies (DSA) via adsorption of DSA by the liver allograft. Recently, the SLK allocation system was altered to provide a kidney safety net to those who do not recover native kidney function after liver transplant. However, the kidney transplant under the safety net creates a theoretical challenge for sensitized patients as the liver graft may not be able to adsorb human leukocyte antigen (HLA) antibodies against the kidney under the safety net because the liver and kidney grafts are from different donors and may carry different HLA antigens. This prompts us to examine levels of non-donor specific HLA antibodies in SLK recipients in our hospital. We found that levels of both DSA and non-DSA decreased post SLK transplant. The presence of preexisting DSA was also not associated with kidney graft survival and antibody mediated rejection in SLK recipients. Our results indicate that the liver transplant can reduce non-DSA, which may increase the pool of compatible kidneys offered under the safety net program for sensitized patients.

The allograft injury marker CXCL9 determines prognosis of anti-HLA antibodies after lung transplantation

Despite the common detection of non-donor specific anti-HLA antibodies (non-DSAs) after lung transplantation, their clinical significance remains unclear. In this retrospective single-center cohort study of 325lung transplant recipients, we evaluated the association between donor-specific HLA antibodies (DSAs) and non-DSAs with subsequent CLAD development. DSAs were detected in 30% of recipients and were associated with increased CLAD risk, with higher HRs for both de novo and high MFI (>5000) DSAs. Non-DSAs were detected in 56% of recipients, and 85% of DSA positive tests had concurrent non-DSAs. In general, non-DSAs did not increase CLAD risk in multivariable models accounting for DSAs. However, non-DSAs in conjunction with high BAL CXCL9levels were associated with increased CLAD risk. Multivariable proportional hazards models demonstrate the importance of the HLA antibody-CXCL9 interaction: CLAD risk increases when HLA antibodies (both DSAs and non-DSAs) are detected in conjunction with high CXCL9. Conversely, CLAD risk is not increased when HLA antibodies are detected with low CXCL9. This study supports the potential utility of BAL CXCL9measurement as a biomarker to risk stratify HLA antibodies for future CLAD. The ability to discriminate between high versus low-risk HLA antibodies may improve management by allowing for guided treatment decisions.

Non-donor specific anti-human leukocyte antigen (HLA) antibodies are not associated with poor outcome in hematopoietic stem cell transplant recipients

Testing for anti-human leukocyte antigen (HLA) antibodies has now become standard practice in allogeneic hematopoietic stem cell transplantation (HSCT), and anti-HLA antibodies (both donor specific and non-donor specific) are being identified and have many potential consequences. Most studies suggest that donor-specific HLA antibodies lead to adverse outcomes, though little is reported on non-donor specific anti-HLA antibodies. We present the results of a retrospective cohort analysis of 157 patients who received HSCT at the University of Rochester over a period of four years. We identified 45 patients (28.7%) who had detectable anti-HLA antibodies, while only one patient (0.6%) had donor-specific anti-HLA antibodies. Patients with prior pregnancies and multiple transfusions were at increased risk to develop antibodies. In our cohort, the presence of non-donor specific anti-HLA antibodies did not significantly impact overall survival, progression free survival, graft failure, or transplant-related mortality.

The incidence and clinical relevance of anti-HLA and/or MICA antibodies in patients with long-term survival renal allo-grafts

The purpose of this study was to analyze the incidence and clinical relevance of anti-HLA and/or MICA antibodies in renal allo-grafts transplant recipients with long-term renal survival (> 5 years). This retrospective study collected post-transplant serum samples from a total of 110 patients which were used to detect the incidence of anti-HLA and/or MICA antibodies as well as anti-HLA donor specific antibodies. Among these 110 patients, 72 patients had antibodies against HLA and/or MICA at the time of test, 61 had only anti-HLA antibodies, 31 had anti-MICA antibodies, and 38 were antibody negative. There was no difference in the number of patients developing antibodies against non-donor specific antibodies, donor specific antibodies, Class I donor specific antibodies, Class II donor specific antibodies or MICA antibodies between normal function group (serum creatinine level < 2.0 mg/dL) and dysfunction group (serum creatinine level > 2.0 mg/dL). For the serum creatinine level, estimated glomerular filtration rate and blood urea nitrogen level, patients with different antibodies were not statistically different to antibody-negative patients. Cox regression analysis showed that the type of transplantation and HLA mismatch number were significant negative risk factors for the development of anti-HLA (P < 0.05). Our results suggested that the anti-HLA antibody status has little impact on the renal graft function in the long-term survival allo-graft renal recipients.

