Red Blood Cell Antibodies Research Articles

Prevalence of irregular red cell antibody in healthy blood donors attending a tertiary care hospital in North India.

BACKGROUND:Alloantibodies may be detected in blood donors who have either been transfused previously or female donors with previous obstetric events. These antibodies can occasionally cause severe transfusion reaction, if a large amount of plasma or whole blood is transfused, as in massive transfusions and pediatric patients.AIMS:The present study aims to assess the prevalence of red cell antibodies in healthy blood donors at a tertiary care hospital-based blood bank in India.MATERIALS AND METHODS:A total of 82,153 donor samples were screened for irregular red cell antibodies between January 2012 and December 2015 at the Department of Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi. Antibody screening was performed by solid phase method using Immucor Capture–R ready screen (pooled cells) on fully automated immunohematology analyzer Galileo Neo (Immucor Inc., Norcross, GA, USA). Positive tests were further confirmed using Capture-R ready screen (4 cell panel). Advanced investigations to identify the antibody/ies were performed on confirmed positive samples. Antibody identification was conducted using various cell panels (Immucor Capture-R Ready-ID, Panocell-10, Ficin Treated). An advanced technique such as adsorption and elution was performed as per requirement.RESULTS:Screening with pooled cells and 4 cell panel was positive in 227 donors (0.27%), 150 of these donors had autoantibodies, 1 had autoantibodies with underlying alloantibody anti-Jka (0.001%), and 76 had alloantibodies (0.09%) alone in their plasma. Anti-M was the most common antibody (43 donors) identified, followed by anti-D (21 donors). Anti-N was detected in 4; anti-Jka, anti-C, and anti-E in two donors each followed by anti-P1 and anti-Leb in 1 donor.CONCLUSION:Antibodies against red cells can be present in healthy donors detection of which is important in providing safe blood to the patient. The prevalence of red blood cell antibody in healthy donors in this study was found to be 0.27%, while the prevalence of alloantibodies was 0.09%. The majority of alloantibodies were anti-M (56.57%) and anti-D (27.63%).

The development of D antibodies after D-mismatched kidney transplantation in a setting of reduced immunosuppression.

D antigens are not taken into account in the allocation of solid organs. Female transplant recipients with D antibodies as a consequence of D-mismatched kidney transplantation may develop hemolytic disease of the fetus and newborn in future pregnancies. We examined D antibody development in transplant recipients who received D-mismatched kidney transplantation in absence of D prophylaxis and in a setting of reduced immunosuppression. From 1993 until 2015, a total of 1355 kidney patients received transplantations in our center of whom 156 received a D-mismatched graft. A retrospective analysis was conducted; frozen stored sera obtained from transplant recipients 3 months after transplantation were tested for irregular red blood cell (RBC) antibodies using a three-cell screening and an identification panel. In the case of D antibody positivity, additional testing was performed 1 month before transplantation. In seven of 156 (4.5%) transplant recipients we found irregular RBC antibodies after transplantation, of which five (3.2%) were determined to be D antibodies. We observed only one (0.6%) recipient without D antibodies before transplantation. Although the risk of D antibody development is considerably lower after D-mismatched kidney transplantation than D-mismatched pregnancy, anti-D prophylaxis may still be advisable for female transplant recipients of childbearing age.

The incidence and outcome of clinically significant antibodies detected in Rhesus-D positive pregnant women of the Northern Territory.

Haemolytic disease of the fetus/newborn secondary to clinically significant non-Rhesus-D antibodies has risen in importance since the advent of immunoprophylactic anti-D administration to Rhesus-D negative women. Of interest is the incidence of these antibodies in Rhesus-D positive women, who receive less frequent antenatal alloantibody screening. This is of particular concern if the antibodies arise late in pregnancy and may go undetected. To assess the proportion of Rhesus-D positive pregnant women with late developing clinically significant antibodies for haemolytic disease of the fetus/newborn, and whether these resulted in adverse fetal outcomes. A retrospective analysis over a 12-month period at a tertiary hospital in the Northern Territory. Group and antibody screen results in addition to clinical data regarding pregnancy/newborn were collected. Sixty-four of 2612 women (2.5%) had red blood cell antibodies detected during their pregnancy. Of these, 21 clinically significant antibodies were detected in 19 women (0.7% of initial cohort). The most common antibody detected was anti-c (28.5%). In six of these women (0.23% of initial cohort), the antibodies were late developing. Mild jaundice was noted in three newborns with phototherapy required in one. Although clinically significant antibodies were detected during pregnancy, and in a small proportion of cases as a late developing antibody undetected in the first trimester screening, clinical outcomes for the newborn were mild. As such, the cost of retesting all Rhesus-D positive pregnant women in the third trimester would be considerable and unlikely to result in any meaningful clinical benefit.

