ABO Titers Research Articles

Practice of ABO antibody titration in a transplant center: From tube method to manual gel column testing to automated column agglutination technology.

High-quality ABO antibody titre testing is required for ABO-incompatible haematopoietic stem cell transplantation and kidney transplantation. To assess the feasibility of automated ABO titration as an alternative to manual and semi-automatic titration during the peri-transplant period, a comparative study was conducted internally in a transfusion medicine laboratory. This study was performed in two stages. Firstly, the differences in anti-A/B detecting using conventional tube test (CTT) and manual column agglutination technology (CAT) were compared in group O pregnant women. Then, manual and automated CAT were applied to simultaneously detect ABO antibody levels in non-AB-group adult haematological oncology patients. In the first stage, four groups of 192 comparable results were generated from 48 subjects, which showed a high correlation between CTT and manual CAT (p < 0.001). However, the detection sensitivity of the latter was at least 1 fold higher dilution than that of the former. Fifty-six patients were tested in the second stage by simultaneous manual and automated CAT, and the paired titers differed within an acceptable range (±1 fold dilution). However, the concordance was slightly higher in group IgM (85.4%) than in group IgG (80.5%). Blood group specificity of ABO titers was also observed in this population, and no association between titers and other factors was found. Automated CAT standardises ABO titre testing and saves labor costs, although manual review of weak positive reactions is still necessary. Due to the blood group specificity of ABO antibodies, special attention should be paid to the quality control and clinical relevance of titre testing for group O recipients in ABO-mismatched transplantation.

ABO isoagglutinin titers in group "O" blood donors.

High titers of anti-A and anti-B are considered to be one reason for hemolytic transfusion reactions and ABO hemolytic disease in fetus and neonates. There is no consensus for critical ABO antibody titers to guide transfusion or transplant decisions. Implementation of ABO titer measurement can favor reduction in transfusion reactions in nongroup "O" recipients. This study aimed to understand the trend and quantification of anti-A and anti-B antibody titers in Group "O" donors in this geography. A prospective study was conducted in 218, Group "O" blood donors in the year 2021, during the COVID-19 pandemic. Immunoglobulin (Ig) M antibody titers were measured by hemagglutination and IgG titers by solid-phase red cell adherence. Antibody titers ≥128 for IgG and ≥64 for IgM were considered "high titers." Epi Info 7.1 software was used for statistical analysis, with P < 0.05 significant. About 96.75% of blood donors were male with a median age of 33.16 ± 8.8 years. ABO antibody titers ranged from 0 to 1024. The prevalence of titers of <128 for IgG anti-A and anti-B was 79.36% and 86.24%, respectively, and 88.53% for both anti-A and anti-B IgM (<64). High IgG anti-A antibody titers were exhibited in 20.64% and anti-B titers in 13.76% of donors. None of the recipients showed any hemolytic reactions. The donor population showed predominance of low isoagglutinin titers. Defining critical titers will help formulate institutional guidelines on ABO-incompatible platelet transfusions and transplants. The use of automation in ABO titer assays removes interobserver variations and offers precise, reproducible, and less labor-intensive assays in resource-constrained settings.

A prospective observational study to evaluate effect of heat inactivation on ABO titers performed by column agglutination technology and conventional tube technique.

When determining ABO antibody titers, immunoglobulin G (IgG) antibodies can be masked by immunoglobulin M (IgM) antibodies. Hence, the measurement of actual concentration of IgG requires methods like heat inactivation (HI) of plasma. This study was aimed at determining the effects of HI on IgM and IgG titers performed by conventional tube technique (CTT) and column agglutination technique (CAT). This was a prospective, observational study conducted from October 2019 to March 2020. All consecutive A, B, and O group donors who gave consent for participation were included. All samples were consecutively tested by CTT and CAT, before and after HI (pCTT, pCAT). A total of 300 donors were included. IgG titers were found to be more than IgM titers. For group O, IgG titer results were higher for both anti-A and anti-B compared to group A and B. For group A, B, and O, pretreatment results were higher than posttreatment IgG titer results. Median anti-A titers were similar to median anti-B titers across all categories. Median IgM and IgG titers were higher for group O individuals than nongroup O individuals. There was reduction in IgG and IgM titers after HI of plasma. One log reduction in median titers was observed when ABO titers were performed by CAT and CTT. There is one log difference between median antibody titers estimated using heat inactivated and nonheat inactivated plasma. The use of HI for ABO isoagglutinin titer estimation can be considered in low resource settings.

