Complement-fixing Donor-specific Antibodies Research Articles

Missing Self-Induced Activation of NK Cells Combines with Non-Complement-Fixing Donor-Specific Antibodies to Accelerate Kidney Transplant Loss in Chronic Antibody-Mediated Rejection.

Binding of donor-specific antibodies (DSAs) to kidney allograft endothelial cells that does not activate the classic complement cascade can trigger the recruitment of innate immune effectors, including NK cells. Activated NK cells contribute to microvascular inflammation leading to chronic antibody-mediated rejection (AMR). Recipient NK cells can also trigger antibody-independent microvascular inflammation by sensing the absence of self HLA class I molecules ("missing self") on allograft endothelial cells. This translational study investigated whether the condition of missing self amplifies DSA-dependent NK cell activation to worsen chronic AMR. Among 1682 kidney transplant recipients who underwent an allograft biopsy at Lyon University Hospital between 2004 and 2017, 135 fulfilled the diagnostic criteria for AMR and were enrolled in the study. Patients with complement-fixing DSAs identified by a positive C3d binding assay (n=73, 54%) had a higher risk of transplant failure (P=0.002). Among the remaining patients with complement-independent chronic AMR (n=62, 46%), those in whom missing self was identified through donor and recipient genotyping exhibited worse allograft survival (P=0.02). In multivariable analysis, only proteinuria (HR: 7.24; P=0.01) and the presence of missing self (HR: 3.57; P=0.04) were independent predictors for transplant failure following diagnosis of chronic AMR. Cocultures of human NK cells and endothelial cells confirmed that addition of missing self to DSA-induced NK cell activation increased endothelial damage. The assessment of missing self at the time of diagnosis of chronic AMR identifies patients at higher risk for kidney transplant failure.

Increased Hazard of Chronic Lung Allograft Dysfunction in the Presence of Persistent and Complement Fixing Donor-Specific Antibodies

Purpose Long-term survival in lung transplant recipients (LTR) is limited in large part due to chronic lung allograft dysfunction (CLAD). Donor-specific antibodies (DSA) have been previously associated with more rapid high-grade rejection and mortality. Characteristics of these DSA may predict which antibodies are more harmful than others. The purpose of this investigation was to determine if C1q+ DSA is associated with increased CLAD in LTRs versus no DSA and C1q- DSA. Methods This was a single-center, retrospective cohort study of adult LTRs. Clinical data was extracted from the electronic medical record and laboratory systems. Patients were tested by Luminex Single Antigen Bead (SAB) IgG and C1q. IgG-SAB MFI > 1000 and C1q-SAB MFI > 500 were considered positive. DSA that were positive at more than one time point were classified as persistent, while those that were not were considered transient. Patients were grouped as no DSA, C1q- DSA, or C1q+ DSA. The primary outcome was CLAD. Secondary outcomes included CLAD subtypes of bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Outcomes were assessed using Kaplan-Meier methods and multivariable Cox regression with a time-dependent covariate. Results 582 LTRs were analyzed. 335 (57.6%) had no DSA, 194 (33.3%) were DSA+ C1q-, and 53 (9.1%) were DSA+ C1q+. Of 247 LTRs who developed any DSA, Class II DSA (206 LTRs, 84%) were more common than Class I DSA (106, 43%), including those with both classes. 177 LTRs (72%) had persistent DSA, including all 53 with C1q+ DSA . There was no difference in time to CLAD for any DSA vs no DSA (p=0.26). Patients with persistent DSA had shorter time to CLAD vs no DSA and transient DSA (p=0.04) and trended towards significance on multivariable assessment (HR: 1.70 95%CI: 1.00-2.92, p=0.05). DSA+ Cq1+ had shorter time to CLAD vs no DSA and DSA+ C1q- (p Conclusion Persistent DSA were associated with shorter time to CLAD. C1q+ DSA were associated with increased hazard of CLAD, BOS, and RAS. Larger cohorts are needed to evaluate other clinical outcomes.

Antibody-mediated rejection after liver transplantation-relevance of C1q and C3d-binding antibodies.

