Detection and Identification of Red Cell Alloantibodies in Multiply Transfused Thalassemia Major Patients: A Prospective Study

Life long red blood transfusion remains the main treatment for β thalassemia major patients. The development of alloantibodies complicates transfusion therapy in thalassemia patients. Alloimmunization to red cell antigens is one of the most important immunological transfusion reaction and causes delayed type of transfusion reaction. A prospective study was conducted from January 2007 to January 2010. This was a cohorts of 115 patients were selected from regular transfusion group and they were followed for two and half year. They were followed up for the effect of transfusion during study period. There was a decline in patient number from 115 to 96 due to mortality and transfer of patient. A total of 96 multiply transfused thalassemia patients were prospectively included in this study and three consecutive samples collected after every 6 months and investigated for the development of alloantibody to red cell antigens. Tests for antibody screening and identification were performed on preserved sample to investigate prevalence and development of red cell alloimmunization by standardized laboratory techniques by same person at Prathama Blood Centre. A total of 96 patients were included in the study. 63 patients were males and 33 females. A total of five single alloantibodies were formed in five patients out of them four (80 %) belonged to Kell blood group system and one (20 %) from Rh system. It was observed that two (1.92 %) of new thalassemia patients developed red cell alloantibodies during study period. Red cell alloimmunization should be kept in mind in the patients receiving multiple transfusions. In present study, alloimmunization rate was 5.21 %. Mean transfusion duration in these patients was 23.90 days, probably due to presence of alloantibody. RBC alloantibody detection on regular interval and corresponding antigen negative blood transfusion is strongly recommended in transfusion dependent thalassemia patients.     

Prevalence and clinical significances of red cell alloimmunization and red cell bound immunoglobulin G in polytransfused patients with thalassemias

The study was to determine the prevalence and clinical significances of red blood cell (RBC)-bound IgG as detected by flow cytometry in polytransfused patients with thalassemias. Relationship of the presence of RBC-bound IgG with RBC alloimmunization was also evaluated. This study included 59 polytransfused patients with β-thalassemia disease. We studied the frequency of RBC autoantibodies and alloimmunization. Direct Coombs test and flow cytometry were performed to detect the presence of RBC autoantibodies while RBC alloantibodies were detected by antibody screening and identification assays.

Eight (13.6%) and 34 (57.6%) patients were found a positive direct Coombs test and flow cytometry, respectively. Twenty (33.9%) patients developed RBC alloantibodies. The four most frequent RBC alloantibodies were anti-E (55%), anti-Mia (40%), anti-Di(a) (25%) and anti-c (15%), respectively. There was no significant difference in the presence of RBC-bound IgG between polytransfused with thalassemia patients who developed RBC alloimmunization (13 of 20; 65%) and those without RBC alloantibodies (21 of 39; 53.8%), p?=?0.412. Splenectomy and increased transfusion requirement were significantly associated with the presence of RBC-bound IgG but not with RBC alloantibody formation.

The overall frequency of RBC alloantibody formation in polytransfused patients with thalassemias was 33.9%. The most common RBC alloantibody was anti-E. RBC autoantibody formation was more frequently detected by flow cytometry (57.6%) than by direct Coombs test (13.6%). Splenectomy was significantly associated with the development of autoreactive RBC-bound IgG antibodies in the polytransfused patients with thalassemias. The presence of the anti-RBC autoantibodies may cause an increase of transfusion requirement.     

Alloimmunization is associated with older age of transfused red blood cells in sickle cell disease

Red blood cell (RBC) alloimmunization is a significant clinical complication of sickle cell disease (SCD). It can lead to difficulty with cross‐matching for future transfusions and may sometimes trigger life‐threatening delayed hemolytic transfusion reactions. We conducted a retrospective study to explore the association of clinical complications and age of RBC with alloimmunization in patients with SCD followed at a single institution from 2005 to 2012. One hundred and sixty six patients with a total of 488 RBC transfusions were evaluated. Nineteen patients (11%) developed new alloantibodies following blood transfusions during the period of review. The median age of RBC units was 20 days (interquartile range: 14–27 days). RBC antibody formation was significantly associated with the age of RBC units (P = 0.002), with a hazard ratio of 3.5 (95% CI: 1.71–7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66–35.97) for a unit that was 35 days old, 28 days after the blood transfusion. No association was observed between RBC alloimmunization and acute vaso‐occlusive complications. Although increased echocardiography‐derived tricuspid regurgitant jet velocity (TRV) was associated with the presence of RBC alloantibodies (P = 0.02), TRV was not significantly associated with alloimmunization when adjusted for patient age and number of transfused RBC units. Our study suggests that RBC antibody formation is significantly associated with older age of RBCs at the time of transfusion. Prospective studies in patients with SCD are required to confirm this finding. Am. J. Hematol. 90:691–695, 2015. © 2015 Wiley Periodicals, Inc.     

