anti-B Antibody Titer Research Articles

Intentional ABO-incompatible heart transplantation: A case report of 2 adult patients

In 2009, we started to screen all patients on the heart transplant waiting list for the presence of blood group anti-A or anti-B antibodies. From our experience with ABO-incompatible kidney transplantation, we know that transplantation can safely be performed if the antibody level is reduced to a titer of immunoglobulin G (IgG) 1:8. We decided to accept all patients with anti-A or anti-B antibody titer ≤1:8 for ABO-incompatible heart transplantation without any special pre-treatment and patients with antibody titers of IgG 1:16 and 1:32, provided 1 apheresis session could be performed immediately before transplantation. We found 6 of 13 patients were suitable for this program, and 2 ABO incompatible patients underwent successful transplantation with a follow-up of 1 year. In heart transplant candidates where there are problems obtaining a compatible heart and who are not suitable for ventricular assist device support, ABO-incompatible heart transplantations can be considered using our protocol, provided that the levels of anti-A or anti-B antibodies are low.

Selective capture of anti‐A antibodies from human blood using a novel integrated bead and hollow fiber module

Anti-A/B antibody removal from blood in the peritransplantation period facilitates ABO-incompatible transplantation and significantly increases the donor pool. We have been developing an anti-A/B immunoadsorption device (BSAF), compatible with whole blood perfusion. The BSAF is based on integrated microfiltration hollow fibers with antibody capturing beads uniformly distributed within the fiber interstitial space. In this study we fabricated BSAF prototypes, appropriately scaled down from a conceptual clinical scale device. We then, for the first time, measured the time course of anti-A capture from blood samples recirculating through the scaled down BSAF devices. We observed a significant reduction in IgM (96% ± 5%, n = 5, p < 0.001), and IgG (81% ± 18%, n = 5, p < 0.05) anti-A antibody titers within 2 h. We did not observe a significant change between the initial and final values of hematocrit, total plasma protein concentration, plasma free hemoglobin concentration, and anti-B antibody titer over five experiments. In conclusion we showed that the BSAF modules selectively removed anti-A antibodies from blood in a simple one step process, without requiring a separate plasmapheresis unit.

Distribution of ABO Blood Group Antibody Titers in Pediatric Patients Awaiting Renal Transplantation

Blood group-incompatible transplantation is one strategy used when a potential recipient does not have a compatible living donor. Current practice includes desensitization strategies to reduce antibody titers. However, when antibodies are low, in cardiac transplantation in neonates for example, no desensitization is required. This study is the first to examine the distribution of ABO blood group antibody titers in a population of pediatric patients on the deceased-donor renal transplantation waiting list. All patients from two pediatric nephrology centers active on the national deceased-donor waiting list had antibody titers (total immunoglobulin load) measured. A simulation modeling the effect of allocating blood group-incompatible deceased-donor kidneys to those patients with titers of 16 or lower was developed. Twenty-four children were screened; eight (33.3%) had titers of either anti-A or anti-B antibodies of 8 or lower. A further three (12.5%) had either an anti-A or anti-B antibody titer of 16. Blood group A or B patients had lower antibody levels than blood group O patients. In blood group O patients, levels of anti-A antibodies were higher than anti-B antibodies (Wilcoxon signed rank test, P=0.028). The simulation model showed that a change in organ allocation policy would increase pediatric transplant activity by 2.2% and reduce the median waiting time for a transplant. This allocation strategy may be of particular benefit to those pediatric patients who have been on the deceased-donor waiting list for a long time or those with a high calculated reaction frequency.

ABO-Incompatible Kidney Transplantation: First Cases in Turkey

IntroductionABO compatibility has been believed to be necessary in kidney transplantation (Ktx) to prevent acute antibody-mediated rejection. However, developments in immunosuppression and immunoadsorption techniques have overcome acute antibody-mediated rejection caused by ABO incompatibility. Herein, we have presented the first ABO-incompatible Ktx cases in Turkey. All recipients did not have an ABO-compatible donor but presented significant dialysis inadequacy due to vascular access problems. MethodFive dialysis patients with blood groups O or B underwent kidney transplantation from living related donors of blood group type A1 or AB between march 23, 2007 and August 16, 2007. All patients received Rituximab (375 mg/m2) at 3–4 weeks before the Ktx. Additionally, we started tacrolimus (0.15 mg/kg), mycophenolate mofetil (2 × 1 g), and simvastatin (1 × 20 mg) 1 week before the operation. Immunoadsorption therapy employing a specific filter (Glycosorbs) to remove anti-A or anti-B antibodies was continued until the titers were <1/4. After the Ktx, we again performed immunoadsorption if the anti-A or the anti-B antibody titer was >1/8 during the first postoperative week and >1/16 at the second postoperative week. We used 2 standard hemodialysis machines with a connection line to perform immunoabsorption and dialysis during the same session. ResultsAcute humoral and cellular rejection was not detected. During the follow-up 1 patient was lost due to a cardiovascular complication. Mean creatinine level was 1.1 ± 0.3 mg/dL. These first ABO-incompatible transplantation cases in Turkey suggest that this source may represent an effective approach to overcome the organ shortage.

