Red-blood-cell alloimmunization and number of red-blood-cell transfusions

Background Patients receiving red‐blood‐cells may form antibodies against the alloantigens expressed by red‐blood‐cells, with the risk of serious morbidity and the need for extensive phenotype‐matching in subsequent transfusions. The incidence of alloimmunization is considered variable for specific patient groups and for first time antibody formation. We therefore studied the cumulative incidence of the first formed alloantibody as a function of red‐blood‐cells exposure. Methods We performed a new‐user cohort among all previously non‐transfused non‐alloimmunized patients that received non‐extended matched (ABO and RhD) red‐blood‐cells transfusions from January 2005 to December 2009 in our university medical centre. Alloimmunization incidences were estimated by Kaplan–Meier survival‐analysis. Results A total of 3002 previously non‐transfused patients received 31 103 red‐blood‐cell units. A first time alloantibody forming event was experienced by 54 (1·8%) patients. The cumulative incidence of alloimmunization was 1·0% at 5 units, 2·4% at 10 units, 3·4% at 20 units and 6·5% at 40 units of red‐blood‐cells transfused. Conclusion The risk to develop a first red‐blood‐cells alloantibody increases up to the 40th transfusion and is similar for men and women. More data are needed to examine the risk after 40th transfusion.     

Red cell alloimmunisation in patients with different types of infections

Red cell alloantigen exposure can cause alloantibody‐associated morbidity. Murine models have suggested that inflammation modulates red cell alloimmunisation. This study quantifies alloimmunisation risks during infectious episodes in humans. We performed a multicentre case–control study within a source population of patients receiving their first and subsequent red cell transfusions during an 8‐year follow‐up period. Patients developing a first transfusion‐induced red cell alloantibody (N = 505) were each compared with two similarly exposed, but non‐alloimmunised controls (N = 1010) during a 5‐week ‘alloimmunisation risk period’ using multivariate logistic regression analysis. Transfusions during ‘severe’ bacterial (tissue‐invasive) infections were associated with increased risks of alloantibody development [adjusted relative risk (RR) 1·34, 95% confidence interval (95% CI) 0·97–1·85], especially when these infections were accompanied with long‐standing fever (RR 3·06, 95% CI 1·57–5·96). Disseminated viral disorders demonstrated a trend towards increased risks (RR 2·41, 95% CI 0·89–6·53), in apparent contrast to a possible protection associated with Gram‐negative bacteraemia (RR 0·58, 95% CI 0·13–1·14). ‘Simple’ bacterial infections, Gram‐positive bacteraemia, fungal infections, maximum C‐reactive protein values and leucocytosis were not associated with red cell alloimmunisation. These findings are consistent with murine models. Confirmatory research is needed before patients likely to develop alloantibodies may be identified based on their infectious conditions at time of transfusion.     

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.     

Reducing the incidence of TRALI in the UK: the results of screening for donor leucocyte antibodies and the development of national guidelines

Background and Objectives Transfusion‐related acute lung injury (TRALI) is associated with the passive transfusion of leucocyte antibodies in blood products. Blood Transfusion Services have adopted a number of different strategies for reducing the incidence of TRALI, but, while these have been successful, TRALI has not been completely eliminated. Many Transfusion Services have introduced leucocyte antibody screening of donors to further reduce TRALI. This report describes the results of donor leucocyte antibody screening within NHS Blood and Transplant and the guidelines that have been developed for Transfusion Services within the United Kingdom (UK) to reduce the incidence of TRALI. Materials and Methods Blood samples from newly recruited female apheresis donors were tested for human leucocyte antigens (HLA) class I and class II antibodies and granulocyte‐specific antibodies. Results A total of 1157 female donors were evaluated. Three hundred and fifteen (27·23%) donors had HLA class I or II antibodies and were returned to red cell component donation. Fifty‐seven (6·77%) of the remaining 842 donors were found to have granulocyte‐specific antibodies of which 11 (1·31%) had HNA‐specific antibodies. A total of 818 donors (70·70%) were accepted for platelet apheresis, 336 donors (29·04%) were returned to red cell component donation, and three donors with HNA‐3a antibodies (0·26%) were deferred from therapeutic donation. Conclusions Female donors with leucocyte antibodies were identified in a stratified screening programme. Donors with antibodies were either directed to red cell donation or deferred. This process, combined with other measures that have already been introduced, is anticipated to further reduce the incidence of TRALI.     