Risk of alloimmunization and delayed hemolytic transfusion reactions in patients with sickle cell disease

Blood transfusion is an integral part of the supportive care of patients with sickle cell diseases. The hazards of red blood cell alloimmunization and delayed hemolytic transfusion reactions (DHTRs) complicate the treatment of patients with sickle cell diseases, particularly since such reactions may be misinterpreted as a pain crisis, and, as a result, specific transfusion serologic studies may not be performed. The frequency of alloimmunization in this population has been the subject of several reports; however, the frequency of DHTRs is unknown. To determine the frequency of this event, we retrospectively reviewed the medical and transfusion service records of all adult patients with sickle cell diseases transfused during the six-year period from January 1980 to December 1985. Seventy-three adult patients with sickle cell diseases received transfusions. The prevalence of recognized DHTR was three (4%) of 73. Red blood cell alloimmunization was seen in 22 (30%) of 73 of the patients. The calculated risk of alloimmunization was 3.1% per unit of blood. These observations suggest that alloimmunization and clinically apparent DHTRs occur more frequently in patients with sickle cell diseases and support pretransfusion testing for at least Rh and Kell red blood cell antigens in patients who are at high risk of such events (patients who have formed an alloantibody or who are being enrolled in a transfusion program).     

Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease

Sickle cell disease (SCD) patients are at increased risk of red blood cell (RBC) alloimmunization. Recipient inflammatory state at time of transfusion has been shown to regulate alloimmunization in murine models, but evidence is lacking in SCD patients. We retrospectively studied a cohort of alloimmunized SCD patients to determine the influence of pro‐inflammatory SCD‐related complications at time of transfusion on alloimmunization. For each transfusion, the presence of pro‐inflammatory state, degree of RBC antigen matching, unit age, storage solution and alloantibody detection date were ascertained. Transfusion‐associated pro‐inflammatory events were compared between transfusions resulting and not resulting in new alloantibodies. Univariate analysis and multivariate logistic regression were performed. Fifty‐two patients received 3166 pre‐storage leuco‐reduced transfusions of which 128 resulted in alloantibodies. Transfusions during inflammatory events were associated with increased alloantibody risk on univariate and multivariate analysis; acute chest syndrome and vaso‐occlusive crisis showed strongest associations with alloimmunization. Increased antigen matching demonstrated a protective effect on alloimmunization (univariate and multivariate analysis). Although an association was seen between citrate‐phosphate‐dextrose (adenine) stored units and alloimmunization on univariate analysis, no effect was found on multivariate analysis. Identifying recipient pro‐inflammatory states at time of transfusion that promote alloimmunization can impact RBC unit selection decisions for SCD patients at risk for alloimmunization.     

Early occurrence of red blood cell alloimmunization in patients with sickle cell disease

Red blood cell (RBC) alloimmunization is a major complication of transfusion therapy in sickle cell disease (SCD). Identification of high‐risk patients is hampered by lack of studies that take the cumulative transfusion exposure into account. In this retrospective cohort study among previously non‐transfused SCD patients in the Netherlands, we aimed to elucidate the association between the cumulative transfusion exposure, first alloimmunization and independent risk factors. A total of 245 patients received 11 952 RBC units. Alloimmunization occurred in 43 patients (18%), half of them formed their first alloantibody before the 8th unit. In patients with exposure to non‐extended matched transfusions (ABO and RhD) the cumulative alloimmunization risk increased up to 35% after 60 transfused units. This was significantly higher compared to a general transfused population (HR 6.6, CI 4.2–10.6). Receiving the first transfusion after the age of 5 was an independent risk factor for alloimmunization (HR 2.3, CI 1.0–5.1). Incidental, episodic transfusions in comparison to chronic scheme transfusions (HR 2.3, CI 0.9–6.0), and exposure to non‐extended matched units in comparison to extended matching (HR 2.0, CI 0.9–4.6) seemed to confer a higher alloimmunization risk. The majority of first alloantibodies are formed after minor transfusion exposure, substantiating suggestions of a responder phenotype in SCD and stressing the need for risk factor identification. In this study, older age at first transfusion, episodic transfusions and non‐extended matched transfusions appeared to be risk factors for alloimmunization. Am. J. Hematol. 91:763–769, 2016. © 2017 Wiley Periodicals, Inc.     