Can Donor Demography or Anthropometry be Used as a Screening Tool for Identifying Potential Low ABO-Titer Plasma?

Background and Aims: Titration is a time-consuming procedure even when automated. The aim of the present study was to identify the variation in ABO titers with donor characteristics in Group O individuals. Materials and Methods: This was a prospective, observational study conducted from January 2019 to March 2020. All consecutive O group donors were included. All samples were tested by conventional tube technique (CTT). Demographic and anthropometric details of the donors such as gender, age, religion, height, weight, first-time/repeat donor, and state of residence were recorded. The high-titer group included individuals with anti-A and anti-B ≥128, and the low-titer group included individuals with anti-A and anti-B &lt;128. Results: A total of 2000 Group O whole blood donors were included. A higher percentage of donors were older than 30 years of age (55.3%), males (90.7%), Hindu (87.15%), belonging to Uttar Pradesh (70.85%), height more than 160 cm (88.85%), weight more than 65 kg (82.2%), body mass index (BMI) more than 23 (86.15%), body surface area more than 1.7 m2 (89.95%), and first-time donors (68.4%). The donor age, height, weight, BMI, and body surface area were found to have a weak correlation with anti-A and anti-B titers performed by CTT. The correlation between female and male gender was poor in high- as well as low-titer category. Conclusion: A definite variation in antibody titers is seen with a change in donor demographics and anthropometrics. However, none of the variables helps as a screening tool for identifying the North Indian healthy donors who possess a high or low titer.

A Prospective Observational Study to Compare Heat Inactivated ABO Isoagglutinin Titres Performed by CTT and CAT with Solid Phase Red Cell Adhesion (SPRCA) in O Blood Group Individuals

Measurement of actual concentration of IgG requires methods like heat inactivation (HI) of plasma. This study was aimed at comparing of heat treated ABO titers performed by conventional test tube technique (CTT) and column agglutination technique (CAT) with HA/SPRCA.

Comparative Evaluation of Heat-Inactivated ABO Isoagglutinin Titers with Solid-Phase Red Cell Adhesion Titers

Background and Objectives: Measurement of actual concentration of IgG requires methods like heat inactivation (HI) of serum. This study was aimed at comparing of heat-treated ABO titers performed by conventional test tube technique (CTT) and column agglutination technique (CAT) with hemagglutination (HA)/solid-phase red cell adherence (SPRCA). Methods: This was a prospective, observational study conducted between October 2019 and March 2020. All consecutive A, B, and O group donors who gave consent for participation in the project were included. All samples were tested by CTT and CAT before and after HI (post DTT treatment performed by CTT [pCTT] and post DTT treatment performed by CAT [pCAT]) and with HA/SPRCA. Results: A total of 300 donors were included: 100 each with A, B, and O blood groups. For group O, IgG titers were higher than IgM titers among group O, whereas that among group A and group B, IgM titer was found to be higher than IgG titer by both HA/SPRCA and pCTT. The titer values among all the three blood groups were highest when the test was performed by pCAT, though the results of pCTT and SPRCA, pCTT, and pCAT were significant in group O donors. For groups A and B, results of pCTT and pCAT, pCAT, and HA/SPRCA were found to be statistically significant. Conclusion: Results obtained by HA/SPRCA were closer to pCTT, with respect to time consumption, expertise required, and lack of inter-observer variation. Titers obtained by pCAT were higher in comparison to pCTT obviously due to its relative higher sensitivity. Hence, these methods cannot be used interchangeably.

Comparative evaluation of DTT treated ABO isoagglutinin titres performed by two methods with solid phase red cell adhesion (SPRCA) titres.

