Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn.

Background: In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels.

Methods: In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN.

The c.1291A Allele Leads to a Loss of Membrane Expression and Mimics a CD177-Null Phenotype.

CD177 is a glycosyl phosphatidyl inositol (GPI)-linked, neutrophil-specific glycoprotein that in 3-5% of normal individuals is absent from all neutrophils. The molecular mechanism behind the absence of CD177 has not been unravelled completely. Here, we analyse the impact of the recently described c.

analysis of anti-HPA-1a dependent platelet phagocytosis and its inhibition using a new whole blood phagocytosis assay (WHOPPA).

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a serious bleeding condition mostly caused by the reaction between maternal anti-HPA-1a antibodies and fetal platelets. This reaction leads to Fc-dependent platelet phagocytosis. Although several serological methods have been developed to identify maternal antibodies, a reliable laboratory parameter as a prognostic tool for FNAIT severity is still lacking.

Type 2 T-Cell Responses against Distinct Epitopes of the Desmoglein 3 Ectodomain in Pemphigus Vulgaris.

Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies that predominantly target two transmembrane desmosomal cadherins: desmoglein (DSG)1 and DSG3. DSG-specific T cells play a central role in PV pathogenesis because they provide help to autoreactive B cells for autoantibody production. In this study, we characterized DSG3-specific peripheral T cells in a cohort of 52 patients with PV and 41 healthy controls with regard to cytokine profile and epitope specificity.

Pregnant Women at Low Risk of Having a Child with Fetal and Neonatal Alloimmune Thrombocytopenia Do Not Require Treatment with Intravenous Immunoglobulin.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition in which maternal alloantibodies to fetal platelets cause fetal thrombocytopenia that may lead to intracranial hemorrhage (ICH). Off-label intravenous immunoglobulin (IVIg) has for 30 years been the standard of care for pregnant women who previously have had a child with FNAIT. The efficacy of this treatment has never been tested in a placebo-controlled clinical trial.

Fetal and neonatal alloimmune thrombocytopenia: No evidence of systemic inflammation as a modulator of disease severity. Could placental inflammation be key?

In fetal/neonatal alloimmune thrombocytopenia (FNAIT), maternal alloantibodies against paternal human platelet antigens (HPA) cross the placenta and lead to platelet destruction. The extent of thrombocytopenia varies among neonates, and inflammation may constitute an important trigger. A set of stable inflammatory markers was measured in serum samples from neonates with low platelet counts, of which n = 50 were diagnosed with FNAIT due to anti-HPA-1a antibodies and n = 50 were thrombocytopenic without detectable maternal HPA antibodies.

ABO Incompatibility between the Mother and Fetus Does Not Protect against Anti-Human Platelet Antigen-1a Immunization by Pregnancy.

(1) Background: ABO blood group incompatibility between the mother and fetus protects against anti-D immunization by pregnancy. The possible role of ABO incompatibility in protecting against anti-human platelet antigen-1a immunization is unclear. (2) Methods: This study retrospectively screened 817 families (mother-father-neonate trios) of suspected fetal and neonatal alloimmune thrombocytopenia for inclusion.

Correction: Sommer et al. Decreased Thymic Output Contributes to Immune Defects in Septic Patients. 2020, , 2695.

In the original article, there were errors in Figure 1D (panel CD8-Control) [...

Anti-human platelet antigen-5b antibodies and fetal and neonatal alloimmune thrombocytopenia; incidental association or cause and effect?

Most cases of fetal and neonatal thrombocytopenia (FNAIT) are caused by maternal anti-human platelet antigen-1a antibodies (anti-HPA-1a). Anti-HPA-5b antibodies are the second most common antibodies in suspected FNAIT cases. Given the high prevalence of anti-HPA-5b antibodies in pregnant women delivering healthy newborns, the association with FNAIT may be coincidental.

Transfusion of target antigens to preimmunized recipients: a new mechanism in transfusion-related acute lung injury.

Transfusion-related lung injury (TRALI) is a serious side effect of blood transfusion. Exclusion of antibody carriers from the donor pool has significantly decreased the number of cases, but TRALI remains the leading cause of transfusion-related morbidity and mortality in industrialized countries. Here, we show that proteins released from donor cells during processing of blood components are capable of inducing a new type of reverse TRALI when transfused to preimmunized recipients.

Sex-specific differences in plasma levels of FXII, HK, and FXIIa-C1-esterase inhibitor complexes in community-acquired pneumonia.

Sex-dependent differences in immunity and coagulation play an active role in the outcome of community-acquired pneumonia (CAP). Contact phase proteins act at the crossroads between inflammation and coagulation thus representing a point of convergence in host defense against infection. Here, we measured the levels of factor XII (FXII), FXIIa-C1 esterase inhibitor (C1INH) complexes, and high-molecular-weight kininogen (HK) in plasma of patients with CAP and correlated them to clinical disease severity.

Recommendation for validation and quality assurance of non-invasive prenatal testing for foetal blood groups and implications for IVD risk classification according to EU regulations.