RBC alloimmunization in blood transfusion-dependent beta-thalassemia patients in southern Iran

beta-thalassemia is considered a severe, progressive anemia, which needs regular transfusions for life expectancy. One of the most important complications of regular blood transfusions may be alloimmunization, which increases the need for transfusion. This study was performed to investigate the production of red cell alloantibodies in beta-thalassemia patients in Shiraz, southern Iran. Blood sampling was performed among 711 beta-thalassemia patients in Dastgheib hospital in 2002-2004. Direct and indirect coombs tests were performed to check the auto and alloantibodies and a panel test was conducted to detect the type of alloantibodies. Auto and alloantibodies were observed among 1.7% and 5.3% of patients, respectively. The most common alloantibodies were Anti-kell (50%) > Anti-Rh (D) (15.8%) > Anti-Rh (E) (10.5%). All the patients who had developed alloantibody were in the age group of 6 years or more. So for decreasing the rate of alloantibody synthesis, we should crossmatched the packed cells for minor blood groups especially for kell and Rh(E) in addition to major blood groups from the start of transfusion.     

Alloimmunization and red cell autoimmunization in multitransfused thalassemics of Indian origin

Abstract

Transfusion therapy in thalassemia is a double edged sword, on the one hand, it is a major life saving modality, while on the other hand, it can lead to complications such as alloimmunization. The rates of alloimmunization have been variably reported across the world; however, there is a paucity of such literature among Indian thalassemics. We studied the frequency of alloimmunization and autoimmunization among 211 multitransfused thalassemics of Indian origin. All the patients have been receiving blood matched for ABO and Rh(D) antigens only. Direct antiglobulin test was performed on all patients to detect autoantibody while antibody screening (using 3-cell panel) and antibody identification (11-cell panel) were carried out to detect the presence of alloantibody. The frequency of alloimmunization was 3·79% and that of autoimmunization was 0·47%. The alloantibodies identified were anti-E, anti-K, anti-D, anti-Kp^a, anti-C^w, anti-c and anti-Jk^a. In the present study, no significant association was observed between splenectomy and the development of alloantibodies as well as between age at initiation of transfusion and alloimmunization. To conclude, there is a need to formulate a balanced and cost-effective approach for transfusion management of thalassemics to minimize alloimmunization and autoimmunization.     

Delayed haemolytic transfusion reaction due to anti-M antibody

A female patient with delayed haemolytic transfusion reaction due to anti-M antibody is described. Diagnosis was based on laboratory evidence of haemolysis and on characteristic serological findings. Anti-M was detected in the recipient's serum 7 d after the last transfusion episode. This alloantibody had not been present in the pretransfusion serum. In addition, the direct antiglobulin test was positive on post-transfusion testing and the implicated antibody was eluted from post-transfused red cells.
Delayed haemolytic transfusion reactions have long been recognized as a potencial hazard of transfusion therapy, but such cases due to anti-M are extremely rare.     

Red blood cell transfusions are associated with HLA class I but not H‐Y alloantibodies in children with sickle cell disease

Blood transfusions can induce alloantibodies to antigens on red blood cells (RBCs), white blood cells and platelets, with these alloantibodies affecting transfusion and transplantation. While transfusion‐related alloimmunization against RBC antigens and human leucocyte antigens (HLA) have been studied, transfusion‐related alloimmunization to minor histocompatibility antigens (mHA), such as H‐Y antigens, has not been clinically characterized. We conducted a cross‐sectional study of 114 children with sickle cell disease (SCD) and tested for antibodies to 5 H‐Y antigens and to HLA class I and class II. Few patients had H‐Y antibodies, with no significant differences in the prevalence of any H‐Y antibody observed among transfused females (7%), transfused males (6%) and never transfused females (4%). In contrast, HLA class I, but not HLA class II, antibodies were more prevalent among transfused than never transfused patients (class I: 33% vs. 13%, P = 0·046; class II: 7% vs. 8%, P = 0·67). Among transfused patients, RBC alloantibody history but not amount of transfusion exposure was associated with a high (>25%) HLA class I panel reactive antibody (Odds ratio 6·8, 95% confidence interval 2·1–22·3). These results are consistent with immunological responder and non‐responder phenotypes, wherein a subset of patients with SCD may be at higher risk for transfusion‐related alloimmunization.     