Impact on mid-term kidney graft outcomes of pretransplant anti-HLA antibodies detected by solid-phase assays: Do donor-specific antibodies tell the whole story?

The detrimental impact of preformed anti-HLA donor-specific antibodies (DSA) is well defined, contrarily to non-donor-specific antibodies (NDSA). We sought to evaluate their clinical impact in a cohort of 724 kidney graft recipients in whom anti-HLA antibodies were thoroughly screened and identified in pre-transplant sera by solid-phase assays. NDSA or DSA were detected in 100 (13.8%) and 47 (6.5%) recipients respectively, while 577 (79.7%) were non-allosensitized (NaS). Incidence of antibody-mediated rejection at 1-year was 0.7%, 4.0% and 25.5% in NaS, NDSA and DSA patients, respectively (NaS vs. NDSA P=0.004; NaS vs. DSA P<0.001; NDSA vs. DSA P<0.001). Graft survival was lowest in DSA (78.7%), followed by NDSA (88.0%) and NaS (93.8%) recipients (NaS vs. NDSA P=0.015; NaS vs. DSA P<0.001; NDSA vs. DSA P=0.378). Multivariable competing risk analysis confirmed both NDSA (sHR=2.19; P=0.025) and DSA (sHR=2.87; P=0.012) as significant predictors of graft failure. The negative effect of NDSA and DSA on graft survival was significant in patients receiving no induction (P=0.019) or an anti-IL-2 receptor antibody (P<0.001), but not in those receiving anti-thymocyte globulin (P=0.852). The recognition of the immunological risk associated with preformed DSA but also NDSA have important implications in patients’ risk stratification, and may impact clinical decisions at transplant.

Self-antigens and rejection: a proteomic analysis.

Allo- and autoantibodies have been found to play important roles in both acute and chronic allograft rejection in organ transplantation, although only recently have non-human leukocyte antigen (non-HLA), nondonor-specific antibodies been given a more in-depth treatment. This review summarizes recent reports about investigations and proteomic approaches to identify self-antigens and corresponding autoantibodies that are associated with acute and chronic allograft rejection. Finally, we discuss the insights gained from these, challenges, and future prospects. Significant discoveries have been made regarding the presence and role of autoantibodies and alloantibodies, both those formed pretransplant and posttransplant, in acute and chronic rejection. These discoveries are made possible because of the publication of the human genome and subsequent development in the ability of expression and analysis of human proteome. Antibodies play a critical role in survival and dysfunction of a transplanted kidney. Even though HLA antibodies have been given the majority of the scientific community's attention for the past few decades, antibodies against autoantigens and that of non-HLA origin are gaining attention. Recent publications have identified novel self-antigens that are associated with acute and chronic rejection that have added to our understanding of new players in immune-related transplant rejection.

(613) - Influence of Non-Donor Specific Antibodies on Chronic Lung Allograft Dysfunction -A New Risk Factor in Lung Transplantation?

(613) - Influence of Non-Donor Specific Antibodies on Chronic Lung Allograft Dysfunction -A New Risk Factor in Lung Transplantation?