Severe neonatal thrombocytopenia due to fetomaternal anti-A alloimmunization: A case report

Severe neonatal thrombocytopenia due to fetomaternal anti-A alloimmunization: A case report

Red blood cell alloimmunization in pregnancy during the years 1996-2015 in Iceland: a nation-wide population study.

Red blood cell (RBC) alloimmunization during pregnancy is still a major problem. Historically, anti-D antibodies are most likely to cause severe hemolysis, but other antibodies are also important. In Iceland, postnatal RhIg prophylaxis was implemented in 1969, universal RBC antibody screening was implemented in 1978, but antenatal RhIg prophylaxis is not yet routine. This nation-wide population study gathered data on alloimmunized pregnancies in Iceland between 1996 and 2015. Blood bank alloimmunization data were linked to Icelandic Medical Birth Registry data. RBC antibodies were classified as either clinically significant or clinically nonsignificant. In total, 912 positive antibody screens from 87,437 births were identified (1.04% prevalence). The most frequent antibodies were anti-M (19.4%), anti-E (19.0%), and anti-D (12.5%). Anti-D prevalence among D-negative mothers was 1.1%. Icelandic Medical Birth Registry data were available for 881 (96.6%) pregnancies. In the clinically significant group (n = 474), anti-E (27%) and anti-D (20%) were most common, whereas anti-M was most frequent (53%) in the clinically nonsignificant group (n = 407). Mothers in the clinically significant group were older, more often multigravidae, had more abortions and stillbirths, and had shorter gestational length. Newborns in the clinically significant group were less healthy, had lower weight and Apgar scores, and required more treatment. Among specificities in the clinically significant group, anti-D antibodies were most strongly associated with severe hemolysis. In this study, the prevalence of alloimmunization was similar to that in previous reports. Of all clinically significant antibodies, anti-D was most strongly associated with severe hemolysis, requiring phototherapy or exchange transfusions. Our data emphasize the importance of implementing an antenatal prophylactic RhIg program in Iceland in the near future.

Red blood cell minor antigen mismatches during chronic transfusion therapy for sickle cell anemia.

Red blood cell (RBC) alloimmunization occurs at a high frequency in sickle cell anemia (SCA) despite serologic matching for Rh (C/c, E/e) and K antigens. RBC minor antigen genotyping allows for prediction of antigens and RH variants that may lead to alloimmunization. RBC antigen genotyping was performed on chronically transfused pediatric SCA patients, using PreciseType human erythrocyte antigen (HEA), RHCE, and RHD BeadChip arrays. All patients received C/c, E/e, and K serologically matched units (Category 1); patients with prior RBC antibodies were also matched for Fya , Jkb , and any antibodies (Category 2). The RBC genotypes of all leukoreduced (LR) units transfused over a 12-month period were determined by the prototype HEA-LR BeadChip assay. There were 2320 RBC units transfused to 90 patients in 1135 transfusion episodes. Thirty-five (38.9%) patients had homozygous or compound heterozygous RH variants. Seven new alloantibodies were detected, with alloantibody incidence of 0.706 in 100 units for Category 2 transfusions and 0.068 in 100 units for Category 1 (p = 0.02). Three patients on Category 2 transfusions formed new anti-Jsa and had a higher rate of exposure to Jsa than those who did not form anti-Jsa (20.4 vs. 8.33 exposures/100 units, p = 0.02). The most frequent mismatches were S (43.9%), Doa (43.9%), Fya (29.2%), M (28.4%), and Jkb (28.1%). Alloimmunization incidence was higher in those with prior RBC antibodies, suggesting that past immunologic responders are at higher risk for future alloimmunization and therefore may benefit from more extensive antigen matching beyond C/c, E/e, K, Fya , and Jkb .

Red blood cell sedimentation of Apheresis Granulocytes.

