Anti-blood Group Antibodies Research Articles

The association of ABO blood group distribution and clinical characteristics in patients with SARS-CoV-2

SARS-COV-2, the novel severe acute respiratory syndrome coronavirus, has become a life-threatening public health crisis. This kind of pandemic is frightening the world with clinical, psychological, and emotional distress and leading to an economic slowdown. To explore any association between the ABO blood type and the susceptibility to coronavirus disease 2019 (COVID-19), we compared ABO blood group distribution among 671 COVID-19 patients with the local control population. The study was conducted in Blood Bank Hospital in Erbil, Kurdistan Region, Iraq. The ABO-typed blood samples were obtained from 671 patients infected with SARS-CoV-2 between February and June 2021. Our results demonstrated that the risk of SARS-COV-2 was higher for patients with blood group A than those with not-A blood type patients. Of the 671 patients with COVID-19, 301 had type A (44.86%), 232 had type B (34.58%), 53 had type AB blood (7.9%), and 85 had type O (12.67%). We concluded that the Rh-negative blood type has a protective effect on SARS-COV-2. Our results also indicate that the decreased susceptibility of individuals with blood group O and the increased susceptibility of individuals with blood group A to COVID-19 could be linked to the presence of natural anti-blood group antibodies, particularly anti-A antibody, in the blood. However, there might be other mechanisms that require further study.

W265 Application of geometric mean criteria to anti-blood group antibody proficiency testing in Korean external quality assurance program

W265 Application of geometric mean criteria to anti-blood group antibody proficiency testing in Korean external quality assurance program

Application of Geometric Mean Criteria for Anti-Blood Group Antibody Proficiency Testing in the Korean External Quality Assurance Program

Application of Geometric Mean Criteria for Anti-Blood Group Antibody Proficiency Testing in the Korean External Quality Assurance Program

Evaluation of the Bactericidal Activity of Galectins.

Over a century ago, Karl Landsteiner discovered that blood group antigens could predict the immunological outcome of red blood cell transfusion. While the discovery of ABO(H) blood group antigens revolutionized transfusion medicine, many questions remain regarding the development and regulation of naturally occurring anti-blood group antibody formation. Early studies suggested that blood group antibodies develop following stimulation by bacteria that express blood group antigens. While this may explain the development of anti-blood group antibodies in blood group-negative individuals, how blood group-positive individuals protect themselves against blood group-positive microbes remained unknown. Recent studies suggest that several members of the galectin family specifically target blood group-positive microbes, thereby providing innate immune protection against blood group antigen-positive microbes regardless of the blood group status of an individual. Importantly, subsequent studies suggest that this unique form of immunity may not be limited to blood group expressing microbes, but may reflect a more generalized form of innate immunity against molecular mimicry. As this form of antimicrobial activity represents a unique and unprecedented form of immunity, we will examine important considerations and methodological approaches that can be used when seeking to ascertain the potential antimicrobial activity of various members of the galectin family.

Novel double-filtration plasmapheresis preserves fibrinogen while removing immunoglobulin-G antibodies before ABO blood type-incompatible kidney transplantation

BackgroundRemoval of anti-blood group antibodies is important for successful ABO-incompatible kidney transplantation (ABOi-KTx). Double-filtration plasmapheresis (DFPP) using albumin solution removes antibodies effectively. However, fibrinogen is largely removed resulting in hemostatic failure. Herein, we designed an altered combination of plasma membranes in DFPP (novel DFPP, nDFPP) to retain more fibrinogen while removing IgG, and assessed its efficacy and safety compared with conventional DFPP (cDFPP).MethodsConsecutive ABOi-KTx recipients (from 2015 to 2018) were enrolled. For the first membrane, we used Cascadeflo EC-50W in nDFPP and Plasmaflo OP-08W in cDFPP, and Cascadeflo EC-20W as the second membrane in both modalities. Removal rates (RR) of IgG, IgM and fibrinogen per DFPP session, and adverse events were compared with historical control patients who underwent cDFPP before ABOi-KTx, between 2006 and 2015.ResultsnDFPP and cDFPP groups included 12 and 23 cases, respectively. nDFPP was inferior to cDFPP in RR of IgG and IgM. nDFPP was also inferior to cDFPP in the decline in anti-blood group IgG and IgM antibody titers. However, fibrinogen was more preserved in nDFPP compared with cDFPP, indicating that nDFPP has more selective removal properties (median RR of IgG, IgM, and fibrinogen: 62.1%, 15.7% and 37.6%, respectively, in nDFPP; and 74.5%, 85.0% and 76.6%, respectively, in cDFPP). In the comparison of hemostatic function among the patients who had arteriovenous fistula for hemodialysis, prolonged hemostasis (> 20 min) at the cannulation site was significantly less frequently observed in nDFPP group (1 in 9 cases, 9.1%) than in cDFPP group (all 18 cases, 10%, p < 0.0001).ConclusionsnDFPP preserves fibrinogen while removing anti-blood type IgG antibodies before ABOi-KTx.