Evaluation of polyreactive monoclonal antibodies using HLA solid phase assays

It is well established that HLA antibodies play an important role in antibody-mediated rejection (AMR) and there is a growing body of literature demonstrating that non-HLA antibodies may also contribute to AMR. To study the source of non-donor specific HLA antibodies and self-reactive antibodies in patients with kidney graft loss, Porcheray et al. (Am J Transplant 2012; 12: 2088–2097) expanded immortalized polyreactive B-cell clones from a patient with kidney graft rejection and showed that some of these natural antibodies are cross-reactive to HLA and self-antigens. Gao et al. (Am J Transplant 2014; 14:1581–1591) also showed that the presence of IgG natural antibodies, with activity to apoptotic cells, correlates with late kidney allograft loss even after excluding patients with high reactivity to HLA. We have further characterized the HLA reactivity of 4 polyreactive B-cell clones isolated by Porcheray, Gao et al. using solid phase assays (Immucor, Inc.). We report here that while these clones do not react with HLA on the Immucor single antigen beads, they react to other HLA products, with some variation between different solid phase assays. Their reactivity appears to be enhanced upon denaturation, as judged by the monoclonal antibody 210.4, which reacts with denatured antigen, suggesting that they primarily react to cryptic epitopes. B. Ray: Employee; Company/Organization; Immucor.

(295) - The Time Course of Development of Anti-Human Leukocyte Antigen Antibodies Crucial for Monitoring and Potential Intervention Following Heart Transplantation

PurposeThe natural history of the production of circulating antibodies has not yet been clearly established. Recent technology has allowed for the improved detection of these antibodies. Antibody detection has been correlated to less optimal long term outcome. In our program we have been drawing blood for circulating antibodies at routine time periods including 1, 3, 6, 12 months and yearly after heart transplantation. Knowing when most antibodies develop will allow for appropriate monitoring and potential treatment.MethodsBetween 2010 and 2013, we assessed 193 heart transplant patients who at baseline had no circulating antibodies. Blood for antibodies was drawn at 1, 3, 6 and 12 months after heart transplant and yearly thereafter. Freedom from antibody production was assessed at each time period using Kaplan-Meier analysis.ResultsMost antibodies developed within 1 month after heart transplant in these antibody-naive patients (see circled - figure 1). This held true for both donor specific and non-donor specific antibodies (see circled - figure 2).ConclusionAntibody production appears to be most prevalent in the first month after heart transplant and should therefore designate these patients at risk for poor outcome after heart transplant. Strategies to prevent this antibody production should be pursued. PurposeThe natural history of the production of circulating antibodies has not yet been clearly established. Recent technology has allowed for the improved detection of these antibodies. Antibody detection has been correlated to less optimal long term outcome. In our program we have been drawing blood for circulating antibodies at routine time periods including 1, 3, 6, 12 months and yearly after heart transplantation. Knowing when most antibodies develop will allow for appropriate monitoring and potential treatment. The natural history of the production of circulating antibodies has not yet been clearly established. Recent technology has allowed for the improved detection of these antibodies. Antibody detection has been correlated to less optimal long term outcome. In our program we have been drawing blood for circulating antibodies at routine time periods including 1, 3, 6, 12 months and yearly after heart transplantation. Knowing when most antibodies develop will allow for appropriate monitoring and potential treatment. MethodsBetween 2010 and 2013, we assessed 193 heart transplant patients who at baseline had no circulating antibodies. Blood for antibodies was drawn at 1, 3, 6 and 12 months after heart transplant and yearly thereafter. Freedom from antibody production was assessed at each time period using Kaplan-Meier analysis. Between 2010 and 2013, we assessed 193 heart transplant patients who at baseline had no circulating antibodies. Blood for antibodies was drawn at 1, 3, 6 and 12 months after heart transplant and yearly thereafter. Freedom from antibody production was assessed at each time period using Kaplan-Meier analysis. ResultsMost antibodies developed within 1 month after heart transplant in these antibody-naive patients (see circled - figure 1). This held true for both donor specific and non-donor specific antibodies (see circled - figure 2). Most antibodies developed within 1 month after heart transplant in these antibody-naive patients (see circled - figure 1). This held true for both donor specific and non-donor specific antibodies (see circled - figure 2). ConclusionAntibody production appears to be most prevalent in the first month after heart transplant and should therefore designate these patients at risk for poor outcome after heart transplant. Strategies to prevent this antibody production should be pursued. Antibody production appears to be most prevalent in the first month after heart transplant and should therefore designate these patients at risk for poor outcome after heart transplant. Strategies to prevent this antibody production should be pursued.