Measurement of actual concentration of IgG requires methods like treatment of serum with dithiothreitol (DTT). This study was aimed at comparing of DTT treated ABO titres performed by conventional test tube technique (CTT) and column agglutination technique (CAT) with HA/SPRCA. This was a prospective, observational study conducted from October 2019 to March 2020. All consecutive A, B and O group donors who gave consent for participation were included. All samples were tested by CTT and CAT before and after DTT treatment (pCTT, pCAT) and with HA/SPRCA. A total of 300 donors were included; 100 each from A, B and O blood group donors. Group O titres were higher than group A/B titres. Group O titres were highest when performed by pCAT, followed by pCTT and lowest by HA/SPRCA. Group A/B titres were highest when performed by HA/SPRCA, followed by pCAT and pCTT for anti-A and highest when performed by pCAT, followed by HA/SPRCA and lowest by pCTT for anti-B. Results obtained by pCAT were closer to results obtained by pCTT, whereas those obtained by HA/SPRCA were variable. SPRCA offers the advantage of automation, no inter-observer variation and less time consumption because IgM interference is not observed with SPRCA, thus providing an alternative to pCTT. However, these methods cannot be used interchangeably and to discern the most suitable method, a clinical impact of these results needs to be studied.

Kidney Transplantation with ABO-Incompatible Donors: A Comparison with Matched ABO Compatible Donor Transplants.

Introduction:ABO-incompatible kidney transplantation (ABOiKTx) expands the living donor pool. There is limited long-term outcome data from India especially in comparison with ABO-compatible kidney transplantation (ABOcKTx). Here we report outcomes of the first 100 ABOiKTx compared to ABOcKTx from our center.Methods:Between August 2013 and December 2019, 100 consecutive ABOiKTx were compared with 100 ABOcKTx done during the same period.Controls were matched for age, donor characteristics, HLA mismatches, and date of transplantation.Results:Mean (SD) follow up period was 25.9 ± 20.5 and 27.2 ± 20.6 months in ABOi and ABOcKTx respectively. Patient survival at 1 and 5 years post-transplant was 93.3 and 73.5% vs. 95.4 and 93% (P = 0.03), while graft survival rates were 85 and 60% vs. 93.1 and 83% in ABOi and ABOcKTx respectively (P = 0.03). The incidence of antibody-mediated rejections was 15% vs. 4%, and that of T-cell-mediated rejections was 10 vs. 12% respectively. Infections, malignancies, and surgical complications were similar. Level of anti ABO titers, HLA mismatches, recipient age, donor age, and presence of diabetes did not impact graft survival amongst ABOiKTx. The predicted survival and incidence of acute rejections and infections in the later 50 ABOiKTx transplants were better than the first 50 ABOiKTx when compared to their respective controls.Conclusion:Outcomes of ABOiKTx were inferior to ABOcKTx but tends to improve as more experience is gained. Incidence of ABMR was higher but infections and surgical complications were comparable. This data provides evidence that ABOiKTx is viable option for those without a ABO compatible donor.

Changing patterns of clinical decision making: are falling numbers of antibody incompatible transplants related to the increasing success of the UK Living Kidney Sharing Scheme? A national cohort study

Antibody incompatibility is a barrier to living kidney transplantation; antibody incompatible transplantation (AIT) is an accepted treatment modality, albeit higher risk. This study aims to determine changes to clinical decision making and access to AIT in the UK. An electronic survey was sent to all UK renal transplant centres (n=24), in 2014, and again in 2018. Questions focused on entry & duration in the UKLKSS for HLA and ABO-incompatible pairs, Can and provision of direct AIT transplantation within those centres. Between 2014 & 2018, the duration recommended for patients in the UKLKSS increased. In 2014, 34.8% of centres reported leaving HLA-i pairs in the UKLKSS indefinitely, or reviewing on a case by case basis, by 2018 this increased to 61%. Centres offering direct HLA-i transplantation reduced from 58% to 37%. For low titre (1:8) ABO-i recipients, 66% of centres recommended at least 9months (3 matching runs) in the UKLKSS scheme in 2018, compared to 47% in 2014, 50% fewer units consider direct ABO-i transplantation for unsuccessful pairs with high ABO titres (>1:512). Over time, clinicians appear to be facilitating more conservative management of AIT patients, potentially limiting access to living donor transplantation.

Individualized Preconditioning for ABO-Incompatible Living-Donor Kidney Transplantation: An Initial Report of 48 Cases from China.