ABO-Incompatible Kidney Transplantation in India: A Single-Center Experience of First Hundred Cases.

Aim:ABO-incompatible (ABOi) kidney transplantation overcomes immunological barrier of blood group incompatibility. There have been very few published experiences of ABOi kidney transplantation from India. We present our single-center experience of the first hundred ABOi kidney transplants.Material and Methods:This is a single-center retrospective study of consecutive first hundred ABOi kidney transplant with at least 6 months of follow-up.Results:During the study period (2011–2020), a total of 121 ABOi kidney transplants were performed. Of these, first hundred patients were analyzed. Median follow-up duration was 33 (10–101) months. Mean recipient and donor age were 41.5 ± 13 and 47.68 ± 11.25 years, respectively. Mean HLA mismatch was 4 ± 1.5. Median baseline anti-blood group antibody titer was 128 (2–1024). Most common recipient blood group was O. Patient and death censored graft survival was 93% and 94%, respectively, at median follow-up of 33 months. Biopsy-proven acute rejection (BPAR) rate was 17% with acute antibody-mediated rejection being 3%. Rate of infection was 37%, most common being urinary tract infection.Conclusion:ABOi kidney transplant patients had acceptable patient and graft survival as well as BPAR rates. With current preconditioning protocol, infection rate was high.

P1756ANTI-ABO ANTIBODY- VERSUS ANTI-HLA ANTIBODY-INDUCED ANTIBODY MEDIATED REJECTION IN ABO-INCOMPATIBLE KIDNEY TRANSPLANT PATIENTS: RELATIVE INCIDENCE AND PHENOTYPE DIFFERENCE

Abstract Background and Aims Antibody-mediated rejection(AMR) in ABO incompatible(ABOi) kidney transplant(KT) patients can either be due to donor-specific anti-HLA antibody(DSA) or anti-blood group antibody. The relative frequency and possible phenotype difference of these two types of AMR in ABOi KT patients have not been reported. Method Of 111 ABOi KT patients between 2007 and 2019 in our center, 15(13.5%) patients developed acute AMR diagnosed by indication biopsy. Since there is no histologic distinction between DSA- and anti-ABO-induced AMR, we assumed the causative antibody in each case based on anti-ABO level and DSA, measured in serum collected at the time of AMR. Results Of these 15 cases of acute AMR, 5 were attributable to anti-ABO(ABO-AMR) since anti-ABO titer was higher (≥16) and DSA was undetectable at the time of rejection. Five cases were attributable to DSA(DSA-AMR) since DSA was detectable and anti-ABO was lower during rejection. Another 3 cases with lower anti-ABO titer and undetectable DSA were also assumed to be DSA-induced, since this low level of anti-ABO is unlikely to cause rejection and DSA can be undetectable in DSA-induced AMR by adsorption of Ab on graft, as frequently seen in ABO-compatible patients Two cases with both higher anti-ABO titer and detectable DSA was regarded as undetermined. The onset of acute AMR was within 2 weeks in all cases(median 7.0 days) and comparable between DSA- and ABO-AMR. Initial anti-ABO titer was also not statistically different; median(range) 256(64-4096) in ABO-AMR and 64(16-256) in DSA-AMR. All the 5 patients with ABO-AMR had negative PRA before KT, whereas 5 of 8 patients with DSA-AMR had positive PRA before KT, and two DSA-AMR patients had preformed DSA before KT. There was no difference in peak creatinine and response to treatment. All the AMR were recovered by treatment and no graft was lost to rejection. No patient with ABO-AMR developed chronic AMR whereas one of DSA-AMR patients developed chronic AMR. Conclusion In summary, among 15 cases of acute AMR, 5 were ABO-AMR, 8 were DSA-AMR and 2 were undetermined. There was no difference in clinical feature between DSA- and ABO-AMR. No patient with ABO-AMR developed chronic AMR.