The aim of our study was to evaluate the relevance of complement-binding donor-specific antibodies (DSA) for prediction of antibody-mediated rejection (AMR) after liver transplantation. Sera from 123 liver transplant recipients were retrospectively defined for HLA specificity and complement-fixing activity using the single antigen beads, C1q and C3d techniques. Liver-recipients' sera were tested before transplantation, 3, 6 months and 1 year after transplantation. Patients were followed up for graft survival and rejection incidence for 1 year after transplantation. All patients with pretransplant complement-binding DSA developed severe AMR after transplantation, while three recipients out of four, who produced de novo complement-fixing DSA, developed AMR. Definition of DSA with respect to complement-fixing activity may provide clinically relevant information about the risk of AMR after liver transplantation.

OR51 To treat or not to treat: Long term stable kidney allograft function in presence of strong complement-fixing donor-specific antibody (DSA) to HLA-DQ alpha chain

The clinical significance of HLA antibody specific to the DQ alpha chain is controversial. Here we present a case of long term stable kidney allograft function in presence of strong de novo complement-fixing DQA DSA. A 27-year-old Caucasian male (non-sensitized; 0% CPRA) with ESRD to IgA nephropathy received a living donor kidney transplant (TX) 10+ years ago with a negative pre-TX CDC crossmatch (XM). Mismatched donor HLA were A1, A11, B8, DR13, DR17, DR52, DQ2, DQ6. Beginning 6 years post-TX, routine antibody screening by single antigen beads (SAB) revealed the emergence of de novo DQ antibody, with the reactivity to donor DQ2 and DQ6 initially detected at 700–10400 and 100–2400 MFI, respectively. Subsequent SAB profiles indicated that the DSA had progressively converted to be primarily directed against DQA1∗04/05/06, likely a result of sensitization from donor DQA1∗05:01. Epitope analysis suggested that the DSA was directed against a well-defined eplet 40GR3 shared by all DQA1∗04/05/06 alleles and may represent three distinct eplets 40G, 47C, 50V51L53Q, all located in the alpha-1 domain accessible to antibody binding. Testing by phenotype beads confirmed this strong DQA reactivity (5900–14100 MFI) and flow XM with surrogate donors expressing DQA1∗05 were strongly B-cell positive (210–420 MCS), suggesting the DSA was directed against native DQA chain. Functionally, C1q testing demonstrated the DQA DSA’s considerable ability to fix complement (5300–9500 MFI), while CDC XM with DQA1∗05 + surrogate donors were all negative. Despite the prolonged presence of this DQA DSA, other than an episode of acute cellular rejection (Banff II C4d-) diagnosed shortly after transplant which was promptly resolved, the patient’s 10 + years of post-TX course has been unremarkable with a stable kidney function (creatinine 1.5 ± 0.2 mg/dL; BUN 13.4 ± 2.7 mg/dL; GFR 55.0 ± 6.8 mL/min). This case highlights the fact that not all HLA DSA are created equal in terms of their clinical significance, and may also suggest a protective effect of a subset of DSA when directed against only to the DQ alpha chain. Download : Download high-res image (313KB) Download : Download full-size image

Antibody-mediated rejection in pediatric small bowel transplantation: Capillaritis is a major determinant of C4d positivity in intestinal transplant biopsies.

The diagnostic criteria for antibody-mediated rejection (ABMR) after small bowel transplantation (SBT) are not clearly defined, although the presence of donor-specific antibodies (DSAs) has been reported to be deleterious for graft survival. We aimed to determine the incidence and prognostic value of DSAs and C4d in pediatric SBT and to identify the histopathologic features associated with C4d positivity. We studied all intestinal biopsies (IBx) obtained in the first year posttransplantation (N=345) in a prospective cohort of 23 children. DSAs and their capacity to fix C1q were identified by using Luminex technology. Eighteen patients (78%) had DSAs, and 9 had the capacity to fix C1q. Seventy-eight IBx (22.6%) were C4d positive. The independent determinants of C4d positivity were capillaritis grades 2 and 3 (odds ratio [OR] 4.02, P=.047 and OR 5.17, P=.003, respectively), mucosal erosion/ulceration (OR 2.8, P=.019), lamina propria inflammation grades 1 and 2/3 (OR 1.95, P=.043 and OR 3.1, P=.016, respectively), and chorion edema (OR 2.16, P=.028). Complement-fixing DSAs and repeated C4d-positive IBx were associated with poor outcome (P=.021 and P=.001, respectively). Our results support that capillaritis should be considered as a feature of ABMR in SBT and identify C1q-fixing DSAs and repeated C4d positivity as potential markers of poor outcome.