BackgroundABO-incompatible (ABOi) living-donor kidney transplantation (KTx) is well established in developed countries, but not yet in China.Material/MethodsWe developed individualized preconditioning protocols for ABOi KTx based on initial ABO antibody titers. After propensity score matching of ABOi with ABO-compatible (ABOc) KTx, post-transplant outcomes were compared.ResultsBetween September 2014 and June 2018, 48 ABOi living-donor KTx candidates received individualized preconditioning, and all underwent subsequent KTx (median initial ABO titers: 16 for IgM and 16 for IgG). Thirty-one recipients (64.6%) were preconditioned with rituximab (median dose: 200 mg, range: 100–500 mg). Among 37 patients (77.1%) who received pre-transplant antibody removal, the median number of sessions of antibody removal required to achieve ABOi KTx was 2 (range: 1–5), which was conducted between days −10 and −1. Eleven ABOi recipients (22.9%) were preconditioned with oral immunosuppressants alone. Hyperacute rejection led to the loss of 2 grafts in the ABOi group. After a median follow-up of 27.6 months (ABOi group) and 29.8 months (ABOc group), there were no significant differences in graft/recipient survival, rejection, and infection. There were marginally higher rates of severe thrombocytopenia (<50×109/L) (P=0.073) and delayed wound healing (P=0.096) in ABOi recipients.ConclusionsOur individualized preconditioning protocol evolved as our experience grew, and the short-term clinical outcomes of ABOi KTx did not differ from those of matched ABOc patients. ABOi KTx may be a major step forward in expanding the kidney living-donor pool in China.

Distribution of Anti-ABO Immunoglobulin G Subclass and C1q Antibody in ABO Incompatible Kidney Transplantation

Introduction To investigate the correlation between serum anti-ABO immunoglobulin G (IgG) and IgG subtypes, anti-ABO IgG subclasses were measured by flow cytometry (FCM) in ABO-incompatible (ABO-i) kidney transplant recipients (KTRs). We also evaluated baseline anti-ABO C1q antibody of KTRs. Method Baseline anti-ABO IgG titers were measured with both FCM and column agglutination technique (CAT) methods in 18 ABO-i KTRs. The mean florescence intensity (MFI) ratios of baseline Anti-ABO IgG subclasses were obtained by FCM method and followed up after rituximab (RTX), each plasmapheresis (PP) session and kidney transplantation. Correlation between the values of IgG subclass and total IgG titer were analyzed. Baseline anti-ABO C1q antibody was measured by FCM methods. Result The baseline MFI ratios of total IgG, IgG1, IgG2, IgG3 and IgG4 were 202.46, 62.41, 30.01, 1.04 and 1.13, respectively. The MFI ratios of IgG1, IgG2, and total IgG measured at baseline and pre-PP were positively correlated with the baseline ABO titer measured by CAT (rho, baseline; 0.641, 0.638, 0.663, PP; 0.662, 0.581, 0.662). However, Spearman correlation analysis revealed that baseline ABO titer did not show any correlation with the values after final PP and transplantation. IgG1 and IgG2 as well as total IgG were removed effectively after serial PP. However, anti-ABO C1q antibody was not detected and neither correlated with total IgG and any IgG subclasses. Conclusion Our findings suggest that IgG1 and IgG2 are dominant IgG subtypes in ABO-i KTRs. The mean baseline levels of IgG1 and IgG2 were correlated with baseline total IgG titer. However, anti-ABO C1q antibody was not detected in the present study. Further study is warranted to evaluate the function of each IgG subtype to activate complement pathway.

Distribution of Anti-ABO Immunoglobulin G Subclass and C1q Antibody in ABO-incompatible Kidney Transplantation

IntroductionTo investigate the correlation between serum anti-ABO immunoglobulin G (IgG) and IgG subclasses, anti-ABO IgG subclasses were measured by flow cytometry (FCM) in ABO-incompatible (ABOi) kidney transplant recipients. We also evaluated baseline anti-ABO C1q antibody. MethodBaseline anti-ABO IgG titers were measured by both FCM and column agglutination technique methods in 18 ABOi kidney transplant recipients. The mean florescence intensity (MFI) ratios of baseline anti-ABO IgG subclasses and anti-ABO C1q antibody were obtained by FCM and followed-up after rituximab treatment, each plasmapheresis (PP) session, and kidney transplantation. Correlation between the values of IgG subclass and total IgG titer was analyzed. ResultsThe baseline MFI ratios of total IgG, IgG1, IgG2, IgG3, and IgG4 were 202.46, 62.41, 30.01, 1.04, and 1.13, respectively. The MFI ratios of IgG1, IgG2, and total IgG measured at baseline and pre-PP were positively correlated with the baseline ABO titer was measured using the column agglutination technique. The numbers of PP sessions to reach the target titer were correlated with the baseline IgG and IgG1 levels. IgG1 and IgG2 as well as total IgG were removed effectively after serial PP. Anti-ABO C1q antibody was neither detected nor correlated with total IgG and any IgG subclasses. ConclusionsOur findings suggest that IgG1 and IgG2 are the dominant IgG subclass in ABOi kidney transplant recipients. Baseline levels of IgG1 and IgG2 were correlated with baseline total IgG titer. However, anti-ABO C1q antibody was not detected in the present study.