A comparison of the automated blood bank system IH-500 and manual tube method for anti-blood group antibody titration: a quantitative approach

BackgroundAnti-blood group antibody titers (ABTs) reported in titer values are variable depending on the testing method used. The introduction of new test methods such as automated methods requires proper method comparison. In this study, the automated blood bank system and manual tube method for ABT were compared using a log-transformed dataset to evaluate the alternative statistical approach. MethodsABT was conducted using specimens referred for solid organ transplantation. Methods for comparison were conventional manual tube method and IH-500 automated blood bank system using column agglutination (CAT). Criteria for agreement were exact match and 1-titer match. Measured titer values were log-transformed into interval scale for Deming regression analysis. ResultsFrom the comparison of the tube and CAT methods using titer values and the two criteria, the exact and 1-titer match were 15.9–41.5 % and 65.9–97.6 %, respectively. Deming regression was used to demonstrate the presence of both proportional and constant difference between the two methods. ConclusionThe method comparison using conventional statistical approaches had limits due to the semi-quantitative value of the test. Log-transformed interval scale values for comparison were useful for interpretation of method comparison datasets. This alternative statistical approach could contribute to a more accurate comparison between assays and standardization of ABT testing.

Retrospection of Anti-Blood Group Antibody Proficiency Testing Data Using the Geometric Mean and Standard Deviation.

We reanalyzed the data from proficiency testing (PT) to assess the effect of the geometric mean in the statistical analysis of immunohematologic data. Using the five most recent anti-blood group antibody titer participant summary results, the geometric mean (GM) ±2 × geometric standard deviation (GSD) was used as the comparative consensus criterion to mode ±2 titers. Using the PT evaluation criterion of mode ±2 titers, the mean percentages of participants with acceptable results were 97.5% and 97.8% for anti-A and anti-D, respectively. When applying GM ±2 GSD, the mean percentages of acceptable results were 96.1% (anti-A) and 96.1% (anti-D). The percentages of responses included in each consensus criterion were lower using GM ±2 GSD, with a few exceptions. Geometric means are more robust and precise in visualizing the central tendency. This method can improve the statistical robustness of PT evaluations.

Complement activation and long-term graft function in ABO-incompatible kidney transplantation.

BACKGROUNDABO-incompatible and ABO-compatible kidney transplantation are equivalent in terms of short-term graft and patient survival. This is thought to be the result of ABO-incompatible graft accommodation, which occurs when anti-blood group antibodies re-occur after transplantation but somehow do not yield their detrimental effect. The underlying mechanism is unclear, but one of the hypotheses is that this is the result of complement inhibition. Since virtually all ABO-incompatible graft biopsies are C4d positive, this complement inhibition must occur somewhere in the complement cascade after the formation of C4d has already taken place, but where exactly is unclear. It is also unclear whether complement inhibition is complete. Incomplete accommodation could explain why recent studies have shown that long-term graft function in ABO-incompatible transplantation is somewhat inferior to ABO-compatible kidney transplantation.AIMTo unravel the relationship between pre-transplant anti-ABO antibodies, complement activation, and long-term graft function.METHODSWe included all 27 ABO-incompatible transplantations that were performed between 2008 and 2013 at the Academic Medical Center Amsterdam and the University Medical Center Groningen. For each ABO-incompatible transplantation, we included four ABO-compatible controls matched by age, sex, and transplantation date.RESULTSGraft and patient survival were not significantly different. The slope of kidney function during five-year follow-up was also not significantly different, but ABO-incompatible recipients did have a lower kidney function at three months (creatinine clearance 58 vs 69 mL/min, P = 0.02, Modification of Diet in Renal Disease 46 vs 52 mL/min/1.73 m2, P = 0.08), due to a high rate of early rejection (33% vs 15%, P = 0.03), mostly T-cell mediated. Pre-transplant anti-ABO IgG titers were positively correlated with C5b-9 staining, which itself was positively correlated with the occurrence of T-cell mediated rejection. This may be the result of concurrent C5a formation, which could function as a costimulatory signal for T-cell activation.CONCLUSIONCo-stimulation of T-cell activation by ongoing complement activation by anti-ABO antibodies may be responsible for an impaired long-term graft function in ABO-incompatible kidney transplantation.