Prevalence of leucocyte antibodies in the Dutch donor population

Introduction Donor leucocyte antibodies have been associated with transfusion‐related acute lung injury (TRALI) and can be present in allo‐exposed donors. Donor deferral policies aiming at excluding allo‐exposed donors are increasingly implemented worldwide. We aimed at assessing the prevalence of leucocyte antibodies in different subgroups of allo‐exposed donors in the Dutch donor population. Methods Consecutive donors were enrolled during routine whole blood donation. Donors filled out a questionnaire on allo‐exposure history. Blood samples were tested for human leucocyte antigens (HLA) (LifeScreen Deluxe and the Lifecodes LSA I/II assays) and granulocyte‐reactive (GIFT, GAT, and MAIGA) antibodies. Results Six thousand and thirty‐four consecutive donors (60% men) were included. A total of 2·5% reported a history of blood transfusions, and 51% (of female donors) reported a history of pregnancy. In never allo‐exposed donors, the prevalence of granulocyte‐reactive antibodies was 2·0% (95% CI: 1·6–2·4), and for HLA antibodies, it was 7·0% (95% CI: 6·3–7·8). In previously pregnant donors, the prevalence of granulocyte‐reactive antibodies was increased to 3·0% (95% CI: 2·0–4·0), and for HLA antibodies, it was increased to 33% (95% CI: 30–36). Prevalence of leucocyte antibodies of all types depended on transfusion history, number of pregnancies, time since last pregnancy, and pregnancy outcome. Conclusions Fourteen percent of Dutch blood donors are allo‐immunized against HLA or granulocyte antigens. Deferral of all self‐reported allo‐exposed donors will decrease this prevalence to 9%. Deferral of all female donors and transfused male donors will result in a similar prevalence among remaining donors but approximately twice as many deferrals.     

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.     

Factors associated with persistence of red blood cell antibodies in woman after pregnancies complicated by fetal alloimmune haemolytic disease treated with intrauterine transfusions

Red blood cell (RBC) antibodies can persist for decades or decrease quickly to undetectable levels. Antibody persistence has not been systematically studied. Women whose children are treated with intrauterine transfusions (IUT) for haemolytic disease of the fetus (HDFN) often produce additional antibodies, which can be evoked by the intrauterine transfusion or by fetomaternal haemorrhage during the procedure. Factors associated with persistence of both the antibodies responsible for HDFN and additional antibodies were studied in 260 women whose children were treated with IUT between 1988 and 2008. They possessed 499 (205 anti‐D and 294 non‐D) antibodies after the last IUT. After a median follow‐up of 8·7 years, all 260 antibodies primarily responsible for HDFN had persisted. Additional antibodies directed against antigens of the children persisted in 70·6%, and in 32·3% if they were not child‐specific (P < 0·001). Antibodies induced by irradiated IUT persisted in only 7·1%. Multivariate analyses showed that non‐HDFN antibody persistence was dependent on the antibody titre and specificity. In conclusion, persistence of antibodies mainly depends on antibody strength and specificity. Difference between fetal or non‐fetal immunogens suggests maintenance of antigenic stimulation possibly by long‐term fetomaternal chimerism.     

Prevalence and specificities of red blood cell alloantibodies in transfused Ugandans with different diseases

