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The role of anti-HLA antibodies in allogeneic stem cell transplantation setting is still unclear. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This article offers the recommendations of the group that considered the impact that have anti-HLA antibodies on outcomes in allogeneic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Purpose of the study Use of matched red blood cell (RBC) concentrates is imperative in patients with RBC allo-antibodies (Abs) and when platelet (PLT) specific allo-Abs are present additional difficulties occur for PLT transfusions. In order to evaluate the prevalence of the PLT and RBC allo-Abs association, a study on patients with PLT specific allo-Acs was performed. This association is not a rare event. Patients and methods In the database of a PLT immunohaematology laboratory, patients with PLT specific allo-Abs were selected and the presence and specificity of RBC allo-Abs was evaluated. Results Six hundred and eighty seven patients (673 females, 14 males) with PLT specific allo-Abs were found. Six hundred and seventy-five patients (98.3%) had PLT specific allo-Abs with only one specificity. Anti-HPA-5b was the most frequent (539 cases). Twenty-nine (4.2%) patients had also RBC allo-Abs, including 27 females (93.1%) and two males. Seventy (58.6%) had RBC allo-Abs with only one specificity, 10 several and two unknown. Among the first, RBC allo-Abs directed against Rhesus blood group antigens were predominant (11 cases [64.7%]). Among the 29 patients with associated PLT and RBC allo-Abs, 15 (51.7%) were 50 or more years old and 14 (48.3%) under 50. Conclusion In PLT specific alloimmunized patients, detection of RBC alloimmunization is not a rare event. When RBC and PLT transfusions are required, the supply of matched RBC and PLT concentrates is more difficult. [ABSTRACT FROM AUTHOR]

Abstract: We report the perioperative management of a woman expressing an antibody against high frequency red cell antigen (anti-Kel4 antibody anti-kpb) who was scheduled for a total knee replacement. A specific strategy was designed to afford this major orthopedic surgery, considering specially the occurrence of unusual bleeding higher than the average bleeding assessed in our hospital in this indication. The transfusion of incompatible red cells may be responsible for acute hemolytic reaction. An autologous transfusion program, including cryopreservation, erythropoietin and iron support, was provided. Three autologous red cells units were collected before surgery. Compatible homologous red cells units were also available at the French bank for rare blood groups. We report logistical and medical problems that have occurred during the perioperative period. [Copyright &y& Elsevier]

Summary: The major histocompatibility complex is a multigenic system highly polymorphic coding for human leukocyte antigen (HLA) molecules, which are the strongest antigens for immune response and play a major role in allograft rejection. Class I antigens are expressed on almost all nucleated cells and platelets, whereas HLA class II antigens are mostly on antigen presenting cells. During transfusion, anti-HLA antibodies can induce transfusion incidents like fever, transfusion-related acute lung injury TRALI and refractoriness to the platelets transfusion. Identification of HLA class I antibodies is very important to find HLA compatible platelets concentrates. Since the end of 1960s, the complement-dependant microlymphocytotoxicity assay has been the standard internationally recognized method for cross matching and screening of HLA antibodies. It became necessary to improve the test sensitivity because some clinical relevant antibodies were not detected. Sensitive methods appeared in the 1990s: flow cytometry, enzyme-linked immunosorbent assay and now Luminex™. This latter is the most sensitive method with single HLA antigen panel assays to generate the most informative reactivity pattern of antibodies. The high sensitivity and specificity of the Luminex™ technology performed to screen HLA antibodies allows the best selection of platelets donors. When no compatible concentrates are available for highly immunized recipients, the cross-matching method could be used to select a platelet concentrate. [Copyright &y& Elsevier]

Abstract: Despite the generalization of immunoprophylaxis by anti-RH immunoglobulins over 40 years, fetomaternal incompatibility due to RH1 antigen (RhD) is not completely eradicated, although perinatal consequences might be extremely serious. Additionally, allo-immunizations against other antigens, especially anti-RH4 (anti-c) and anti-KEL1 (anti-Kell), may cause severe haemolytic disease. Follow-up of allo-immunization during pregnancy and its prevention are therefore still a concern for all pregnant women. Immunohaematological tests used in antenatal patients are under practice for a long time. However, despite significant progress, it is clear that these tests provide only an indirect indication and will only help the obstetrician, in conjunction with over fetal parameters, to assess the severity of the haemolytic disease. Since almost two decades, fetal RHD genotyping became a reality, first using amniocytes, but more recently by analyzing fetal DNA present in the maternal plasma. RH prophylaxis concerns RH:-1 women, who are non-sensitized against RH1 antigen during and at the end of their pregnancy with a RH1 child. RH prophylaxis includes targeted prophylaxis after foetomaternal haemorrhage and now routine antenatal RH prophylaxis at 28 gestation weeks. Indications for RH prophylaxis and immunohaematological testing to assure an efficient therapeutic prevention have been summarized in France through specific recommendations of the National College of Gynecologists and Obstetricians. [Copyright &y& Elsevier]

Abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by a chronic inflammation affecting multiple tissues and the production of antibodies directed against nuclear antigens. Leading observations in patients suggested years ago that interferon-alpha (IFNα) was involved in SLE pathogenesis. These observations have now been confirmed in SLE-prone mice. New promising therapeutic strategies, aiming at neutralizing IFNα or its effects, are currently under development. [Copyright &y& Elsevier]

Abstract: A rare blood group is usually defined as the absence of a high prevalence antigen or the absence of several antigens within a single blood group system, if its prevalence in France is 4/1000 or less in the general population. An individual with a rare blood phenotype can develop a naturally-occurring or immune antibody corresponding to his rare specificity. In case an extremely low stock of compatible blood is available at the national level, a so-called “transfusion deadlock” is described. Most of the individuals with a rare blood group are coincidently identified when a routine pretransfusion testing or pregnancy follow-up is performed, if the antibody(ies) corresponding to the rare specificity is(are) present. Other individuals are discovered following a systematic red cell typing, or family investigations in siblings. One hundred and twenty-one rare blood specificities and 42 rare blood genotypes are currently defined at the French National Reference Laboratory for Blood Groups (CNRGS–Paris). The French national registry of individuals with a rare blood phenotype/genotype includes about 9600 people, who are urged to regularly donate blood for the National Rare Blood Bank. This bank, based on a homologous blood transfusion program, is in charge of the long-term storage of rare frozen blood units, that can only be delivered after receiving authorization from the CNRGS. The global and individual care management of the individuals with a rare blood group, concerning potentially several hundred thousand people in France, requires a close cooperation between all the protagonists within the transfusion chain. [Copyright &y& Elsevier]

Abstract: Antitetanus antibodies titration is carried out by French National Blood Services (FNBSs) with the aim of seeking donors whose title of antibodies are greater or equal to 8IU/ml. Different kits are used: ELISA antitetanus toxoid IgG (The Binding Site), ELISAT (Diagast), tetanus toxoid IgG ELISA (Diamed), ELISA IgG tetanus (Ingen). As the results obtained using these different reagents show some discrepancies with the control results carried out by the Laboratoire Français des Biotechnologies (LFB), it appeared necessary to harmonize the selection practices. With this intention a study of the different kits was initiated. Method: Different samples were used during this evaluation: (1) the Reference Control (RC) used by the FNBS; (2) a serum sample of high title; (3) a range of dilution of national standard. The following tests were carried out: (1) robustness with the evaluation of the contamination and the board effect; (2) linearity and repeatability (eight deposits of each standard, RC and points of national standard dilutions); (3) reproducibility; (4) homogeneity. After automatic dilution of the samples, the plates were then processed according to the protocol of the manufacturer. Results: The study gives the CV in percentage of repeatability and reproducibility, the values of the standards provided as well as the biais compared to the RC and the uncertainty of measurements. Conclusion: This study gave the possibility to rank each kit compared to RC and to specify the variations which surround each result. This variation can explain the discrepancy of conformity of plasma when title is close to the threshold of selection. [Copyright &y& Elsevier]

Abstract: Despite the generalization of immunoprophylaxis by anti-RH immunoglobulins since 1970 and improved management of at-risk pregnancies, allo-immunization due to the RH1 antigen (formerly known as Rhesus D or Rh D) remains widespread. In fact, anti-RH1 antibodies currently constitute over one-third of the immune antibodies detected after pregnancy. At the same time, allo-immunizations against others antigens than anti-RH1, especially anti-RH4 (anti-c) and anti-KEL1 (anti-Kell) increase. Allo-immunization, its follow-up during pregnancy, and its prevention are therefore still topical, and concern all the pregnant women. Immunohematological tests used in antenatal patients have gone a long way. However, despite a great deal of progress, we should not loose sight of the fact that these tests give only an indirect measurement and will only help the obstetrician, in conjunction with other fetal parameters to assess the severity of the haemolytic disease. The best method to assess the severity is the determination of the level of fetal hemoglobin after fetal blood sampling but this procedure is not without risk. Since 13 years, it is possible to determine the fetal RHD genotype of using amniocytes and to day directly with maternal plasma. All pregnant women should be blood-typed for ABO-RH-KEL1 and the blood tested for clinically irregular antibodies. The trend in anti-RH levels is more important than the level itself. Manual titration is simple but only provides rough, semiquantitative estimates of anti-RH concentration. Quantitative hemagglutination methods, using auto-analyzers and appropriate anti-RH1 standards, measured in μg/ml, are sensitive, rapid and have acceptable intra-laboratory reproducibility. RH:-1 women who are non-sensitized against RH1 antigen during and at the end of their pregnancy with a RH1 child. RH prophylaxis includes targeted prophylaxis after feto-maternal hemorrhage and now routine antenatal RH prophylaxis at the 28th week of gestation. It has been necessary to synthesize the indications of RH prophylaxis and immunohematological tests to assure an efficient therapeutic prevention. [Copyright &y& Elsevier]