Accommodation in ABO-incompatible organ transplants.

Accommodation refers to a condition in which a transplant (or any tissue) appears to resist immune-mediated injury and loss of function. Accommodation was discovered and has been explored most thoroughly in ABO-incompatible kidney transplantation. In this setting, kidney transplants bearing blood group A or B antigens often are found to function normally in recipients who lack and hence produce antibodies directed against the corresponding antigens. Whether accommodation is owed to changes in anti-blood group antibodies, changes in antigen or a change in the response of the transplant to antibody binding are critically reviewed and a new working model that allows for the kinetics of development of accommodation is put forth. Regardless of how accommodation develops, observations on the fate of ABO-incompatible transplants offer lessons applicable more broadly in transplantation and in other fields.

ABO-incompatible renal transplantation: The journey so far on a road less traveled

Introduction: ABO-incompatible (ABOi) renal transplant is the only option for patients who have neither blood group-compatible donors nor a suitable swap available. Published Indian experience of ABOi transplants has been far and few. Materials and Methods: This study was conducted across two different centers. All the consecutive ABOi renal transplants performed from November 2011 onward and who had completed at least 6 months of follow-up were included. Data were accessed retrospectively from the medical records. Results: There were fifty ABOi recipients who had completed at least 6 months of follow-up. Most common recipient blood group was group O. Median baseline antiblood group antibody titer (immunoglobulin G) was 256. Patient and death-censored graft survival were 94% and 88%, respectively, and biopsy-proven acute rejection was 22%. Acute antibody-mediated rejection was seen in 8% of the patients. Mean serum creatinine was 1.12 mg/dl at 1-month posttransplant and infection rate was 22%. Conclusion: The outcomes of ABOi transplant were acceptable and it should be promoted to bridge the demand and supply gap for renal transplant and expand the living donor pool.

Baseline anti-blood group antibody titers and their response to desensitization and kidney transplantation

In recent years, immunological barriers historically considered as absolute contraindications to transplantation are being reevaluated. One such barrier is the ABO blood group incompatibility. With better understanding of immunological mechanisms and effective various regimens for controlling it, ABO-incompatible (ABO-I) kidney transplantation is now being performed with increasing frequency. For good outcome, most important is to achieve and maintain low anti-blood group antibody titers (ABGATs). Twenty-two patients with ABO-I donors have been studied. The anti-A and anti-B antibody titers (IgG and IgM) were estimated by column agglutination technology using Automated Ortho BioVue System. For desensitization, pretransplant plasmapheresis and/or immunoadsorption and rituximab were used. ABGAT was determined before transplant and periodically after transplant. It was observed that one-third of the patients have low baseline ABGAT. In these cases with low ABGAT, transplant can be performed without any desensitization. In those with titers <1:256, rituximab (two doses of 200 mg weekly) and 3–6 sessions of plasmapheresis can bring down titers to <1:32. In those with titers >1:256, immunoadsorption may be used from the beginning to reduce ABGAT. After transplant, the titers drop to <1:8 in majority. Rise in titers to >1:64 require close observation and biopsy. If there is evidence of antibody-mediated rejection, treatment should be promptly started. Rise in titers 4–6 weeks after transplant is not associated with any graft dysfunction, and hence not of any clinical significance.