Background and Objectives Alloantibody formation against red blood cell (RBC) antigens is a common complication of transfusion therapy. However, the prevalence of RBC alloimmunization is hardly known in Black Africans. In Uganda, the practice is to transfuse ABO/D compatible blood without screening for immune antibodies. The aim of this study was to determine the prevalence and specificities of RBC alloantibodies in transfused Ugandans. Materials and Methods Using a cross‐sectional design, transfused patients at Mulago Hospital in Kampala, Uganda were investigated. Demographic characteristics and transfusion histories were recorded. EDTA blood samples were obtained from consenting patients and RBC alloimmunization was demonstrated using immunohaematological tests. Results A total of 214 transfused patients (mean age, 30·3 years; F/M ratio, 1·0) were investigated. Thirteen patients (6·1%) possessed RBC alloantibodies whose specificities were six anti‐E; three anti‐S; one each of anti‐D, ‐K and ‐Le^a; and two samples were pan‐reactive. Eleven (84·6%) of the alloimmunized patients had experienced up to 10 transfusion episodes. The number of units of blood transfused and the transfusion episodes were significantly associated with the RBC alloimmunization rate (P = 0·01). Conclusions The prevalence of RBC alloimmunization in transfused Ugandans was 6·1% and was associated with the number of donor exposures. This immunization rate is similar to that observed in transfused Caucasians despite differences in RBC antigen distributions. Patients with malaria were less likely to develop RBC alloantibodies. Alloantibodies were mainly against E and S antigens. We recommend the introduction of pretransfusion antibody tests in Uganda depending on the recipient’s diagnosis.     

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.     

A cautious iodization programme bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population

Autoantibodies against the thyroid gland with thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (Tg‐Ab) as the most common can often be demonstrated in serum. The effect of public iodization programmes on antibody prevalence is uncertain. Aim To measure the concentrations of thyroid autoantibodies in the Danish population before and after mandatory iodization of salt. Methods Two identical cross‐sectional population studies were performed before (Cohort 1 (C1), year 1997–1998, n = 4649, median urinary iodine 61 μg/l) and 4–5 years after (Cohort 2 (C2), year 2004–2005, n = 3570, median urinary iodine 101 μg/l) mandatory iodine fortification of salt was implemented in Denmark. Blood tests were analysed for TPO‐Ab and Tg‐Ab using sensitive assays. Results Antibodies were more frequent in C2 than in C1: TPO‐Ab > 30 U/ml, C1 vs C2: 14·3 vs 23·8% (P < 0·001) and Tg‐Ab > 20 U/ml, C1 vs C2: 13·7 vs 19·9% (P < 0·001). The C2 vs C1 effect was confirmed in multivariate regression models (C1 reference): TPO‐Ab: OR (95% CI): 1·80 (1·59–2·04) and Tg‐Ab: 1·49 (1·31–1·69). The increase in the frequency of thyroid antibodies was most pronounced in young women and especially observed at low concentrations of antibodies. Conclusion The prevalence of both TPO‐Ab and Tg‐Ab was higher 4–5 years after a cautious iodine fortification of salt was introduced in Denmark. The increase was most pronounced in young women and in the low concentrations of antibody. Further studies are needed to evaluate the long‐term effects of increased iodine intake on thyroid autoimmunity in the population.     

Incidence of Red Cell Alloantibody among the Transfusion Recipients of Universiti Kebangsaan Malaysia Medical Centre

Red blood cell alloimmunization is a common complication among the transfusion recipients. In Malaysia, multiple ethnicity causes genetic heterogeneity among the population which in turn can cause a wide variation of antibody. The objective of this study was to analyse the red cell alloantibody detected during the pre-transfusion testing. This was a cross-sectional study done in the blood bank of Universiti Kebangsaan Malaysia Medical Centre during the period of January–December 2010. The data was retrieved from the hospital laboratory information system. A total of 24,263 patients’ blood samples were subjected for pre-transfusion testing. Antibody screening was done using an indirect antiglobulin test method. The positive samples were further identified for antibody specificity. Antibody screening tests were positive in 184 patients out of 24,263 samples with the incidence of 0.76 %. Autoantibodies and alloantibodies were detected in 39/184 (21.2 %) and 140/184 (76.1 %) of the patients respectively. In five patients (2.7 %) the antibody specificity remained undetermined. Total 161 alloantibodies were identified. The suspected Anti-Mia alloantibody was observed most frequently (49/161, 30.4 %) followed by anti-E (30/161, 18.6 %) and anti-D (22/161, 13.7 %). Anti-E and anti-c were the most common combination of multiple alloantibodies. In view of the high incidence of suspected Anti-Mia antibodies, more efforts are needed to look into the techniques for confirmation of the Anti-Mia antibodies. Besides that, we suggested that all multiply transfused patients should be phenotyped for the Rh system and to supply Rh phenotype specific blood in order to limit alloimmunization.     