Sedimentation of Apheresis Granulocyte components removes red blood cells. It is used to increase the blood donor pool when blood group-compatible donors cannot be recruited for a patient because of a major ABO incompatibility or incompatible red blood cell antibodies in the recipient. Because granulocytes have little ABO and few other red blood cell antigens on their membrane, such incompatibility lies mostly with the contaminating red blood cells. Video Clip S1 shows the process of red blood cell sedimentation of an Apheresis Granulocyte component. This video was filmed with a single smart phone attached to a commercial tripod and was edited on a tablet computer with free software by an amateur videographer without prior video experience.

D antibodies in pregnant women in multiethnic Suriname: the observational RheSuN study.

Maternal antibodies against the D antigen are the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). In high-income countries, the risk of D immunization has been reduced by routine antenatal and postpartum administration of RhIG from 13% to less than 0.5%. In less-resourced countries, such as Suriname, red blood cell (RBC) antibody screening during pregnancy and prophylactic RhIG administration are not routine. Accurate data on D immunization risk is not available. In the RheSuN (Rhesus Surinamese Neonates) study, the prevalence and the hemolytic potential of maternal D antibodies were investigated. A multicenter cross-sectional study in four major hospitals in Paramaribo, Suriname, covering 90% of approximately 10,000 births yearly in Suriname. Included were D- pregnant women of various ethnicities seeking routine prenatal care and/or their newborns. D antibodies were detected in 19 of 214 D- pregnancies (8.9%; 95% confidence interval, 5.1%-12.7%), in 2.0% of primigravid and 11.7% of multigravid women. The direct antiglobulin test was positive in 11 of 13 tested D+ newborns. Determination of D antibody titers and antibody-dependent cell mediated cytotoxicity (ADCC) assay revealed three newborns at high risk for HDFN (ADCC > 50%). D immunization risk in Suriname women is comparable to the pre-anti-D prophylaxis era in high-income countries. Recommended is free-of-charge routine RBC antibody screening and prophylactic RhIG administration for women at risk for D antibody formation as part of standard of ante- and postnatal care.

Management of delayed hemolytic transfusion reaction in sickle cell disease: Prevention, diagnosis, treatment

Transfusion remains a key treatment of sickle cell disease complications. However, delayed hemolytic transfusion reaction, the most serious complication of transfusion, may be life-threatening if hyperhemolysis develops. This syndrome is generally underdiagnosed because its biological and clinical features resemble those of vaso-occlusive crisis, and red blood cell antibodies are frequently absent. Further transfusions may aggravate the symptoms, leading to severe multiple organ failure and death. It is therefore essential to prevent, diagnose and treat this syndrome efficiently. Prevention is based principally on the attenuation of allo-immunization through the provision of extended-matched RBCs or the use of rituximab. However, such treatment may be insufficient. Early diagnosis might make it possible to implement specific treatments in some cases, thereby avoiding the need for secondary transfusion. Diagnosis is dependent on the knowledge of the medical staff. Finally, many treatments, including steroids, immunoglobulins, erythropoietin and eculizumab, have been used to improve outcome. Improvements in our knowledge of the specific features of DHTR in SCD should facilitate management of this syndrome.

Estimation of digestible tryptophan:lysine ratios for maximum performance, egg quality and welfare of white-egg-laying hens by fitting the different non-linear models

ABSTRACTA total of 360 Hy-Line W-36 hens at 30 wk of age were assigned to 6 dietary treatments that consisted of 6 different (11, 15, 19, 23, 27 and 31) digestible Trp:Lys ratios. Hens were fed the experimental diets from 30 to 36 wk of age. Productive traits were recorded every wk and egg quality was measured at 36 wk of age. Total IgM, IgG, anti-sheep red blood cell antibody titres, plasma corticosterone, serotonine and glucose concentrations and heterophil to lymphocyte ratio (H:L) were determined at wk 6 of the experiment. Results showed a significant improvement (P < .0001) in egg production, egg mass, feed intake, feed conversion ratio and body weight by increasing the standardized ileal digestible (SID) Trp:Lys ratio from 11 to 19. Relative weights of shell (P < .05) and shell strength (P < .06) were affected by dietary treatments. Hens fed graded levels of SID Trp responded by decreasing the H:L ratio in a linear or curvilinear manner (P < .05). The study reported here indicated that the ideal SID Trp:Lys ratio for laying hens ranged from17.5 to 29 based on the response criteria and regression models.

Haemolysis, pure red cell aplasia and red cell antibody formation associated with major and bidirectional ABO incompatible haematopoietic stem cell transplantation.