Immune hemolysis after fludarabine-based reduced intensity conditioning and allogeneic PBSC transplantation for CML with minor ABO incompatibility

Dear Editor, Fludarabine is commonly used in reduced intensity conditioning (RIC) regimens and has been linked to immune hemolysis [1, 2]. We report the first case of severe immune hemolysis in the fludarabine-based RIC allogeneic peripheral blood stem cell transplantation (PBSCT) for chronic myelogenous leukemia (CML) in the setting of minor ABO incompatibility. A 47-year-old woman diagnosed with CML underwent allo-PBSCTwith an HLA-matched related donor in February 2007, while in the accelerated phase. Conditioning consisted of busulfan, 2 mg/kg/day (days −6 and −5), fludarabine, 30 mg/m2/day (days −6 to −2), and anti-thymoglobulin, 10 mg/kg/day (days −4 to −1). GVHD prophylaxis consisted of cyclosporine, 5 mg/kg/day, and mycophenolate mofetil, 45 mg/kg/day. There was minor ABO incompatibility between the donor (O Rh-positive) and the recipient (B Rhpositive). The donor's anti-B antibody titer in saline test tube at 37°C was 1:8 IgG. The conditioning regimen and stem cell infusion were both uneventful. Eight days after PBSCT, she developed mucocutaneous pallor, asthenia, and nausea. Laboratory studies indicated severe hemolysis with a drop in the hemoglobin level, an increase in the serum bilirubin and lactic dehydrogenase (LDH) levels, and complete disappearance of haptoglobin (graph). Peripheral blood contained spherocytes. No fragmentation was observed. Renal function and clotting studies were normal. Thorough microbiological studies were negative. Investigations for hepatitis A, B, and C viruses, VDRL, HTLV I and II, HIV, HSV, adenovirus, parvovirus, EBV, HHV-6, cytomegalovirus, and toxoplasmosis were negative. Computed tomography (CT) of the chest and sinuses was normal, and CT of the abdomen showed only splenomegaly. Serological screening for autoimmune diseases was negative. None of the medications she was receiving was known to cause hemolysis. The direct antiglobulin test (DAT) was positive for IgG and C3d. Recipient red blood cells (RBC) were repeatedly B positive. The serum anti-B antibody titer in saline test tube at 37°C was 1:2 IgG. Antibodies eluted from the patient's RBCs showed pan-agglutination against group O antibody panel cells. Allo-antibodies were excluded by adsorption studies. The diagnosis of immune intravascular hemolysis was established. The lowest recorded hemoglobin level was 5 g/dl, and the highest levels of bilirubin and LDH were respectively 7 mg/dl (normal, 0.2 to 1.0 mg/dl) and 791 IU/ l (normal, 120 to 200 IU/l). Methylprednisolone, 2 mg/kg/day intravenously, was administered from day +8 for five consecutive days and was then gradually withdrawn over 2 months. The hemoglobin level improved rapidly, and the hemolysis panel normalized (Fig. 1). Repeated anti-B titers in saline test tube at 37°C were respectively 1:8 and 1:16 on days +11 and +14. On day +14, the DAT was negative, and the patient's blood group was O Rh positive. She received a total of six units of type O Rhpositive packed red blood cells from days +10 to +13, and no further transfusions were necessary. VNTR analysis on R. Calixto : F. Ostronoff :M. Ostronoff :A. Sucupira : R. Florencio :A. P. S. Maior :M. C. Domingues Hematology and Bone Marrow Transplantation Unit, Real-Hospital Portugues, Recife, PE, Brazil

Experience With Laparoscopic Splenectomy for ABO-Incompatible Living Renal Transplantation Without Plasmapheresis

A 25-year-old male, blood type A, was admitted to our hospital for renal transplantation from his father of AB blood type. Before transplant, we performed laparoscopic splenectomy. The serum anti-B antibody titer fell from 1:8 to 1:2. Therefore, plasmapheresis was not performed. The total ischemic time was 80 minutes. Five immunosuppressive agents, including tacrolimus, mycophenolate mofetil, prednisolone, basiliximab, and deoxyspergualine, were administered in the initial period. On the 47th day, value of cytomegalovirus antibody, which was routinely measured, became positive. Hence, we administered ganciclovir, with a fall in antibody. Sixty-five days after transplant, he was discharged with a serum creatinine of 1.0 mg/dL. We concluded that it was possible to perform ABO-incompatible renal transplantation with no need for plasmapheresis or rituximab.