Comparison of antibody titers using conventional tube technique versus column agglutination technique in ABO blood group incompatible renal transplant.

INTRODUCTION:Measurement of alloantibody titer to a red cell antigen (ABO titers) is an integral part of management of ABO incompatible kidney transplants (ABOiKT).MATERIAL AND METHODS:There are different methods of titer estimation. Alloantibody detection by tube titration and Gel agglutination columns are accepted methodologies. It is essential to find the difference in titers between the two methods so as to set the 'cut-off' titer accordingly, depending upon the method used.RESULTS:We did a prospective observational study to compare and correlate the ABO titers using these two different techniques – conventional tube technique (CTT) and the newer column agglutination technique (CAT). A total of 67 samples were processed in parallel for anti-A/B antibodies by both tube dilution and column agglutination methods. The mean titer by conventional tube method was 38.5 + 96.6 and by the column agglutination test was 96.4 + 225. The samples correlated well with Spearman rho correlation coefficient of 0.94 (P = 0.01).CONCLUSION:The column agglutination method for anti A/B titer estimation in an ABO incompatible kidney transplant is more sensitive, with the column agglutination results being approximately two and half fold higher (one more dilution) than that of tube method.

Borderline rejection in ABO-incompatible kidney transplantation.

The clinical results of ABO-incompatible (ABOi) and ABO-compatible (ABOc) kidney transplantation (KT) are similar. Protocol kidney biopsies (PKB) of ABOi transplant recipients show positivity for C4d without evidence of antibody-mediated rejection (ABMR), but little is known about the histologic progression. We evaluated histologic parameters in PKB at 12months and also compared clinical outcome at 1year. This is a prospective observational study conducted between 2009 and 2013. We performed 146/30 ABOc/ABOi consecutive living-donor KT with PKB as well as additional indication biopsies. In the ABOi group, the desensitization protocol consisted of rituximab, plasma exchange or immunoadsorption, and immunoglobulins. In indication biopsies during the first year, T-cell-mediated rejection Banff ≥immunoadsorption was 8.2% vs 6.7% (P=.561) and ABMR 4.8% vs 13.3% (P=.095). At 1year, PKB (ABOc/ABOi) showed differences in borderline rejection lesions (6.8% vs 23.3% [P=.012]) and in C4d positivity in the ABOi group (P=.001). Interstitial fibrosis and tubular atrophy (IFTA) lesions (ABOc/ABOi) were 68.4% vs 63.2% (P=.348). Transplant glomerulopathy was 0.7% vs 3.3% (P=.373) at 1year. Our PKB ABOi series shows at 1year more borderline lesions independent of ABO titers, HLA incompatibility, and the presence of antidonor antibody, but do not show more IFTA nor transplant glomerulopathy. No clinical differences were observed between ABOi and ABO transplants.

Role of Therapeutic Plasma Exchange in Reducing ABO Titers in Patients Undergoing ABO-Incompatible Renal Transplant