Acute and delayed haemolysis, alloimmunisation and pure red cell aplasia (PRCA) are potential complications after ABO incompatible haematopoietic stem cell transplantation (HSCT). The aims of this study were to investigate acute and delayed red blood cell (RBC) antibody-associated complications, including haemolysis, PRCA and alloimmunisation in major and bidirectional ABO incompatible HSCT. We retrospectively examined the transplant courses of 36 recipients of bone marrow or peripheral blood stem cells from ABO incompatible donors and evaluated the current practice of performing plasmapheresis in patients with higher isoagglutinin titres. We investigated the role of ABO incompatibility in haematopoietic recovery, transfusion requirements, alloimmunisation and PRCA. Laboratory signs of acute haemolysis were noted in five (14%) patients, one (3%) of whom had clinically overt haemolysis. Patients with haemolysis had IgM titres ≥1:8 and received >16 mL of RBC in the HSCT. In patients with higher titres, plasmapheresis performed prior to the transplant prevented acute haemolysis. Delayed haemolysis was not recorded in the follow up. Haematopoietic recovery and transfusion requirements did not differ notably between patients with and without haemolysis. De novo RBC antibodies were detected in two (5.5%) patients after HSCT, and PRCA was noted in one (3%) patient. Carried out with adequate graft processing, plasmapheresis and blood component support, haemolysis is not a common complication after HSCT. Our results confirm that the occurrence of haemolysis depends on larger RBC volumes and higher isoagglutinin titres. Despite the reduction of patients' isoagglutinin titres by plasmapheresis, we still noted a critical combination for the development of laboratory signs of haemolysis (IgM titre ≥1:8 and RBC volume >16 mL). De novo immunisation to RBC antigens and PRCA are rare events following ABO incompatible HSCT.

The Impact of Extended Typing On Red Blood Cell Alloimmunization in Transfused Patients.

BACKGROUND:Red blood cell (RBC) alloimmunization is still an actual problem in our transfusion practice. In 2011, in addition to the regular ABO/D blood group typing, phenotyping for Rh (C, c, E, e) and Kell antigens was introduced for blood donors and patients undergoing blood transfusion. Our aim was to evaluate the impact of the extended RBC typing and donor/recipient matching on the incidence of RBC alloimmunization.METHODS:A retrospective comparative study was conducted by reviewing RBC request records for about 36,000 patients transfused with RBC in the period from 2013 to 2015 in comparison to the similar study conducted on 47,000 transfused patients in the period from 2005 to 2008. Pre-transfusion serologic testing data were retrieved for analysis. Blood samples with positive antibody screening and positive cross-match were further subjected to antibody identification. All the tests were performed using column agglutination technique (CAT) with ID-cards and reagents from DiaMed in both studies.RESULTS:Irregular RBC alloantibodies were detected in 116 (0.32%) out of 36,000 transfused patients. Multiple transfusions (15.8 units/patient) were given to 450 patients from which 79 (17.5%) had RBC allontibodies. The incidence of RBC alloimmunisation in the rest of the 35,550 transfused patients from which 37 had RBC alloantibodies was 0.10%. A total of 117 alloantibodies were identified in 96 out of the 116 patients with irregular RBC antibodies. Their specificity was as fallows: anti-E (25.6%), -C (6.0%), -c (8.5%), -e (0.85%), -Cw (5.1%), -K (12.8%), -Fya (10.2%), -Fyb (2.5%), -Jka (7.7%), -Jkb (2.5%), -M (9.4%), -S (1.7%), -s (0.85%), -Lua (1.7%), -Leb (3.4%) and anti-Leb (0.85%). Multiple antibodies were identified in 22 of the transfused patients out of which 15 (68.2%) received multiple transfusions. Anti-E was the most common antibody found in more of the 50% of the multiple antibody cases.CONCLUSIONS:The overall incidence of RBC alloimmunization in transfused patients decreased from 0.51% which was the estimated incidence for the period before the introduction of the extended RBC typing (2005-2008) to 0.32% (2013-2015). This is due to the decreased incidence of RBC alloimmunization in the multiply transfused patients from 33.9% to 17.5% respectively. The current frequency of anti-E (25.6%) and -K (12.8%) antibodies in transfused patients are significantly lower than their previous estimated frequencies of 30.4% and 24.0% respectively, as well as the overall frequency of RBC antibodies to Rh+Kell antigens which decreased from 72.4% to 53.8%. Extended donor-recipient matching for C, c, E, e and Kell antigens has proved a beneficial effect on the incidence of RBC alloimmunization in multiply transfused patients.