Prevalence,Specificity and Titration of Red Cell Alloantibodies in Multiparous Antenatal Females at a Tertiary Care Centre from North India

Screening and detection of clinically significant antibodies among antenatal women plays an important role in transfusion safety and preventing hemolytic disease of fetus and newborn. Routine screening of antenatal women for antibodies is not done in all blood centres of our country and so immunization rates are not known in pregnant women. We studied the prevalence of alloantibodies and titration of Anti D among antenatal multiparous women in Jammu region. In present prospective study, 750 antenatal multiparous women attending antenatal clinics were typed for ABO and D antigens. Alloantibody screening was done, if positive, specificity of alloantibody was ascertained by using commercially available red cell panel by tube method. Rate of alloimmunization was correlated with Rh D status, gravida, previous transfusion history and bad obstetric history. Titration of alloantibody D was done in first and third trimester of pregnancy. In present study most common blood group detected was B positive (38.4 %). Rh D negative cases constituted 7.6 % of total cases. Rate of alloimmunization was 2 %. A significant correlation was seen between Rh D-negative and alloimmunization (21 % in D-negative and 0.45 % in D-positive). There is significant increasing degree of alloimmunization with increase in Gravida. Alloimmunization in females with bad obstetric history was high (4.41 %) as compared to females with no bad obstetric history showing only 1.76 %. Alloantibodies detected were Anti-D, Anti-E, Anti-C and Anti-K. Anti-D constituted 80 % of all alloantibodies detected. Six women in their third trimester had raised titers of anti-D. Most common alloantibody detected was anti-D (80 %). Alloantibodies to other Rh antigens and Kell blood group systems were also identified. To minimize alloimmunization in Rh D negative women, proper Anti D immunoprophylaxis should be implemented.     

Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and β-thalassemia major

Red blood cell alloimmunization is a major complication of transfusion therapy. Host immune markers that can predict antibody responders remain poorly described. As regulatory T cells (Tregs) play a role in alloimmunization in mouse models, we analyzed the Treg compartment of a cohort of chronically transfused patients with sickle cell disease (SCD, n = 22) and β-thalassemia major (n = 8) with and without alloantibodies. We found reduced Treg activity in alloantibody responders compared with nonresponders as seen in mice. Higher circulating anti-inflammatory IL-10 levels and lower IFN-γ levels were detected in non-alloimmunized SCD patients. Stimulated sorted CD4+ cells from half of the alloimmunized patients had increased frequency of IL-4 expression compared with nonresponders, indicating a skewed T helper (Th) 2 humoral immune response in a subgroup of antibody responders. All patients had increased Th17 responses, suggesting an underlying inflammatory state. Although small, our study indicates an altered immunoregulatory state in alloantibody responders which may help future identification of potential molecular risk factors for alloimmunization.     

Predictors of Red Cell Alloimmunization in Kurdish Multi Transfused Patients with Hemoglobinopathies in Iraq

Abstract

Hemoglobinopathies are significant health problems in Iraq, including its Northern Kurdistan region. One of the essential components of management of these disorders is regular lifelong blood transfusions. The latter is associated with several complications including red cell alloimmunization. No study has looked at the frequency of alloimmunization and its associations in the country. To address the latter issue, 401 multi transfused patients [311 with β-thalassemia (β-thal) syndrome and 90 with sickle cell disease], registered at a large thalassemia care center in Iraqi Kurdistan had their records reviewed, and their sera tested for atypical antibodies using screening and extended red cell panels. Red cell alloimmunization was detected in 18 patients (4.5%) with a total of 20 alloantibodies, while no autoantibodies were detected. The most frequent alloantibody was anti-E, followed by anti-D, anti-K, anti-C^w, anti-C, anti-c and anti-Le^a. Ethnicity was an important predictor of alloimmunization, while age at start of transfusion (>2 vs. ≤2 years) (p?=?0.005), Rhesus D (RhD) negative status (p?=?0.0017) and history of previous transfusion reactions (p?=?0.007) showed a statistically significant higher rate of alloimmunization. However, patients’ age, gender, number of units transfused, underlying diagnosis and splenectomy were not significantly associated with alloimmunization. Based on our observations, measures to reduce alloimmunization rates may include extended matching for Rhesus and Kell antigens and early initiation of blood transfusions.     