Incidence and Impact of Anti-HLA-DP-Antibodies in Renal Transplantation.

Background: The role of HLA-DP-antibodies in renal transplantation is still poorly defined, whereas the clinical importance of DQ-antigens is widely accepted. This study aims to describe the incidence of donor- and non-donor specific antibodies against HLA-DP antigens in patients with renal transplantation. Methods: In a cohort of 112 kidney transplant patients, 97 recipients and their donors were typed for DP antigens by high-resolution sequence-specific oligonucleotides. Sera taken pre-transplant and at 1,3,6,9,12 months and annually post-transplant were retrospectively tested for anti-HLA-DP-antibodies using LABScreen single antigen bead. Results: In 43 (44.3%) patients, anti-HLA-DP-antibodies were found. 67.4% (n=29) were present in the pre-transplant sample and 32.6% (14) were exclusively found post-transplant. The median time from transplantation to antibody detection in the serum was 16.3 months. 71.4% (26) of the antibodies had a mean fluorescence intensity (MFI) between 1000 and 2000. 28.6% (17) had a MFI greater than 2000. There was no difference in MFI-levels between preformed and de novo anti-DP-antibodies. 50% (7) of the de novo anti-DP-antibodies accompanied de novo donor-specific antibodies (DSA) against HLA Class I (1), Class II (3) or both (3). 14% (2) were donor-specific antibodies. The 36 months graft survival was significantly reduced with de novo anti-DP-antibodies (p=0.012) (Figure 1): 50% (3) of the patients losing the graft within 36 months post-transplant had non-donor-specific anti-DP-antibodies. In two patients these antibodies accompanied donor-specific anti-DR- and DQ-antibodies.Figure: No Caption available.Conclusions: Antibodies against HLA-DP antigens are common in a cohort of renal transplantation and might have a harmful effect on the graft.

Role of Non-Donor Specific HLA Antibodies (NDSA) in Kidney Transplant Rejection.

Kidney transplant course is often complicated with development of Donor Specific Antibody (DSA) which have been associated with antibody-mediated rejection (ABMR) and poor allograft survival. However the role of Non-Donor Specific Antibody (NDSA) in occurrence of graft rejection and loss remains controversial. We studied patients who received a kidney transplant at Harper University Hospital from 2000-2010 and grouped them based on development of antibodies. The sera of patients were routinely screened for DSA and NDSA at 6 month to one year of transplant via ELISA or Luminex assay and only those with MFI >2500 were considered positive. The patients were evaluated for occurrence of biopsy proven acute rejection which was classified as cellular or ABMR per Banff criteria. Graft function was determined by most recent blood creatinine levels as of 12-31-2012 and graft loss was defined as need to return to dialysis or re-transplant and was censored for death. Of the 200 patients included in the study, 63 (31.5%) had NDSA only, 10 (5%) produced DSA only, 25 (12.5%) produced both and 102 (51%) non-producers at an average of 7.9 months post-transplant (range: 1-18 months). The baseline recipient characteristics were comparable except that recipients producing NDSA only or both were more likely to have had a previous transplant and therefore had higher peak PRA than non-producers and DSA only, which is suggestive of preformed NDSA due to prior sensitization. Those who produced both were more likely to be on maintenance steroid as compared to non-producing, NDSA only, and DSA only (12% vs. 32.35%, 22.22%, and 30% respectively; p<0.05). The fraction of patients with greater strength of DSA and NDSA i.e. MFI >10K was higher in the combined group than those in NDSA only (80% vs. 51.28%; p=NS) and DSA only (66.7% vs. 0%; p<0.05). There was an increased incidence of ABMR in those who produced both as compared to non-producers, NDSA only, and DSA only (20% vs. 3.92%, 1.59%, 0% respectively; p<0.01), while there was no difference in cellular rejection rates among the groups (p=NS). While the serum creatinine at last follow-up was not different between the groups, the graft loss was higher in those that produced both than others. In conclusion, NDSA alone especially at MFI <10K are not associated with increased risk of ABMR or graft loss. It is unclear if higher levels of NDSA are detrimental, especially in presence of DSA.

Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation

The long-term effect of rituximab and splenectomy on de novo HLA antibody production and chronic antibody-mediated rejection after renal transplantation is uncertain. In order to gain insight on this, we studied 92 ABO-incompatible and 228 ABO-identical/compatible consecutive renal transplant patients and determined their de novo HLA antibody production and graft outcome. Patients with pretransplant donor-specific antibodies had been excluded. ABO-incompatible transplants included 30 recipients treated with rituximab, 51 by splenectomy, or 11 with neither, due to low anti-A or -B antibody titer. Graft survival in ABO-identical/compatible patients (97.7% at 5 years) was significantly higher than in ABO-incompatible (87.0% at 5 years), rituximab (96.7% at 3 years), or splenectomy (85.7% at 5 years) patients. Only four patients had clinical chronic antibody-mediated rejection (two each identical/compatible and incompatible). There was no significant difference in prevalence of de novo HLA antibody, including donor-specific and nondonor-specific antibodies among ABO-identical/compatible patients (13.9%), patients receiving rituximab (14.3%) or splenectomy (13.2%), or among those receiving cyclosporine, tacrolimus, mycophenolate mofetil, mizoribine, and everolimus. Renal function remained stable in most recipients with de novo HLA antibody. Thus, neither pretransplant splenectomy nor rituximab treatment has an inhibitory effect on de novo HLA antibody production during medium-term follow-up. Further study on long-term effects is needed.

Behaviour of Non-Donor Specific Antibodies during Rapid Re-Synthesis of Donor Specific HLA Antibodies after Antibody Incompatible Renal Transplantation

BackgroundHLA directed antibodies play an important role in acute and chronic allograft rejection. During viral infection of a patient with HLA antibodies, the HLA antibody levels may rise even though there is no new immunization with antigen. However it is not known whether the converse occurs, and whether changes on non-donor specific antibodies are associated with any outcomes following HLA antibody incompatible renal transplantation.Methods55 patients, 31 women and 24 men, who underwent HLAi renal transplant in our center from September 2005 to September 2010 were included in the studies. We analysed the data using two different approaches, based on; i) DSA levels and ii) rejection episode post transplant. HLA antibody levels were measured during the early post transplant period and corresponding CMV, VZV and Anti-HBs IgG antibody levels and blood group IgG, IgM and IgA antibodies were quantified.ResultsDespite a significant DSA antibody rise no significant non-donor specific HLA antibody, viral or blood group antibody rise was found. In rejection episode analyses, multiple logistic regression modelling showed that change in the DSA was significantly associated with rejection (p = 0.002), even when adjusted for other antibody levels. No other antibody levels were predictive of rejection. Increase in DSA from pre treatment to a post transplant peak of 1000 was equivalent to an increased chance of rejection with an odds ratio of 1.47 (1.08, 2.00).ConclusionIn spite of increases or decreases in the DSA levels, there were no changes in the viral or the blood group antibodies in these patients. Thus the DSA rise is specific in contrast to the viral, blood group or third party antibodies post transplantation. Increases in the DSA post transplant in comparison to pre-treatment are strongly associated with occurrence of rejection.