(272) - Complement-Fixing Donor Specific Antibody and Pathologic Findings in Lung Allografts

(272) - Complement-Fixing Donor Specific Antibody and Pathologic Findings in Lung Allografts

Role of Pretransplant Complement-fixing Donor-specific Antibodies Identified by C1q Assay in Kidney Transplantation

BackgroundKidney transplant recipients who have pretransplant donor-specific human leukocyte antigen (HLA) antibodies have greater risk for developing allograft rejection and allograft loss. However, there is a varied effect of graft injury among patients with pretransplantation donor-specific antibodies (DSA). The difference of complement activating ability may be the reason why some DSA are detrimental to kidney allograft. This study aimed to investigate the association between pretransplantation C1q-binding DSA and clinical outcomes. MethodsThis retrospective study included 48 pretransplant sera from kidney transplant recipients who had pretransplant DSA with negative complement-dependent cytotoxic (CDC) crossmatches. The IgG DSA testing and C1q testing were performed on a Luminex platform with single antigen bead assay. The clinical outcomes between C1q-positive and C1q-negative groups were compared. ResultsC1q-positive DSA were detected in 12 out of 48 patients (25%). The incidences of antibody-mediated rejection (AMR) were higher among patients with C1q-positive DSA than patients with C1q-negative DSA (66.7% vs 41.7%). Nevertheless, there were no statistically significant associations between C1q-DSA and AMR (odds ratio 2.8, 95% CI 0.68–11.6, P = .13) and between C1q-DSA and graft loss (odds ratio 0.52, 95% CI 0.09–2.89, P = .44). The C1q-positive DSA group had significantly higher IgG DSA MFI than the C1q-negative DSA group (P < .001). ConclusionC1q-binding ability of DSA in pretransplant sera of kidney recipients was not associated with antibody-mediated rejection and graft loss post-transplantation. In contrast with the clinical relevance of C1q testing in the post-transplantation setting, C1q testing in pretransplant sera has limited use for immunological risk assessment.

Desensitization Strategies Pre- and Post-Cardiac Transplantation.

Panel reactive antibody (PRA) testing has become standard in the evaluation of patients prior to cardiac transplant. Sensitizing events such as blood transfusions, which result in the accumulation of pre-transplant antibodies, should be avoided as clinically feasible. Desensitization therapy might be considered in sensitized patients with cPRA > 50% although distinct cutoff PRA values for initiating therapy pre-transplant are patient and transplant program dependent. Post-cardiac transplant, quantitative antibodies should also be periodically analyzed, at intervals individualized to the patient. Donor-specific antibodies (DSA) after cardiac transplantation have been shown to be associated with worsened survival. It appears that complement fixing DSA confer the greatest risk for antibody-mediated rejection post-transplant. Desensitization strategies aim to reduce the number of clinically important antibodies prior to and after transplant, both by removal of antibodies and cessation of further production. Current desensitization regimens include pharmacologic, procedural, and surgical modalities, and must be individualized to the patient. Currently, most cardiac transplant programs tailor the post-transplant immunosuppressive regimen based on clinical factors and immunologic assays and may include the use of cytolytic induction and/or intravenous immune gammaglobulin in higher risk patients.

Correlation of Circulating Complement-Fixing Donor-Specific Antibodies Identified by the C1q Assay and Presence of C4d in Endomyocardial Biopsy Specimens.

Donor-specific antibodies (DSAs) are associated with increased cardiac graft loss. We applied a C1q solid-phase assay in parallel with the standard immunoglobulin G (IgG) single antigen bead (SAB) assay to examine the correlation of circulating complement-fixing donor-specific antibodies and the presence of C4d in endomyocardial biopsy (EMB) specimens. We retrospectively studied the relationship of C1q+ DSAs and C4d immunofluorescence (IF) in 49 EMB specimens from 44 heart transplant recipients who had concurrent EMB, C4d IF, and DSA measurements. We applied a C1q SAB in parallel with the standard IgG SAB assay to examine the DSA profiles in heart transplant patients posttransplant. A better concordance is observed between C1q+ DSAs with C4d IF+ compared with IgG DSAs with C4d IF + (40% vs 24%, P = .02). However, the correlation of C1q DSAs with C4d IF is not statistically significant (P = .24). Importantly, C1q+ DSAs were observed in 16 of 17 cases with C4d IF+; 24 cases had circulating C1q+ DSAs without detectable C4d staining, suggesting that that the presence of C1q+ DSAs may precede the detection of C4d deposition in EMB specimens and/or the development of antibody-mediated rejection. In this cohort of 44 patients, no significant correlation was observed between circulating C1q DSAs and C4d IF in EMB specimens. Additional studies are needed to further evaluate the association of C1q DSAs with EMB specimens and C4d staining.