Prevalence,specificity and risk of red blood cell alloantibodies among hospitalised Hubei Han Chinese patients

Background

The prevalence, specificity and risk of red blood cell alloantibodies vary widely among different geographic areas, races, and diseases and according to different methods of study, but no data are available on the Chinese Han population, who were investigated in the present study.

Materials and methods

Antibody screening was conducted among 42,517 hospitalised Hubei Han Chinese individuals using column agglutination technology. Samples that were positive in antibody screening were subjected to antibody identification by the tube test. Clinical data, including gender, age, race, transfusion history and records of alloantibody detection, transfusion reactions or haemolytic disease of the newborn, were collected to analyse the prevalence and specificity of alloantibodies and complications associated with them.

Results

A total of 212 patients with alloantibodies were identified among 42,517 patients, yielding a prevalence of 0.50% in this study. Significantly different prevalence rates were observed according to age and sex. The most frequently identified alloantibodies were anti-E (87/212, 41.0%), anti-D (45/212, 21.2%), anti-M (41/212, 19.3%) and a combination of anti-E and anti-c (13/212, 6.1%). Haemolytic disease was observed in 13 infants with anti-D, three infants with anti-E and one infant with anti-Fy^a alloantibodies. Delayed haemolytic transfusion reactions occurred in four patients with alloantibodies.

Discussion

In hospitalised Hubei Han Chinese individuals, the overall prevalence of alloantibodies was 0.50%, with anti-E, anti-D and anti-M being the most frequently identified alloantibodies. These results indicate that anti-D and anti-E alloantibodies were major risk factors for haemolytic disease of the newborn or delayed haemolytic transfusion reactions in this study population.     

RBC alloimmunization and double alloantibodies in thalassemic patients

Abstract

Purpose

Alloimmunization is a common consequence of chronic blood transfusion. Double alloantibody production may complicate the condition of such patients especially for finding matched blood. In this study, we evaluated the frequency of alloantibodies in thalassemic patients with previous history of transfusion reactions.

Samples and methods

This study was performed on 441 multiply transfused thalassemia patients Antibody screening test was carried out using three cell-panel by gel method. Positive patients were followed up for antibody identification using 11-cell panel. Direct combs’ test was performed to detect auto antibodies.

Results

In a total of 441 cases (362 thalassemia major and 79 intermedia), 234 were males (53.1%) and 207 females (46.9%); mean age 22 years, range 3-61 years. Alloimmunization was detected in 50(11.3%) patients, including 37(74%) patients with one alloantibody, 8(16%) with two antibodies, 4(8%) patients with unknown antibodies and one patient (2%) with autoantibody. The most common alloantibodies were anti-Rh antibodies (-E/e/C/c/Cw) (26%), anti-K (28%), anti-D (16%), and anti-Colton (4%). Double antibodies were detected in eight out of 50 patients, including: Anti-D+anti-C (8%), anti-D+anti-E (2%), anti-Kell+anti-D (2%), and anti-Kell+KPa (2%). A significant association was observed between the transfusion reaction history and the alloantibody detection results (p < 0.05).

Conclusion

Antibody production against RBC antigens makes hard condition in regular blood transfusion. Double antibodies production may more complicate this situation. Thus, it is advisable to phenotype patients and matches the red cells in multiply transfused thalassemia patients.     

Low frequency of anti‐D alloimmunization following D+ platelet transfusion: the Anti‐D Alloimmunization after D‐incompatible Platelet Transfusions (ADAPT) study