Association of HLA‐DRB1 and HLA‐DQB1 with red‐blood‐cell alloimmunization in the Czech population

Alloimmune antibodies against red-blood-cell (RBC) antigens induced in susceptible individuals (responders) by transfusion, pregnancy or transplantation may have serious clinical consequences. The aim of this study was to investigate association of alloimmunization against selected RBC antigens with HLA-Class II. A total of 230 responders (106 monoresponders and 124 multiresponders) were enrolled into the study. HLA-DRB1 and HLA-DQB1 variants were determined by PCR-SSO and their frequencies compared between the patients (patient subgroups) and 375 ethnically and regionally matched controls. Development of multiple RBC antibodies was associated with HLA-DRB1*15 and HLA-DQB1*06 allelic groups in the patients, with the relationship being particularly apparent in those with anti-C+D antibodies. Furthermore, DRB1*13 and DQB1*06 were more frequent in multiresponders with anti-E+c antibodies and DRB1*03 and DQB1*02 in those with anti-E+Cw. For the first time, we confirmed the association of HLA-DRB1*15 with RBC antibody multiresponder status and found HLA-Class II associations for three frequent RBC antibody combinations. Our data support the concept that HLA restriction plays an important role in the response to RBC alloantigens.

Sero-prevalence of RBC alloantibodies among Han and minority patients in Xinjiang

The aim of the study was to examine the sero-prevalence and frequency of red blood cell (RBC) alloantibodies (RAAbs) and to investigate the risk factors for producing RAAbs among the Han and Uyghurs in Xinjiang. The RBC antibody screening test and identification were conducted for 45,163 Han and 70,633 Uyghurs admitted to the First Affiliated Hospital of Xinjiang Medical University from October 2010 to December 2014. RBC alloantibodies against the Rh antigens were the most frequent, including anti-E(21.7% in the Han, 21.6% in Uyghurs) and anti-D(18.5% in the Han, 18.2% in Uyghurs). Notably, the sero-prevalence of anti-K and anti-Fy^a was also high in Xinjiang. Transfusion and pregnancy were risk factors among both the Han and Uyghurs; furthermore, Uyghurs had a higher sero-prevalence of RBC antibodies compared to that of Han because of a higher incidence of these risk factors. We concluded that RBC alloantibodies against the Rh factor showed the highest frequency, and antibodies against Asian-related high-frequency antigens, including Fy^a and low-frequency antigens, such as K were notably high in Xinjiang.

Association of HLA-DRB1 and DQB1 alleles with red blood cell alloimmunization in Chinese

Few systematic investigations have assessed the correlations between red blood cell (RBC) antibodies and human leukocyte antigen (HLA)-DRB1 alleles in the Chinese population. In this case-control study, we investigated whether specific HLA-DRB1 alleles were associated with RBC alloimmunization by calculating the odds ratios for the frequencies of HLA alleles associated with alloimmunization to different RBC antigens. Three hundred and eight patients harboring RBC alloantibodies were analyzed as the case group, and the frequencies of the HLA-DRB1and HLA-DQB1 alleles in control individuals were analyzed by collecting data from the China Marrow Donor Program (including more than 1.6 million healthy people). HLA alleles were genotyped by single specific primer-polymerase chain reaction. The development of anti-C was associated with DRB1*07, DQB1*06, and DQB1*08; anti-C,e was associated with DRB1*07 and DQB1*06; and anti-E and anti-M were associated with DQB1. Other associations were identified between anti-E and DRB1*09 and between anti-Le^a and DRB1*01. Thus, our findings confirmed that HLA-DRB1 and DQB1 restriction played an important role in the generation of RBC alloantibodies in Chinese individuals.

Red cell autoantibodies: Selection of blood for transfusion

Introduction: Transfusion of serological safe blood is an essential requirement in transfusion medicine. Development of anti- red blood cell antibodies remains a major problem. Materials and Methods: A study was conducted on 24237 donors and 25155 patients between August 2013 and July 2016 to determine the prevalence of RBC autoantibodies and management of autoantibody screen positive cases. Results: 19 donors (0.078%) were identified with RBC autoantibodies. 16 of 19 donors showed warm autoantibodies (WAAs), one showed cold autoagglutinin and two showed autoantibodies; type not identified. Ten patients (0.039%) were identified with autoantibodies, of which nine showed warm autoantibodies and one showed cold autoagglutinin. Conclusion: Autoantibodies are mostly formed against the high incidence antigens and therefore react with red cells of random donors' blood, causing difficulty in interpretation of cell typing, compatibility testing, antibody detection and antibody identification. There are wide variations in testing and RBC selection practices in patients with WAAs, further studies are required to evaluate and compare different testing algorithms and transfusion strategies.