Background And Objectives: Non-invasive assays for predicting foetal blood group status in pregnancy serve as valuable clinical tools in the management of pregnancies at risk of detrimental consequences due to blood group antigen incompatibility. To secure clinical applicability, assays for non-invasive prenatal testing of foetal blood groups need to follow strict rules for validation and quality assurance. Here, we present a multi-national position paper with specific recommendations for validation and quality assurance for such assays and discuss their risk classification according to EU regulations.

Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study.

The early administration of fibrinogen has gained wide acceptance for the treatment of major hemorrhage, whereas the substitution of coagulation factor XIII (FXIII) is only supported by a low level of evidence. This study aimed to answer the question of whether a combined therapy of fibrinogen/FXIII substitution performs superiorly to sole fibrinogen administration in the treatment of dilutional coagulopathy. An in-vitro model of massive transfusion was used to compare the effect of combined fibrinogen/FXIII administration to that of sole fibrinogen therapy for the treatment of dilutional coagulopathy.

Characterization of CD177-reactive iso- and auto-antibodies.

Background: CD177 is a surface protein on neutrophils and a main mediator for the surface expression of proteinase 3 (PR3). Its functions are largely unknown. At least three types of antibodies have been described to target CD177: isoantibodies, which are formed in CD177-null individuals as a result of an immune reaction following transfusion or pregnancy; autoantibodies present in sera from patients with autoimmune neutropenia; and antineutrophil cytoplasmic antibodies in sera from patients with glomerulonephritis with polyangiitis.

Immunization against α β and α β in Glanzmann thrombasthenia patients carrying the French Gypsy mutation.

Essentials The c.1544+1G>A mutation was identified in Gypsy Glanzmann thrombasthenia (GT) patients. Gypsy GT patients express normal α β carrying HPA-1b epitopes.

Incidental diagnosis of leukocyte adhesion deficiency type II following ABO typing.

Individuals with the Bombay phenotype (Oh) in the ABO blood group system do not express the H, A, and B antigens but have no clinical symptoms. Bombay phenotype with clinical symptoms has been described in leukocyte adhesion deficiency type II (LAD II), a fucosylation disorder caused by mutations in SLC35C1. Only few LAD II patients have been described so far.

Decreased Thymic Output Contributes to Immune Defects in Septic Patients.

Background: Prolonged immunosuppression and hypoinflammation, termed compensatory anti-inflammatory response syndrome (CARS), contribute to high morbidity and mortality in the late phase of sepsis. Although apoptosis is a well-known cause of lymphopenia in sepsis, the contribution of thymic output to immune alterations in sepsis and potential compensatory mechanisms are largely unknown.

Methods: We investigate the release of CD4+ T cells from the thymus and their peripheral proliferation by evaluating T-cell receptor excision circles (TREC) and the expression of CD31 as markers for recent thymic emigrants (RTE) and their proliferative offspring in septic patients with relevant lymphopenia in the CARS phase.

Naturally occurring point mutation Cys460Trp located in the I-EGF1 domain of integrin β3 alters the binding of some anti-HPA-1a antibodies.

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by the destruction of platelets in the fetus or newborn by maternal platelet alloantibodies, mostly against human platelet antigen (HPA)-1a. Recent studies indicate that two anti-HPA subtypes exist: Type I reacts with epitopes residing on the plexin-semaphorin-integrin (PSI) and type II with plexin-semaphorin-integrin/integrin epidermal growth factor 1 (I-EGF1) domains of the β3 integrin. Here, we evaluated whether a Cys460Trp mutation in the I-EGF1 domain found in a patient with Glanzmann thrombasthenia can alter the binding of anti-HPA-1a.

Non-invasive risk-assessment and bleeding prophylaxis with IVIG in pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia: management to minimize adverse events.

Introduction: In pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia (FNAIT), prenatal intervention in subsequent pregnancies may be required to prevent fetal bleeding. Several invasive and non-invasive protocols have been published: amniocentesis for fetal genotyping, fetal blood sampling for the determination of fetal platelet count, intrauterine platelet transfusions, and weekly maternal i.v.

Potential of Next-Generation Sequencing in Noninvasive Fetal Molecular Blood Group Genotyping.

Hemolytic disease of the fetus and newborn and fetal and neonatal alloimmune thrombocytopenia are caused by maternal antibodies against fetal alloantigens on red blood cells or platelets that are inherited from the father. After transplacental transport to the fetal circulation, antibodies of the IgG class may cause severe fetal anemia or bleeding complications. The indication for noninvasive fetal blood group genotyping is given if a clinically relevant antibody is detected in a pregnant woman and if the father is heterozygous (or unknown) for the implicated blood group allele.

Primary structure of human neutrophil antigens 1a and 1b.

Background: Neutrophil specific Fcγ receptor IIIb (CD16b) is a low-affinity IgG receptor. Its polymorphic variants are associated with human neutrophil antigens (HNA). HNA-1a and HNA-1b differ in four amino acids.

Targeted antenatal anti-D prophylaxis for RhD-negative pregnant women: a systematic review.

Background: All non-sensitized Rhesus D (RhD)-negative pregnant women in Germany receive antenatal anti-D prophylaxis without knowledge of fetal RhD status. Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma could avoid unnecessary anti-D administration. In this paper, we systematically reviewed the evidence on the benefit of NIPT for fetal RhD status in RhD-negative pregnant women.