ABO-incompatible heart transplantation: a perfusion strategy.

Infants with fatal cardiac disease often die awaiting transplantation because of the shortage of donor hearts. The Hospital for Sick Children (HSC), Toronto, Canada, has researched and applied the concept of crossing the blood group compatibility barrier. Heart transplantation at HSC unrestricted by ABO compatibility greatly contributed to decreasing the mortality rate among infants on the waiting list from 58% to 10%. From January 1996 to January 2002, 16 infants less than 14 months of age received ABO-incompatible heart transplants at our institution. The cardiopulmonary bypass (CPB) circuit is primed with additional volume to replace the patient's blood volume. Packed red blood cells (PRBC) used in priming must be ABO-compatible with the recipient. All plasma components and platelets must contain no anti-A or anti-B antibodies to donor or recipient. CPB is initiated and the patient's venous blood is collected into a transfusion bag and sent to the blood bank. The total amount collected should be one and a half to two times the patient's blood volume. The plasma is separated and discarded, returning only the PRBC, thus reducing the concentration of circulating antibodies to blood group antigens. Our team has experienced an 87% survival rate with this technique. The success is believed to be associated with the recipients' immunologic immaturity. Newborns do not produce isohemagglutinins, and serum anti-A and anti-B antibody titers usually remain low until 12-14 months of age. The complement system is not fully developed, therefore, the mediators of hyperacute rejection are absent during early infancy. Heart transplantation unrestricted by the need for ABO compatibility would effectively expand the available donor pool and decrease waiting times.

The role of maternal anti-A and anti-B antibody titers in predicting ABO hemolytic disease of the newborn

A study has been conducted on 268 blood group O delivering mothers and their related blood group A and B newborn infants. It reveaLed that the capability of mothers 1o produce anti-A and anti-B antibodies did not dffir significantly from each other (p > 0.05) . Ninety four (35.1Vo) ofthe newborns developed potentionaljaundice while the others did not. To predict the birth ofa baby with potential jaundice, a maternal anti-A or anti-B antibody titer of > l/256 was considered to be the cut-offpoint with a sensitivity and specificity of S3.33VoandTS.2lVorespectivelyandapositivepredictivevalueofTg.2TVoandanegativepredictivevalueof 17.57Va. Ifthematemal anti-Aoranti-Bantibody titerwas>l/256theriskforgivingbirthofababywithpotentialjaundicerosesignificantlylStimescompared to those with titers of < 1/256 (OR 18,64 ; CI 95Vo = 6.18-56.18).

ｍｉｎｏｒ ＡＢＯ不適合骨髄移植後の正常同種凝集素および糖転移酵素の変化

Changes in anti-A and anti-B antibody titer and A- and B-glicosyltransferase activity were analyzed in five patients after minor ABO-incompatible bone marrow transplantation (BMT). All patients showed complete engraftment after BMT. Shortly after BMT, blood types of recipient's erythrocytes as examined by standard agglutination techniques changed into those of the donor's erythrocytes. Using the elution method, however, recipient's erythrocyte antigens were detected on erythrocytes from three of five patients with complete engraftment after BMT. Analysis of A- and B-transferase activity in serum demonstrated that four of five patients maintained pre-BMT transferase activity. The other patient, who showed no A- or B-transferase activity after BMT, had an inhibitor to this activity. These results suggest that in patients receiving BMT, a small amount of blood antigens on erythrocytes and serum transferase activity may be derived from the patient's tissue.

ABO Incompatible Kidney Transplantation in Children

We have performed 7 pediatric kidney transplantations from living related donors of ABO incompatibility. All patients preoperatively underwent plasmapheresis with or without immunoadsorption to reduce anti-A and/or anti-B antibodies. Immunosuppression initially consisted of methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin and deoxyspergualin. At transplantation splenectomy was simultaneously performed in all patients. Median followup is 44 months (range 31 to 58). Patient and graft survival rates are 100 percent to date. There were no uncontrolled vascular rejection episodes, and post-transplant anti-A and/or anti-B antibody titers were always less than 1:32. Transplantation across the ABO blood barrier remains challenging today. However, our small series clearly shows that the preoperative reduction of ABO antibody, simultaneous splenectomy and strict immunosuppressive therapy cause successful long-term results in children.