Abstract Background/aims Our study presents an analysis of the trends of ABO antibody titers and the TPE (therapeutic plasma exchange) procedures required pre- and post-ABO-incompatible renal transplant. Methods Twenty-nine patients underwent ABO-incompatible renal transplant during the study period. The ABO antibody titers were done using the tube technique and titer reported was the dilution at which 1+ reaction was observed. The baseline titers of anti-A and anti-B antibodies were determined. The titer targeted was ≤8. Patients were subjected to 1 plasma volume exchange with 5% albumin and 2 units of AB group FFP (fresh frozen plasma) in each sitting. TPE procedures posttransplant were decided on the basis of rising antibody titer with/without graft dysfunction. Results The average number of TPE procedures required were 4–5procedures/patient in the pretransplant and 2–3procedures/patient in the posttransplant period. An average titer reduction of 1serial dilution/procedure was noted for anti-A and 1.1serial dilution/procedure for anti-B. Number of procedures required to reach the target titer was not significantly different for anti-A and anti-B ( p =0.9). The number of TPE procedures required pretransplant does not differ significantly with the baseline titers ( p =0.062). Outcome of the transplant did not differ significantly by reducing titers to p =0.326). The difference in the anti-A and anti-B titers at 14th day posttransplant was not found to be clinically significant ( p =0.19). Conclusion With an average of 4–5 TPE procedures pretransplant and 2–3 TPE procedures posttransplants, ABO-incompatible renal transplantations can be successfully accomplished.

ABO-incompatible living donor kidney transplantation without post-transplant therapeutic plasma exchange.

Blood group incompatibility remains a significant barrier to kidney transplantation. Approximately, one-third of donors are blood group incompatible with their intended recipient. Options for these donor-recipient pairs include blood group incompatible transplantation or kidney paired donation. However, the optimal protocol for blood group incompatible transplantation is unknown. Protocols differ in techniques to remove ABO antibodies, titer targets, and immunosuppression regimens. In addition, the mechanisms of graft accommodation to blood group antigens remain poorly understood. We describe a blood group incompatible protocol using pretransplant therapeutic plasma exchange (TPE), high-dose intravenous immunoglobulin, and rituximab in addition to prednisone, mycophenolate mofetil, and tacrolimus. In this protocol, we do not exclude patients based on a high initial titer and do not implement post-transplant TPE. All 16 patients who underwent this protocol received a living donor transplant with 100% patient and graft survival, and no reported episodes of antibody-mediated rejection to date with a median follow-up of 2.6 years (range 0.75-4.7 years). We conclude that blood group incompatible transplantation can be achieved without post-transplant TPE.

Anti-ABO Specific Assay Variability Affects Antibody Removal in ABO Incompatible Kidney Transplantation (ABOiKTx) - UK Multicentre Study.

INTRODUCTION: ABOiKTx outcomes are reported better outcomes in single centres than in registry data. Intracentre and intercentre variability in ABO blood group antibody titres has been reported without clinical correlate. In a multi-centre observational study, we report the clinical outcomes and anti-ABO titre variations between centres and the impact on clinical practice. METHODS: 100 patients recruited received an ABOiKTx and data and samples were collected prospectively and analysed by blood group and extracorporeal antibody treatment (EART). Samples were analysed locally and central samples were retrospectively analysed. A single technician undertook analysis of all samples, initially demonstrating excellent reproducibility within same red cell batch; using different batches; freeze thaw repeats and on different days. RESULTS: Patient and graft survival at 1 year were 99% and 94% respectively. 70 patients were blood group ‘O’. 36 were pre-emptive transplants and 86 were 1st transplants. 80 patients had rituximab for induction. 55 patients had immunoadsorption(IA) and 31 had plasma exchange (PEx). There was no difference in clinical outcomes between IA and PEx in graft survival (Figure 1A). 29 patients experience acute rejection with 4 with antibody-mediated rejection with more rejection in blood group B recipients(Figure1B). CMV and BK nephropathy occurred in 3 and 5 patients respectively. ABO titres were higher in local assays in PEx cohort, and received more EART, however when analysed centrally, there was no significant difference in ABO titres between IA and PEx.Figure: No Caption available.CONCLUSION: In the ABOUT-K study 1 year patient and graft survival approach UK antibody compatible live donor outcomes. It is possible to minimise intra-centre variability in ABO-Ab titre measurement. This is an important intermediate goal in permitting multi-centre study and outcome optimisation in ABOi kidney transplantation.

ABO Incompatible Renal Transplantation Without Protocol Post Transplant TPE: Preliminary Results of a Pilot Study.