Detection of alloantibody-mediated complement activation: A diagnostic advance in monitoring kidney transplant rejection?

ObjectiveAntibody-mediated rejection (ABMR) is an important cause of kidney allograft injury. In the last two decades, detection of complement split product C4d along transplant capillaries, a footprint of antibody-mediated classical complement activation, has evolved as a useful diagnostic marker of ABMR. While it was recognized that ABMR may occur also in the absence of C4d, numerous studies have shown that C4d deposition may indicate a more severe rejection phenotype associated with poor graft survival. Such studies suggest a possible diagnostic benefit of ex vivo monitoring the complement-activating capability of circulating alloantibodies. Design and methodsWe reviewed the literature between 1993 and 2015, focusing on in vivo (biopsy work-up) and in vitro detection (modified bead array technology) of HLA antibody-triggered classical complement activation in kidney transplantation. ResultsPrecise HLA antibody detection methods, in particular Luminex-based single antigen bead (SAB) assays, have provided a valuable basis for the design of techniques for in vitro detection of HLA antibody-triggered complement activation reflected by C1q, C4 or C3 split product deposition to the bead surface. Establishing such assays it was recognized that deposition of complement products to SAB, which critically depends on antibody binding strength, may be a cardinal trigger of the prozone effect, a troublesome in vitro artifact caused by a steric interference with IgG detection reagents. False-low IgG results, especially on SAB with extensive antibody binding, have to be considered when interpreting studies analyzing the diagnostic value of complement in relation to standard IgG detection. Levels of complement-fixing donor-specific antibodies (DSA) were shown to correlate with the results of standard crossmatch tests, suggesting potential application for crossmatch prediction. Moreover, while the utility of pre-transplant complement detection, at least in crossmatch-negative transplant recipients, is controversially discussed, a series of studies have shown that the appearance of post-transplant complement-fixing DSA may be associated with C4d deposition in transplant capillaries and a particular risk of graft failure. ConclusionsThe independent value of modified single antigen bead assays, as compared to a careful analysis of standard IgG detection, which may be affected considerably by complement dependent artifacts, needs to be clarified. Whether they have the potential to improve the predictive accuracy of our current diagnostic repertoire warrants further study.

(423) - Complement-Fixing Donor-Specific Antibody and Lung Transplant Outcomes

Complement-Fixing Donor-Specific Antibody and Lung Transplant Outcomes L. Chhatwani ,1 J. Mooney,1 R. Balestra,1 R. Lee,2 C. Lou,3 D. Weill,1 D. Tyan,3 G. Dhillon.1 1Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, CA; 2Department of Pharmacy, Stanford University Medical Center, Stanford, CA; 3Department of Pathology, Stanford University Medical Center, Stanford, CA.

2-P

Aim The method of choice in most of the HLA laboratories for the identification of anti HLA antibodies is the solid phase assay Luminex technology. This method is very sensitive and it is being used for virtual crossmatching as well as for paired kidney exchange (PKE) programs. The most challenging factor for the paired kidney exchange programs is the high sensitization level of the listed couples determined by Luminex-IgG MFI. Now it is increasingly believed that the complement fixing donor specific antibodies (DSA) are the more clinically relevant than non-complement fixing antibodies. In this study we determined impact of using Luminex C1q instead of Luminex-IgG in the pool of the couples listed in our PKE program. Methods A cohort of 12 patients was chosen randomly from the total of 28 couples constituting our HLA incompatible PKE program. All samples were tested by Luminex-IgG and Luminex-C1q (One Lambda) for HLA class I and II antibodies. The unacceptable antigens listed in the PKE are those with more than 6000 MFI for HLA-A,B,DR and DQ. For HLA-C it was 10000 MFI. Results The percentage of complement fixing antibodies detected for HLA class I and II were 36% and 35% respectively. When the unacceptable antigens entered in the PKE program were those Luminex-IgG positive, there were no exchangeable pairs. However when the unacceptable antigens entered in the PKE program were only those C1q positive, we found four one-way exchangeable pairs. Conclusions Our data suggest that we should consider listing unacceptable antigens in the PKE program using the Luminex-C1q positive instead of Luminex-IgG positive. Listing unacceptable antigen in the PKE program solely based on Luminex-IgG will deprive many patients from being transplanted with compatible pairs.