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.     

Risk factors for red blood cell alloimmunization in the Recipient Epidemiology and Donor Evaluation Study (REDS‐III) database

Despite the significance of red blood cell (RBC) alloimmunization, the lack of standardized registries in the US has prevented the completion of large studies. Data from 3·5 years of the Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III) recipient database, containing information from 12 hospitals, were studied. A RBC alloantibody responder had an antibody identified at any point during the study, and a non‐responder had a negative antibody screen at least 15 days post‐RBC transfusion. Demographics, blood type, ICD9/10 codes, and other potential correlates were evaluated. Of 319 177 (2·07%) screened patients, 6597 had a total of 8892 clinically significant RBC alloantibodies identified, with 75% being in the Rh or Kell families. Alloimmunization was more common in females (2·38%) than males (1·68%), and in RhD negative (2·82%) than RhD positive (1·94%) patients. Age, sex, RhD status and race were associated with being a responder, and certain diagnoses (including sickle cell disease or trait, systemic lupus erythematosus, rheumatoid arthritis and myelodysplastic syndrome) were more common among responders than non‐responders. Data collected in this multi‐centre recipient database provide the largest RBC alloimmunized patient cohort studied in the US, with previously known demographic and disease associations of responder status confirmed, and new associations identified.     

Human erythroid progenitor cells express Rhesus antigens

The expression of Rhesus antigens on hematopoietic progenitor cells was studied using monoclonal antibodies. Because these antibodies are not capable of lysing mature red blood cells in a complement-dependent cytotoxicity assay, fluorescence-activated cell sorting was performed. Using the monoclonal anti-Rh 29 antibody B10, 68% +/- 6% of the mature erythroid progenitor cells (CFU-E) were sorted into the positive fraction, while only 2% +/- 1% of the relatively immature erythroid progenitor cells (BFU-E), and 3% +/- 1% of the granulocyte-macrophage progenitor cells (CFU-GM) were cultured from this same fraction. Thus up to a 15-fold enrichment of CFU-E could be obtained. In two experiments more than 4% of the cells in the positive fraction consisted of CFU-E; in one experiment even more than 7% did. Using fractionated cell sorting, the Rhesus antigens appeared to have a lower density on CFU-E than HLA-DR determinants. Antibodies against the Rhesus antigens can be applied to enrich erythroid-committed stem cells and to separate mature from immature erythroid progenitor cells.     

Glycosylation pattern of anti‐platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia

Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life‐threatening disease where fetal platelets are destroyed by maternal anti‐platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. We recently found IgG Fc‐glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core‐fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. Here we analysed the N‐linked glycans of human platelet antigen (HPA)‐1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). Besides a significant decrease in Fc‐fucosylation after the first pregnancy (P = 0·0124), Fc‐glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. Multiple logistic regression analysis identified anti‐HPA‐1a –fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity , making these parameters a feasible marker in screening for severe cases of FNAIT.     

Granulocyte‐reactive antibodies are associated with red blood cell alloimmunization

Granulocyte‐reactive antibodies may cause transfusion‐related acute lung injury (TRALI) and immune neutropenias. Risk factors for their acquisition other than previous alloexposition are largely unknown. In addition to the known association between human leucocyte antigen alloantibodies and red blood cell alloimmunization in selected cohorts of transfused patients, this study investigated a possible extension of this association to granulocyte‐reactive antibodies in women with a history of pregnancy. The overall prevalence of granulocyte‐reactive antibodies in 333 samples from women with a history of pregnancy (143 samples containing red cell alloantibodies) was 23·1%. The prevalence in the red cell‐alloimmunized group (32·9%) was significantly higher than in controls (15·8%, P < 0·001). This could suggest that some individuals may be strong immunological responders, forming alloantibodies more readily than others.     