ABO-INCOMPATIBLE RENAL TRANSPLANTATION

From recent works, it can be concluded that renal transplantation across ABO incompatibility is acceptable if no other donor is available. Patient and graft survivals are nearly equal to those of ABO-compatible renal transplantation. Despite removal of ABO blood group antibodies before transplantation, hyperacute rejection may occur in some cases. Acute humoral rejection is the most frequent type of early rejection in an ABO-incompatible recipient, but most of these crises are controllable with the most effective antirejection therapy. Further immunopathologic studies are needed to clarify the rejection mechanism in the ABO-incompatible renal transplants. To obtain a successful outcome, immunologic preparation, including reduction of anti-A and anti-B antibody titers and splenectomy, is recommended, along with careful monitoring of antibodies, platelet counts, complement, and kidney function.

Conversion of ABO Blood Groups

Progress is being made toward producing erythrocytes similar to native group O cells from A and B donors. Blood group A and B antigens are known to be carbohydrate in nature. The antigenicity is conferred by different terminal sugars. Removal of these sugars by specific exoglycosidases produces the H antigenic structure that is the determinant found on group O cells. Conditions have been developed that allow for the removal of these antigens while maintaining the metabolic and membrane viability of the red cell. Following successful autologous transfusions with gibbons, appropriately treated human group B erythrocytes are now being used in preclinical studies with normal healthy human volunteers. Results indicate that such treated cells have normal in vivo life spans in both group A and O recipients. However, the latter exhibit a transitory increase in anti-B antibody titer, the significance of which is not yet known. Similar exoglycosidic treatment of group A erythrocytes does not remove all serologically detectable A antigens. This is probably due to the presence of a second internal A antigenic site adjacent to the usual terminal A antigen on some structures. Several approaches are being used to address this problem, including projected treatment with a combination of pertinent exoglycosidases and a search for an endoglycosidase that will cleave the polysaccharide chain at a site upstream from both A antigens.

HLA適合血小板輸血

In seven acute leukemia patients treated with the transfusion of platelets derived from random donors, the mean interval from the beginning of the platelet transfusion to the anti-HLA antibody detection was found to be 2.7 months. HLA-matching platelet transfusions were effective in all of these seven cases, the corrected platelet increment after 24 hours (CPI 24) being 1.27±0.93. In one of them, HLA-matching platelets instead of platelets derived from random donors were necessary, even after the disappearance of his anti-HLA antibody. In this patient of blood type A having received frequent ABO-mismatching platelet transfusions, the CPI 24 of ABO-identical platelet transfusions was compared with that of incompatible transfusion. The CPI 24 of the latter tended to be lower, and furthermore, ABO-incompatible platelet transfusions caused increment of anti-B alloimmunized antibody titer reaching as high as 1: 128,000, thereafter transfusions of AB or B type platelets being ineffective. In such a situation, ABO-identical platelets seemed to be needed.

Immunobiological function of trophoblast to circulating maternal IgG antibodies; antibodies to major transplantation antigens.

IgG anti-A and anti-B were isolated from one patient who showed extremely high anti-A and anti-B antibody titers by the indirect antiglobulin test. These IgG were conjugated with horseradish peroxidase (HRP). A human term placenta of blood type B from a type-O mother was incubated in a solution containing these anti-A and anti-B IgG-HRP conjugates.It is indicated that anti-A and anti-B IgG-HRP are endocytosed into the syncytiotrophoblast but these IgG-HRP lose it's character as immunoglobulin promptly after endocytosis from the results obtained, i.e., positive peroxidase reaction was widely observed inside the trophoblast but immunofluorescence carried out by use of rabbit anti-human IgG/FITC was positive only at the apical portion of the syncytiotrophoblast. On the contrary, in the control experiments used of the same placenta of the experiment and non-specific human IgG-HRP, it is verified that non-specific human IgG was transfered across the syncytiotrophoblast into the fetal side without changing its charactor as immunoglobulin.These results might support our hypothesis published in 1976, under the title of “Immunobiological Function of the Syncytiotrophoblast: A New Theory”, 1 in which we explained how the fetus is prevented from circulating maternal IgG class antibodies aimed at fetal antigens, such as HLA and ABO, etc.