4-P

In combined liver kidney (CLK) transplants (Txp), the kidney is not always protected from rejection when pre-Txp donor specific antibodies (DSA) are present. We applied a C1q solid-phase assay to examine complement-fixing DSA in CLK Txps who developed accelerated antibody mediated rejection (AMR). Four CLK Txps who had high PRA and high levels of DSA pre-Txp were evaluated. Pre- and post-Txp sera were analyzed for DSAs using commercially available single-antigen bead assay kits. The MFI cut off values of IgG DSA and C1q+ DSA are >1,000 and >300 respectively. Two of these 4 recipients (case 1 and 2) experienced biopsy-proven AMR during the first 2 weeks post-txp. All 4 cases had a persistent Post-Txp IgG DSA (Table). The 2 subjects who developed AMR had very high pre-Txp C1q+ DSA levels (MFI range for single specificity: 10,800-17,500). In contrast, case #3 who had relatively lower pre-Txp C1q DSA (MFI= 4,400) did not experience AMR.[ Table 1 ] With the limitation of small number of cases, the presence of high levels of pre-Txp C1q+ DSA appears to be associated with an increased risk of AMR of the kidney. Future studies should evaluate the risk of AMR and long-term outcomes associated with the presence of C1q+ DSA during the pre- and post-Txp periods in CLK Txps.

58-P: CORRELATION OF CIRCULATING COMPLEMENT-FIXING DONOR SPECIFIC ANTIBODIES IDENTIFIED BT THE C1q ASSAY AND PRESENCE OF C4d in ENDOMYOCARDIAL BIOPSY: A SINGLE-CENTER RETROSPECTIVE STUDY

Aim Donor-specific antibodies (DSA) are associated with increased cardiac graft loss. Detection of antibody-mediated rejection (AMR) relies on graft dysfunction, C4d immunofluorescence (IF) and DSA. We applied a C1q solid-phase assay in parallel with the standard IgG SAB assay to examine the correlation of circulating complement-fixing donor-specific antibodies and presence of C4d in endomyocardial biopsy (EMB). Methods We retrospectively studied the relationship of C1q+ DSA, and C4d IF in 40 EMB from 38 cases of heart transplant recipients (The Journal of Heart and Lung Transplantation, Vol 32, No 4, April 2013). C4d evaluation was performed for cause, including (1) clinical evidence of graft dysfunction; (2) high PRA; and (3) ACR, ISHLT Grade 3R. We applied a C1q solid-phase assay in parallel with the standard IgG SAB assay to examine the DSA profiles in heart transplant patients post-transplant. The MFI cut off values of IgG DSA and C1q+ DSA are > 1,000 and >200 respectively. Results A better concordance is observed between C1q+ DSA with C4d IF+ as compared to IgG DSA with C4d IF+ (54% vs.24%, p = 0.09, paired samples T test). However, the correlation of C1q DSA with C4d IF is not statistically significant ( p = 0.12, Fisher Exact test). Importantly, C1q+ DSA is observed in 14/15 cases with C4d IF +; 17 cases had circulating C1q+ DSA without detectable C4d staining (Table), suggesting that that the presence of C1q+ DSA may precede the detection of C4d deposition in EMB and/or the development of AMR. [ Table 1 ] Conclusions In this cohort of 38 patients, no significant correlation is observed between circulating C1q DSA and C4d IF in EMB. Additional studies are needed to further evaluate the association of C1q DSA with EMB and IF C4d staining, and with long-term outcomes in heart transplant recipients.