Microbial Exposure Regulates the Development of Anti-Blood Group Antibodies

Introduction: Anti-ABO antibodies represent the earliest recognized immunological barrier to transfusion and transplantation. However, despite Landsteiner's discovery of ABO blood group antigens over a century ago, the factors that regulate anti-ABO antibody formation remain relatively unknown. Anti-ABO antibodies develop spontaneously within the first few months of life, in the absence of a known antigenic exposure. However, antibody levels vary considerably between individuals suggesting that differences in exposure to environmental triggers may regulate anti-ABO antibody formation. As distinct microbes can stimulate very specific anti-carbohydrate antibodies, we hypothesized that variation in exposure to microbes that decorate themselves in ABO carbohydrates may regulate anti-blood group antibody formation. However, no model currently exists to examine the potential impact of microbial exposure on the development of naturally occurring anti-blood group antibodies.Methods: To examine the regulatory capacity of specific microbial exposure on naturally occurring antibody formation, we generated a model of ABO blood group antigens. As lower mammals do not express ABO antigens, we used recipients knocked out (KO) for the glycosyltransferase responsible for the synthesis of the carbohydrate B disaccharide (Bdis) antigen, an antigen very similar to the human blood group B antigen. Microbial flora was assessed in WT (Blood group B-like) or Bdis KO (Blood group O-like) by sequencing ribosomal DNA isolated from stool samples. Serum was assessed for Bdis reactivity at baseline and following Bdis+ microbial exposure using a glycan microarray. WT or Bdis KO recipients were transfused with Bdis+ RBCs followed by the evaluation of RBC clearance, antibody engagement and complement fixation by flow cytometry.Results: Similar to blood group O individuals, Bdis KO recipients spontaneously develop varied amounts of anti-Bdis antibodies within the first few weeks of life capable of inducing an acute hemolytic transfusion reaction following incompatible Bdis+ RBC transfusion. To determine whether specific microbial exposure is the primary regulating factor in anti-Bdis antibody formation, we separately housed Bdis KO recipients with low titer anti-Bdis antibodies, yielding an entire Bdis KO colony that never developed detectable anti-Bdis antibodies. Exposure of Bdis KO recipients that lacked detectable anti-Bdis antibodies to specific microbes that express the Bdis antigen induced robust anti-Bdis antibodies. However, the timing of microbial exposure was critical in dictating the likelihood of anti-Bdis antibody formation as younger mice produced anti-Bdis antibodies much more readily than adult mice following Bdis+ microbial exposure. Consistent with this, only Bdis KO recipients that experienced early Bdis+ microbial exposure possessed anti-Bdis antibodies with the capacity to induce an acute hemolytic transfusion reaction following Bdis+ RBC transfusion.Conclusions: These results demonstrate that Bdis KO recipients provide an attractive model to study naturally occurring antibody formation and suggest that anti-ABO antibodies are not an inevitable outcome of not expressing ABO blood group antigens. Instead, naturally occurring antibody formation appears to be temporally regulated by specific microbial exposure. As younger Bdis KO recipients developed antibody more readily than older Bdis KO recipients, in addition to Bdis+ microbial exposure, the actual timing of exposure appears to be a key regulator of anti-Bdis antibody formation. Thus variations in an individual's microbiota, particularly during early immunological development, likely dictate the level of anti-ABO antibody formation. As a result, intentional manipulation of an individual's microbial flora may provide a unique and previously unrecognized approach to prevent anti-ABO(H) antibody development in patients requiring transplantation or chronic transfusion. DisclosuresNo relevant conflicts of interest to declare.

ABO-incompatible renal transplantation in developing world - crossing the immunological (and mental) barrier.

ABO incompatibility has been considered as an important immunological barrier for renal transplantation. With the advent of effective preconditioning protocols, it is now possible to do renal transplants across ABO barrier. We hereby present a single center retrospective analysis of all consecutive ABOi renal transplants performed from November 2011 to August 2014. Preconditioning protocol consisted of rituximab, plasmapheresis and intravenous immunoglobulin (IVIG) and maintenance immunosuppression consisted of tacrolimus, mycophenolate sodium, and prednisolone. The outcome of these ABOi transplants was compared with all other consecutive ABO-compatible (ABOc) renal transplants performed during same time. Twenty ABOi renal transplants were performed during the study period. Anti-blood group antibody titer varied from 1:2 to 1:512. Patient and graft survival was comparable between ABOi and ABOc groups. Biopsy proven acute rejection rate was 15% in ABOi group, which was similar to ABOc group (16.29%). There were no antibody-mediated rejections in ABOi group. The infection rate was also comparable. We conclude that the short-term outcome of ABOi and ABOc transplants is comparable. ABOi transplants should be promoted in developing countries to expand the donor pool.