Pediatric Heart Transplantation for Congenital and Restrictive Cardiomyopathy

Recent reports suggest worse outcomes in pediatric orthotopic heart transplantation (OHT) for congenital heart disease (CHD) and restrictive cardiomyopathy (RCM). We examined early outcomes in these diverse groups of patients in comparison with patients with dilatated cardiomyopathy (DCM). From 2000 to 2011, 209 patients were included: 50 with CHD, 23 with RCM, and 136 with DCM. Early survival was studied, as was the occurrence of acute rejection, donor-specific antibodies (DSAs) and nondonor-specific antibodies (NSDAs), incidence of pulmonary hypertension (PHT), right ventricular failure (RVF), and the need for mechanical circulatory support (MCS). The incidence of preoperative PHT was greatest in the RCM group (χ(2)p = 0.0006); the requirement for mechanical support before OHT was greatest in patients with DCM. Thirty-day survival was 92.0%, 97.1%, and 100% for patients with CHD, DCM, and RCM respectively. The incidence of RVF was highest for patients with RCM (43.5%; versus CHD, 26.0%; versus DCM, 14.7%). One-year survival estimates for patients with CHD, DCM, and RCM were 92.0%, 97.8%, and 82.6%, respectively (log-rank p = 0.165). Multivariable analysis revealed 4 significant risk factors for mortality: age, incidence of acute rejection, preoperative PHT, and the presence of NDSAs. The occurrence of DSAs was similar, although there was a significantly higher incidence of NDSAs in the CHD and RCM groups (36.0% and 30.4%, respectively, versus 14.0% in the DCM group; χ(2)p = 0.0024). Equivalent outcomes are achievable in pediatric OHT despite marked heterogeneity in anatomic and physiologic complexity in recipients. Physiologic factors such as PHT are likely to be more important than anatomic complexities in determining survival. The potential relevance of NDSAs warrants further investigation.

Chronic renal allograft damage after transplantation

Chronic renal allograft damage is one of the main problems after kidney transplantation. This review enumerates causes, describes available therapeutic options, and discusses options of the future. Alloantigen-dependent and alloantigen-independent factors are responsible for allograft damage. Prevention of renal allograft damage starts with interventions that occur surrounding the explantation in cadaveric organs. These include the use of dopamine or machine perfusion systems.Followed by the critical phase of ischemia/reperfusion injury, the LCN2/lipocalin-2, HAVCR1, and p38 MAPK pathway are new players involved in that process. Innate immunity plays a part, too. Cold ischemia time is associated with genes of apoptosis. Nondonor-specific antibodies like antihuman leukocyte antibodies-Ia or angiotensin type 1 receptor may also play a role. Recent research indicates that genetic polymorphism like the Ficolin-2 Ala258Ser polymorphism and the mannose-binding lectin-2 polymorphism are involved in that process. New therapeutic options are rare and in the future. However, there is some evidence that drugs interfering with metalloproteinases, sexual hormones like dihydroandrosterone, and mesenchymal stem cell therapy may be of importance. Taken together, although the understanding of chronic rejection has improved, the available therapeutic options remain scarce.

Monitoring of Circulating Antibodies in a Renal Transplantation Population: Preliminary Results

BackgroundThe presence of circulating antibodies (CA) against human leukocyte antigen (HLA) and major-histocompatibility-complexclass I–related chain A (MICA) antigens has been associated with worse renal function and reduced kidney allograft survival. We sought to describe the presence of donor-specific anti-HLA antibodies, non-donor specific antibodies, and antibodies against MICA antigens among a cohort of renal transplant recipients with respect to their evolution effects on renal function and occurrence of an acute rejection episode (AR) after transplantation. MethodsThis prospective study of 22 renal transplant recipients of deceased donor kidneys underwent studies of antibodies before and 3 months after grafting using Luminex technology. ResultsTen patients (five men and five women) showed preexistent CA. Comparing patients with versus without preformed CA, we did not observe a significant difference in donor and recipient age or gender. Eight patients (80%) with CA had undergone induction treatment with anti-human-activated T-lymphocyte rabbit immunoglobulin and 2 (20%) with basiliximab. There were no differences between groups regarding the incidence of acute rejection episodes (ARE n = 3 each). There was one case of Banff grade IIB ARE in a patient without preexisting CA; the other episodes were low-grade cellular responses. There were no differences in other variables including cold ischemia time, HLA mismatches, panel-reactive antibody levels, number of transfusions, cytomegalovirus infection or renal function at discharge and 3 months later. Retransplantation was the only factor associated with preformed CA. Retransplantation and preformed CA were associated with CA at 3 months after transplantation. ConclusionsCA monitoring is important for highly sensitized renal transplants, although our experience failed to show a difference in graft survival or renal function in the first 3 months' follow-up.