Background: ABOi renal transplantation is an increasingly practiced method of expanding the kidney donor pool but there is little analysis of the protocols used. Although there is substantial variation in the desensitization regimes, most incorporate protocol post transplant ABO antibody removal with therapeutic plasma exchange (TPE). We recently established an ABOi renal transplant desensitization regime without protocol post transplant TPE and report here the preliminary results. Methods: 8 patients entered into our ABOi program between January 2012 and December 2013. Data were analyzed to determine the number of TPE to achieve target pre transplant ABO antibody titres of < 1:16, ABO antibody titres post transplant, graft survival, graft function and rejection rate. Results: Median baseline ABO titres was 1:128 and all patients achieved target pre transplant ABO titres of < 1:16 after a median of 4 exchanges. Median follow up was 13 months with all patients maintaining ABO titres of < 1:16 at follow up with no protocol post transplant TPE. There was 1 case (12.5%) of acute cellular rejection which was reversed with steroids but none had antibody mediated rejection. Graft survival was 100% with current median serum creatinine 92umol/L.Table: No Caption available.Conclusions: Our preliminary results of 8 consecutive patients suggest that protocol post transplant TPE may not be necessary for maintaining suppression of ABO antibody titres especially in the critical immediate post transplant period. In addition to reducing the cost of ABOi transplants, the risk of overimmunosuppression is also reduced if protocol post ABOi transplant TPE can be avoided.

Role of plasmapheresis in ABO-incompatible renal transplantation

BackgroundThousands of patients with chronic renal failure die yearly and are unable to have a kidney transplant due to the severe shortage of donors. Therapeutic plasma exchange (TPE) is performed to remove ABO antibodies and permit ABO-incompatible (ABO-I) kidney transplants, but there is only limited research within this area and a lack of standardized protocols for TPE. This article reviews the literature to provide a historical perspective of TPE for ABO-I kidney transplantation and also provides the Johns Hopkins Hospital protocol with a focus on both titers and TPE. Study design and methodsThe TPE treatment plan is based on ABO titers with the goal of a titer of 16 or less at the anti-human globulin (AHG) phase before surgery. Pretransplant therapy consists of every-other-day TPE followed immediately by cytomegalovirus hyperimmune globulin. ABO antibody titers are closely monitored before and after transplantation. After transplantation, TPE therapy is performed for all patients to prevent rebound of anti-A and anti-B titers until tolerance or accommodation occurs. The TPE is discontinued and reinstituted based on the clinical criteria of creatinine levels, biopsy results, and ABO titer. ResultsFifty-three ABO-I kidney transplants have been completed with no episodes of hyperacute antibody-mediated rejection (AMR), and only three episodes of AMR. One-year death-censored graft survival is 100% and patient survival is 97.6%. ConclusionWhile randomized clinical trials are needed to evaluate the optimal method and protocol to remove ABO antibodies, the current literature and our results indicate a critical role for TPE in ABO-I renal transplantation.

Antibody Removal Before ABO-Incompatible Renal Transplantation: How Much Plasma Exchange Is Therapeutic?

ABOi transplantation is an accepted method of expanding the kidney donor pool but there is little analysis of the protocols used. We established an ABOi programme utilising leukocyte depletion, tacrolimus, TPE and IvIg. There are few reports in the literature on the success rates of antibody removal protocols or relating to patients in whom antibody removal fails. The purpose of this study was to define the likelihood of achieving transplantation depending on ABO antibody titers. 56 patients entered our ABOi program. Data were analysed to determine the likelihood of achieving transplantation, ABO antibody titre prior to antibody removal and amount of TPE required to achieve transplantation. The median antibody titer was 1:64 (Range 0-1:1024). Transplantation proceeded when the ABO titer reached ≤1:4. 51/56 (91%) patients achieved transplantation after 8.3±5 TPE. Five patients with high ABO titers were not transplanted despite extensive TPE. The number of TPE required to reach an ABO titer of ≤1:4 correlates best with pre-treatment IgG titers. This is the first study to demonstrate a cut off titer for entry in to the ABO incompatible program using the relationship between ABO titer and amount of TPE required to reach transplantation. We now tailor the antibody removal protocol prior to transplantation and have introduced a cut-off entry titer to the program (≤1:256), because of the unacceptable risk of exposing patients with higher titers to long-lasting immunosuppression and costly, prolonged, courses of TPE without the guarantee of successful transplantation. Patients whose ABO titer exceeds the cut-off are counselled and offered alternative routes to transplantation.