Prevalence of antiphospholipid antibodies in psychiatric patients users and non‐users of antipsychotics

Past reports have suggested that antiphospholipid (aPL) antibodies may emerge as a response to antipsychotics treatment, as a high prevalence of aPL antibodies in antipsychotics users has been observed. However, no control group of non‐medicated psychiatric patients was included in these reports. In a cross sectional study we determined the prevalence of aPL antibodies in 333 psychiatric inpatients. We compared the proportions of positive aPL antibodytests between users and non‐users of antipsychotics with adjustments for potential confounders. The proportion of antipsychotics users carrying at least one aPL antibody ranged from 10·8% to 27·0% compared with 6·8% to 27·2% in non‐users (P = 0·24, P = 0·24) depending on the method of detection of lupus anticoagulant (LA). The prevalence of LA detected by dilute Russell viper venom time or partial thromboplastin time‐LA was not different between antipsychotics users and non‐users (8·1% vs. 5·4%, P = 0·53 and 18·4% vs. 18·2%, P = 0·22), as well as the prevalence of IgM and IgG anti‐β2‐glycoprotein‐I antibodies, IgM and IgG anti‐cardiolipin antibodies(3·8% vs. 2·0%, P = 0·75, 0·0% vs. 0·0%, P = not applicable, 1·1 vs. 1·4%, P = 0·91, 2·7% vs. 3·4%, P = 0·71). In conclusion, aPL antibodies were frequently found in patients with psychiatric diseases and no significant increase in the prevalence of aPL antibodies was observed in antipsychotics users.     

Antibody responses to surface antigens of Plasmodium falciparum gametocyte‐infected erythrocytes and their relation to gametocytaemia

An essential element for continuing transmission of Plasmodium falciparum is the availability of mature gametocytes in human peripheral circulation for uptake by mosquitoes. Natural immune responses to circulating gametocytes may play a role in reducing transmission from humans to mosquitoes. Here, antibody recognition of the surface of mature intra‐erythrocytic gametocytes produced either by a laboratory‐adapted parasite, 3D7, or by a recent clinical isolate of Kenyan origin (HL1204), was evaluated longitudinally in a cohort of Ghanaian school children by flow cytometry. This showed that a proportion of children exhibited antibody responses that recognized gametocyte surface antigens on one or both parasite lines. A subset of the children maintained detectable anti‐gametocyte surface antigen (GSA) antibody levels during the 5 week study period. There was indicative evidence that children with anti‐GSA antibodies present at enrolment were less likely to have patent gametocytaemia at subsequent visits (odds ratio = 0·29, 95% CI 0·06–1·05; P = 0·034). Our data support the existence of antigens on the surface of gametocyte‐infected erythrocytes, but further studies are needed to confirm whether antibodies against them reduce gametocyte carriage. The identification of GSA would allow their evaluation as potential anti‐gametocyte vaccine candidates and/or biomarkers for gametocyte carriage.     

The mean fluorescence intensities of anti‐HLA antibodies detected using micro‐bead flow cytometry predict the risk of platelet transfusion refractoriness

There are no accepted methods to predict the development of platelet transfusion refractoriness (PTR) due to human leucocyte antigen (HLA)‐alloimmunization. Hence, matched platelets are usually given only to patients demonstrating PTR, necessarily resulting in some ineffective random donor platelets (RDPLT) transfusions. To assess its utility in predicting PTR, we retrospectively tested samples from 387 patients receiving chemotherapy for acute leukaemia or autologous transplantation using a micro‐bead flow cytometry assay. The average of the mean fluorescence intensities (avgMFI) of the class I beads in the screening assay was correlated with outcomes of RDPLT transfusions during a 2 week period. Antibodies were detected in 57 patients; 66 developed PTR, of whom 28 were alloimmunized. avgMFI usefully predicted the development of PTR (area under the receiver operating curve 0·87, 95% confidence interval: 0·77–0·96). A logistic regression model estimated the probability of PTR to be >90% when avgMFI >5440. These results indicate that micro‐bead flow cytometry assays could inform a risk‐adapted strategy for managing thrombocytopaenic HLA allo‐immunized patients.