The reported frequency of D alloimmunization in D? recipients after transfusion of D+ platelets varies. This study was designed to determine the frequency of D alloimmunization, previously reported to be an average of 5 ± 2%. A primary anti‐D immune response was defined as the detection of anti‐D ≥ 28 d following the first D+ platelet transfusion. Data were collected on 485 D? recipients of D+ platelets in 11 centres between 2010 and 2012. Their median age was 60 (range 2–100) years. Diagnoses included: haematological (203/485, 42%), oncological (64/485, 13%) and other diseases (218/485, 45%). Only 7/485 (1·44%; 95% CI 0·58–2·97%) recipients had a primary anti‐D response after a median serological follow‐up of 77 d (range: 28–2111). There were no statistically significant differences between the primary anti‐D formers and the other patients, in terms of gender, age, receipt of immunosuppressive therapy, proportion of patients with haematological/oncological diseases, transfusion of whole blood‐derived or apheresis platelets or both, and total number of transfused platelet products. This is the largest study with the longest follow‐up of D alloimmunization following D+ platelet transfusion. The low frequency of D alloimmunization should be considered when deciding whether to administer Rh Immune Globulin to D? males and D? females without childbearing potential after transfusion of D+ platelets.     

从不规则抗体及抗原分布分析组建稀有血型库的必要性与策略

目的：发现有临床意义的不规则抗体,建立稀有血型库,为患者提供抗原相同的血液,确保输血安全及新生儿溶血病的发生。方法：本分析采用凝聚胺、抗球蛋白、菠萝酶等方法,对随机无偿献血者6000例,医院随机患者4100例做不规则抗体筛选比较,根据抗体的分布组建稀有血型库。结果：检出不规则抗体56例,女性38例高于男性18例（P〈0.01）,产生不规则抗体者多有输血史或妊娠史41例（73.2%）,Rh抗体26（46.4%）为多见,Rh抗原分布特点,E、C、c、e抗原阳性比D抗原阳性低,产生抗体的机率高于抗-D。结论：随机混合O型红细胞容易漏检个别抗体。各供、受血单位应坚持对献血者及受血者进行不规则抗体的筛选和鉴定。规范配血方法,减少输血不良反应的发生。     

Red Cell Alloantibodies in Patients with Thalassemia

We present the results of tests carried out to detect alloimmunization against red cells in 1,200 patients (607 males and 593 females), transfused and followed up during the period 1981-1987 in our hospital. Of these patients, 1,135 were thalassemic and 65 had sickle cell/beta-thalassemia. In 162 patients who received blood matched for the AB0, rhesus and Kell systems from their first transfusion, the immunization rate was very low (3.7%). In a pilot group consisting of 83 patients with the same clinical characteristics, who received blood matched only for the AB0 and Rh-D antigens, there was a significant difference in the frequency of alloantibodies (15.7%, p less than 0.001). Of 1,038 patients who received blood only matched for AB0 and Rh-D 244 (23.5%) with one or more red cell alloantibodies were identified. Of these 1,038 patients, 973 were exclusively thalassemic. In 220 (22.6%) of them, alloantibodies were found. The sickle cell beta-thalassemia patients presented alloantibodies with a higher frequency (36.9%, 24/65). Only one antibody was found in 114 patients (51.8%) and two or more in 106 patients (48.2%). The alloimmunization significantly concerned the rhesus (34.0%) and Kell (29.8%) systems. Anti-Kell was most often identified (28.5%). Alloimmunization appears considerably lower in patients in whom blood transfusion is started before the age of 3 than in those in whom it is started after that age (20.9 vs. 47.5%, p less than 0.0001).     

Issue Information

Most sickle cell disease (SCD) patients rely on blood transfusion as their main treatment strategy. However, frequent blood transfusion poses the risk of alloimmunization. On average, 30% of SCD patients will alloimmunize while other patient groups form antibodies less frequently. Identification of genetic markers may help to predict which patients are at risk to form alloantibodies. The aim of this study was to evaluate whether genetic variations in the Toll-like receptor pathway or in genes previously associated with antibody-mediated conditions are associated with red blood cell (RBC) alloimmunization in a cohort of SCD patients. In this case-control study, cases had a documented history of alloimmunization while controls had received ≥20 RBC units without alloantibody formation. We used a customized single nucleotide polymorphism (SNP) panel to genotype 690 SNPs in 275 (130 controls, 145 cases) patients. Frequencies were compared using multiple logistic regression analysis. In our primary analysis, no SNPs were found to be significantly associated with alloimmunization after correction for multiple testing. However, in a secondary analysis with a less stringent threshold for significance we found 19 moderately associated SNPs. Among others, SNPs in TLR1/TANK and MALT1 were associated with a higher alloimmunization risk, while SNPs in STAM/IFNAR1 and STAT4 conferred a lower alloimmunization risk.