Solid phase detection of C4d-fixing HLA antibodies to predict rejection in high immunological risk kidney transplant recipients

Protocols for recipient desensitization may allow for successful kidney transplantation across major immunological barriers. Desensitized recipients, however, still face a considerable risk of antibody-mediated rejection (AMR), which underscores the need for risk stratification tools to individually tailor treatment. Here, we investigated whether solid phase detection of complement-fixing donor-specific antibodies (DSA) has the potential to improve AMR prediction in high-risk transplants. The study included 68 sensitized recipients of deceased donor kidney allografts who underwent peritransplant immunoadsorption for alloantibody depletion (median cytotoxic panel reactivity: 73%; crossmatch conversion: n=21). Pre and post-transplant sera were subjected to detection of DSA-triggered C4d deposition ([C4d]DSA) applying single-antigen bead (SAB) technology. While standard crossmatch and [IgG]SAB testing failed to predict outcomes in our desensitized patients, detection of preformed [C4d]DSA (n=44) was tightly associated with C4d-positive AMR [36% vs. 8%, P=0.01; binary logistic regression: odds ratio: 10.1 (95% confidence interval: 1.6-64.2), P=0.01]. Moreover, long-term death-censored graft survival tended to be worse among [C4d]DSA-positive recipients (P=0.07). There were no associations with C4d-negative AMR or cellular rejection. [C4d]DSA detected 6months post-transplantation were not related to clinical outcomes. Our data suggest that pretransplant SAB-based detection of complement-fixing DSA may be a valuable tool for risk stratification.

69-P

Aim It is widely believed that complement fixing donor specific antibody is more clinically relevant than non-complement fixing antibody. However, the C1q assay, which is used to determine if there is complement fixing Donor Specific Antibody (DSA) is time consuming and expensive. We wanted to study if the Luminex Single Antigen (SA) MFI level is related to the presence of C1q fixing antibody. Methods Twelve kidney recipient sera, demonstrating a total of 29 anti-HLA DSAs by the SA assay (One Lambda, Canoga Park, CA) were tested by the C1q assay (One Lambda, Canoga Park, CA). Results Five of these sera demonstrated C1q fixing DSAs. The average MFI of the SA for these positive sera was 17,920. The average MFI of the SA for the sera not having C1q antibody specificities was 4776. There were three sera that had relatively high MFI values that were not positive by the C1q assay (MFI average 12,269) [Fig. 1]. Download full-size image Conclusions The strength of the MFI in classical Luminex SA testing has a high predictive value for positivity in the C1q assay. We found that sera with greater than 13,000 MFI by Luminex SA had a high probability of being positive by the C1q assay. Therefore, the use of the classical Luminex SA assay to determine the strength of the MFI is beneficial to determine if reflex C1q testing is warranted.

172-P

Aim To present and discuss the presence of post transplant (tx) donor specific antibody (DSA) and compare methods for detection of this antibody (Ab). Methods Donor and recipient class I (A,B,C) and II (DR,DQ) were typed by SSP. Ab screening was performed using FlowPRA ® Screening beads and Ab identification was performed using LabScreen ® Single Antigen Beads. The C1qScreen™ assay was used to assess for complement fixing antibodies. Typing and Ab reagents were from One Lambda Inc. T and B cell CDC NIH extended crossmatch (XM) was performed pre-tx. Post tx T and B cell flow crossmatch (FCXM) was performed using standard local protocol including pronase treatment. Results The patient received a deceased donor kidney tx in 1994; there were 5 mismatched antigens (A2,B35,Cw4,DR1, and DQ5). Pre-tx CDC XM was T and B cell negative (neg). Recipient was screened for HLA Ab in 2005. Renal function was stable. FlowPRA results were 0% (I) and 76% (II). DSA to DQ5 was detected. Due to stable function, patient was monitored with no treatment. DSA remained present and creatinine levels began to increase in 2008. The B cell FCXM result was positive with sera from 2008 and 2010. The patient was treated with rituximab and high dose IVIg in January, 2011. The B cell FCXM became neg although creatinine remained high initially. Creatinine levels began to drop and returned to baseline by January 2012. The B cell FCXM result remained neg but high MFI DQ5 DSA were still detected. Results from the C1q assay showed complement fixing DSA in the 2008 serum but there were no C1q reactive Ab in the serum from 1 year post treatment thus no complement fixing DSA. Conclusions DSA was detectable 3 years before clinical evidence of graft dysfunction. The C1q assay results appear to correlate better with the FCXM results. The predictive value of a high MFI DSA does not appear to be consistent with the FCXM result. In this case, the FCXM result appears to be a better assessment of the impact of therapy than the MFI value of DSA (DQ5).

Complement fixing donor-specific antibodies and allograft loss

Complement fixing donor-specific antibodies and allograft loss

108-P C4d+ antibody mediated rejection in absence of complement fixing donor specific antibody for a heart transplant patient

108-P C4d+ antibody mediated rejection in absence of complement fixing donor specific antibody for a heart transplant patient