Response of antiblood group antibodies to desensitization procedures & kidney transplantation

Response of antiblood group antibodies to desensitization procedures & kidney transplantation

ABO Incompatible Renal Transplantation Without Antibody Removal Using Conventional Immunosuppression Alone

ABO incompatible living donor renal transplantation (ABOi) can achieve outcomes comparable to ABO compatible transplantation (ABOc). However, with the exception of blood group A2 kidneys transplanted into recipients with low titer anti-A antibody, regimens generally include antibody removal, intensified immunosuppression and splenectomy or rituximab. We now report a series of 20 successful renal transplants across a range of blood group incompatibilities using conventional immunosuppression alone in recipients with low baseline anti-blood group antibody (ABGAb) titers. Incompatibilities were A1 to O (3), A1 to B (2), A2 to O (2), AB to A (2), AB to B (1), B to A1 (9), B to O (1); titers 1:1 to 1:16 by Ortho. At 36 months, patient and graft survival are 100%. Antibody-mediated rejection (AbMR) occurred in one patient with thrombophilia and low level donor-specific anti-HLA antibody. Four patients experienced cellular rejection (two subclinical), which responded to oral prednisolone. This series demonstrates that selected patients with low titer ABGAb can undergo ABOi with standard immunosuppression alone, suggesting baseline titer as a reliable predictor of AbMR. This reduces morbidity and cost of ABOi for patients with low titer ABGAb and increases the possibility of ABOi from deceased donors.

ABO-Compatible Retransplantation After ABO-Incompatible Infant Heart Transplantation: Absence of Donor Specific Isohemagglutinins

Implementation of ABO-incompatible (ABOi) pediatric heart transplantation has contributed to significant reduction in the mortality of infants on the waiting list, without increasing the risk of rejection. This has been attributed to the immature and therefore not fully competent immune system in this population group, which results in lower production of isohemagglutinins compared to older children and adults. Serial evaluations of isohemagglutinin titers in infants revealed cases with absence of donor specific anti-blood group antibodies. However, it is currently unknown whether continuous exposure to donor antigens is necessary to prevent formation of donor specific isohemagglutinins (DSI) in recipients. We are reporting a case of an infant who underwent ABOi heart transplantation, with no evidence of DSI even 4 years after ABO-compatible retransplantation. Hence, temporary exposure to donor antigens in infants may contribute to permanent absence of donor specific anti-blood group antibodies, suggesting the possibility of induced permanent B cell tolerance.

Evaluation of the bactericidal activity of galectins.

Over a century ago, Karl Landsteiner discovered that blood group antigens could predict the immunological outcome of red blood cell transfusion. While the discovery of ABO(H) blood group antigens revolutionized transfusion medicine, many questions remain regarding the development and regulation of naturally occurring anti-blood group antibody formation. Early studies suggested that blood group antibodies develop following stimulation by bacteria that express blood group antigens. While this may explain the development of anti-blood group antibodies in blood group negative individuals, how blood group positive individuals, who cannot generate anti-blood group antibodies, protect themselves against blood group positive microbes remained unknown. Recent studies suggest that several members of the galectin family specifically target blood group positive microbes, thereby providing innate immune protection against blood group antigen positive microbes regardless of the blood group status of an individual. Importantly, subsequent studies suggest that this unique form of immunity may not be limited to blood group expressing microbes, but may reflect a more generalized form of innate immunity against molecular mimicry. As this form of antimicrobial activity represents a unique and unprecedented form of immunity, we will examine important considerations and methodological approaches that can be used when seeking to ascertain the potential antimicrobial activity of various members of the galectin family.

Predicting the Origins of Anti-Blood Group Antibody Specificity: A Case Study of the ABO A- and B-Antigens.

The ABO blood group system is the most important blood type system in human transfusion medicine. Here, we explore the specificity of antibody recognition toward ABO blood group antigens using computational modeling and biolayer interferometry. Automated docking and molecular dynamics simulations were used to explore the origin of the specificity of an anti-blood group A antibody variable fragment (Fv AC1001). The analysis predicts a number of Fv-antigen interactions that contribute to affinity, including a hydrogen bond between a HisL49 and the carbonyl moiety of the GalNAc in antigen A. This interaction was consistent with the dependence of affinity on pH, as measured experimentally; at lower pH there is an increase in binding affinity. Binding energy calculations provide unique insight into the origin of interaction energies at a per-residue level in both the scFv and the trisaccharide antigen. The calculations indicate that while the antibody can accommodate both blood group A and B antigens in its combining site, the A antigen is preferred by 4 kcal/mol, consistent with the lack of binding observed for the B antigen.