Frequency of unexpected red blood cell antibodies in Nanjing

Frequency of unexpected red blood cell antibodies in Nanjing

Incidence of unexpected red blood cell antibodies in the north of China

Incidence of unexpected red blood cell antibodies in the north of China

Hemoglobin Α Clearance Is Associated with RBC Antibodies in Chronically Transfused Children with Sickle Cell Anemia

Hemoglobin Α Clearance Is Associated with RBC Antibodies in Chronically Transfused Children with Sickle Cell Anemia

C3 Modulates RBC Antigen to Negatively Regulate Antibody Response

Background:Red blood cell (RBC) transfusion can result in the development of alloantibodies that can make it difficult to find compatible RBCs for future transfusions and increase the risk of hemolytic transfusion reactions. Despite the consequences of RBC alloimmunization, the factors that regulate this process remain relatively unknown. Recent studies suggest that complement deposition on an antigen surface can significantly enhance the immune response to foreign antigen. As many anti-RBC alloantibodies fix complement and RBCs otherwise lack known adjuvants, early antibody-mediated complement deposition may serve as a key regulator that enhances antibody production. To test this, we employed the KEL RBC model system, which employs RBCs that transgenically express the human KEL antigen specifically on RBCs (KEL RBCs). Using this system, we examined the immunological consequence of KEL RBC exposure following transfusion into C57BL/6 wild-type (WT) or complement component 3 (C3) knockout (KO) recipients.Methods: KEL RBCs were transfused into WT or C3 KO recipients, followed by serum collection on days 3, 5, 7, 14, and 21 post-transfusion. Antibody development in WT or C3 KO recipients was examined by flow crossmatch, where serum was incubated with KEL RBCs followed by antibody detection with fluorescently-tagged secondary anti-IgM and anti-IgG antibodies using flow cytometry. To determine the impact of complement deposition on the level of detectable antigen on the RBC surface, RBCs were labeled with the lipophilic dye, DiI, prior to transfusion and then sampled 1, 2, 3, 5, 7 and 9 days post-transfusion. The level of detectable KEL antigen, complement deposition, KEL RBC survival and antibody bound to the RBC surface was measured by flow cytometry. To examine the effect of complement deposition on the level of KEL protein in the RBC membrane post-transfusion, RBCs stroma was isolated at various time points post transfusion, followed by western blot analysis for the KEL protein.Results: While KEL RBCs induced robust anti-KEL antibody formation and C3 deposition in WT recipients, similar exposure to KEL RBCs in C3 KO recipients actually resulted in an unexpected increase in IgM and IgG anti-KEL antibodies when compared to WT recipients. To determine the consequence of C3 deposition, we examined the potential impact of antibody engagement and complement fixation on KEL antigen levels. Consistent with a potential role for complement in directly impacting KEL antigen availability to the immune system, KEL RBCs transferred into WT recipients experienced a decrease in the level of detectable KEL antigen over time that paralleled the development of anti-KEL antibodies and C3 deposition. In contrast, C3 KO recipients failed to experience the same degree of KEL antigen reduction despite the development of significant anti-KEL antibodies over this same time period. Western blot analysis of RBCs post-transfusion revealed that loss of detectable KEL antigen on the RBC surface paralleled a complete lack of detectable KEL antigen in RBC membranes, indicating that C3 may actually facilitate the removal of KEL from the RBC surface.Conclusion: These results suggest an unexpected role for C3 in negatively regulating antibody responses following RBC transfusion. The impact of C3 on the developing alloantibody response strongly suggests that C3-mediated loss of antigen over time likely reduces antigen availability to the immune system, thereby facilitating the inhibition of antibody production over time. These results not only provide novel insight into potential impact of antigen modulation on the development of an immune response to a RBC alloantigen, but also suggest a completely unexpected role for complement in negatively regulating alloantibody production. In doing so, these results suggest that unique differences in complement activity and overall activation following RBC alloantigen exposure between individuals may represent a previously unrecognized factor that influences alloantibody formation following RBC transfusion. DisclosuresNo relevant conflicts of interest to declare.