173-P

Aim Rarely are allografts reused following the death or critical unsuitability of the allograft in the original recipient. The “recycled” allograft carries not only the risk for sensitization against the donor HLA antigens, but also the possibility for HLA antibody production against the HLA antigens of the original recipient via passenger leukocytes. We describe here the case of a female recipient of an allograft kidney that had been previously transplanted and HLA antibodies against the donor and first recipient were detected. Methods HLA antibodies were assayed by LabScreen kits. Results The patient, an 48 year-old African American woman (HLA:A23,74; B7,14(Bw6,-); DR14,18; DQ4,6; DR52,-) was transplanted in 1996. The kidney donor was a 45 year-old male (HLA:A3,32; B7,44(Bw4,6); DR4,6; DQ3,-; DR53,-) originally transplanted in 1992 to a 58 year-old female (1st recipient HLA:A2,32; B44,57(Bw4,-); DR4,7; DQ3,-; DR53,-). Her post-transplant course was largely uneventful over 16 years with only three biopsy-proven rejection episodes (in 1996, 2004 and 2005) but without HLA antibody testing. Recent follow-up (>16 years post-transplant) showed evidence of both cellular and humoral rejection in conjunction with a possible history of non-adherence. At this time, HLA antibody monitoring was performed by Single Antigen testing, revealing reactivity to the donor B44 and DQ3 antigens. Interestingly, other HLA antibody specificities were also identified and showed reactivity to the first recipient (A2, B57, DR7). Other potential routes of HLA antigen sensitization were identified (including 3 blood transfusions in 2012 3 months before antibody testing), but no pregnancy information was available and could not be ruled out. Conclusions While we were unable to directly associate the non-donor specific HLA antibodies with the first recipient, antibody testing in this case suggests that passenger leukocytes might contribute to allo-sensitization when a donor allograft is used in multiple recipients.

Three-year outcome of isolated glomerulitis on 3-month protocol biopsies of donor HLA antibody negative patients

Transplant glomerulitis (TG) can lead to the diagnosis of acute humoral rejection when associated with C4d. Recent data have shown that, in patients with donor-specific antibodies, TG is a sign of humoral rejection, even in the absence of C4d. However, the clinical significance of isolated TG, i.e. TG without C4d deposition or morphological evidence of rejection, has not been specifically studied in protocol biopsies of recipients without donor-specific antibodies. We compared 20 isolated TG-patients with 44 selected recipients without TG or any rejection-associated change. The two groups had similar baseline characteristics. After a 3 year follow-up, renal function, acute rejection rate, and development of HLA antibodies were not significantly different between the two groups. Isolated TG had no deleterious consequences on the 3 year graft outcome. Eleven patients of the glomerulitis-group had another allograft biopsy during follow-up: glomerular lesions returned to normal in six patients whereas the persistence of glomerulitis or features consistent with chronic transplant glomerulopathy were noticed in the remaining five patients. Four of these five patients had pretransplant non-donor specific HLA antibodies. In conclusion, although isolated TG had no impact on allograft function at 3 year, histological outcome could be related to patient sensitization.

103 Pathologic Diagnosis of Antibody-Mediated Rejection of the Lung Allograft

The role of an antibody-mediated process in lung allograft rejection has not been elucidated. The purpose of this study is to evaluate the correlation of capillary inflammation and complement deposition in patients with anti-HLA Antibodies (DSAs), non-Donor Specific Antibodies (non-DSAs) and controls with no antibodies.