Abstract: We have analysed the clinical features and autoantibody profile of 84 tunisian patients with newly diagnosed systemic lupus erythematosus (SLE). Antinuclear antibodies (ANA) were detected by an immunofluorescence method, anti-dsDNA and anti-cardiolipin (aCL) antibodies by ELISA, antinucleosome and anti-extractible nuclear antigens (or anti-ENA : anti-Sm, anti-RNP, anti-SSA and anti-SSB) by immunodot. The mean age of the patients was 29,9 years and the sex-ratio F/M was 6. The most common initial features were haematological (80%), rheumatological (78%) and cutaneous (75%) disorders. 59% of the patients had glomerular nephropathy. ANA were detected in 97,6%, antinucleosome in 78,6%, anti-dsDNA in 75%, anti-histones in 44%, anti-Sm in 36,9%, anti-RNP in 32,1%, anti-SSA in 54,8% and anti-SSB in 14,3% of patients. IgG and IgM aCL were detected in 45 and 40% of the patients respectively. The significant clinical associations were those of nephropathy and disease activity with anti-dsDNA and antinucleosome antibodies. Our results confirm the clinical polymorphism of SLE, the high frequency of antinucleosome antibodies at time of diagnosis and the predominance of anti-SSA among anti-ENA antibodies. [Copyright &y& Elsevier]

Purpose. – Auto-immunity against Ku nuclear antigens is rare and clinical meaning remains badly estimated. Our study is for purposes: to appreciate the prévalence of antibodies anti-Ku within the framework of the search for antinuclear antibodies and to clarify clinical and biological relations associated to this auto-immunity.Methods. – A retrospective study of a series of 10 000 searches for antinuclear antibodies studies the prévalence of the auto-immunity anti-Ku and a retrospective analysis of the data found at the patients bearers of an anti-Ku identifies clinical and biological signs associated with this antibody.Results. – Prévalence anti-Ku is low (1/3493 case of antinuclear antibodies) and association is possible with in a myositic process through variable auto-immune contexts (overlap syndrome) of relative good preview.Conclusion. – Auto-immunity anti-Ku is so characterized with its weak prévalence, a possible observation during different auto-immune diseases with an obvious frequency of the overlap syndrome often concerning a process myositic. Finally a weak évolutivité seems to characterize the auto-immune diseases of the patients with anti-Ku antibodies. [Copyright &y& Elsevier]

Alloimmune thrombocytopenia is due to feto-maternal incompatibility in the HPA systems and is usually considered in the diagnosis of neonatal thrombocytopenia after other causes have been excluded. We report on two Tunisian observations of alloimmune neonatal thrombocytopenia due to anti-HPA-5b (Bra) antibodies.Case report. – Two neonates presented at birth with a thrombocytopenic purpura unexplained by usual causes of neonatal thrombocytopenia. Alloimmune neonatal thrombocytopenia was diagnosed by the determination of parental and neonatal platelets antigens phenotypes and by the presence of HPA-5b (antiBra) antibodies in maternal sera. A favourable evolution was obtained after maternal platelet transfusions.Conclusion. – Alloimmune neonatal thrombocytopenia is a serious affection, which exposes to intracranial haemorrhage. These observations of HPA-5 neonatal alloimmunisation in Tunisia provide additional information on the geographic distribution of the disease and its prognosis. [Copyright &y& Elsevier]

Polymorphism encountered within the immunogenic blood group antigens is responsible for allo-immunization after transfusion or pregnancy. Antigen frequency differs depending on the ethnic background. This is the case for the Afro-caribbean population. Three levels of differences can be identified: common antigens in the RH, FY, JK and MNS blood groups, high frequency antigens in the RH, KEL, FY and MNS blood groups and low frequency antigens in the RH and KEL blood groups. When donors are primarily European caucasian in ancestry, the ethnic polymorphism may affect donor service in term of supply and demand. The effects of differences in antigen frequency are especially important when long term transfusion support is needed such as in sickle cell disease. When a Black patient is immunized against an association of common antigens for the Caucasian population (ex: anti-RH2, anti-FY1, anti-JK2, anti-MNS3) or against a high frequency antigen always present in the Caucasian population (anti-MNS5), only rare blood from the same ethnic population kept frozen at the rare blood bank can be transfused to avoid immuno-haemolytic accidents. [Copyright &y& Elsevier]

Abstract: Fetal and neonatal alloimmune thrombocytopenia due to mothers'' anti-HPA-5b alloimmunization has generally a milder clinical presentation compared to anti-HPA-1a alloimmunization. Nevertheless, a case with infant''s death probably due to intracranial haemorrhage has been reported. However, if platelet-specific alloimmunized mothers with prior fetal or neonate injury receive intravenous immunoglobulins during pregnancy, thrombocytopenia in heterozygous fetus and neonate may be prevented. Here are reported 2 cases of anti-HPA-5b fetal-maternal alloimmunization, one with prior fetal death, the other with prior severe fetal intracranial haemorrhage, which were successfully treated with intraveinous immunoglobulins alone during a second pregnancy with HPA-5b incompatibility. [Copyright &y& Elsevier]