Planning antepartum directed donations in preparation for neonatal cardiac surgery in the absence of compatible donors.

Background: Homozygous inheritance of the R haplotype, characterized by the absence of the high frequency antigen Sec, as well as partial C and e antigens, is rare and is associated with potential for alloimmunization. Anti-Sec has been reported to be associated with a risk of delayed hemolytic transfusion reaction and hemolytic disease of the fetus and newborn (HDFN).

Results: We report the case of a 36-year-old pregnant woman with known sickle cell trait (SCT) and homozygous for the R haplotype with anti-Sec, anti-c, and anti-e.

Transfusing children with sickle cell disease using blood group genotyping when the pool of Black donors is limited.

Background: Red blood cell transfusion is an effective treatment for patients with sickle cell disease (SCD). Alloimmunization can occur after a single transfusion, limiting further usage of blood transfusion. It is recommended to match for the ABO, D, C, E, and K antigens to reduce risks of alloimmunization.

Management of a patient with sickle cell disease and multiple red blood cell alloantibodies in preparation for a hematopoietic stem cell transplantation.

Background: Hematopoietic stem cell transplant (HSCT) is currently the only widely available curative option for patients with sickle cell disease (SCD). Alloimmunization in this population is frequent and can complicate transfusion management during the HSCT period. The case of a pediatric patient with severe SCD clinical phenotype, multiple alloantibodies (9), and hyperhemolysis syndrome who underwent haploidentical HSCT is described.

Incidence of acute haemolytic transfusion reaction among ABO-incompatible recipients transfused with A blood: A case series.

Background And Objectives: ABO antigens are among the most immunogenic, but the haemolytic risks of ABO incompatibilities involving a donor with a weak ABO phenotype are little documented.

Materials And Methods: This retrospective case series assessed the incidence of acute haemolytic transfusion reaction (AHTR) among ABO-incompatible recipients of A blood in Québec (Canada). Transfusion safety officers reported laboratory AHTR indicators measured ≤24 h pre- and post-transfusion.

HLA and red blood cell antigen genotyping in SARS-CoV-2 convalescent plasma donors.

More data is required regarding the association between HLA allele and red blood cell (RBC) antigen expression in regard to SARS-CoV-2 infection and COVID-19 susceptibility. ABO, RhD, 37 other RBC antigens and HLA-A, B, C, DRB1, DQB1 and DPB1 were determined using high throughput platforms in 90 Caucasian convalescent plasma donors. The AB group was significantly increased (1.

Weak D type 42: Antigen density and risk of alloimmunization in the province of Québec.

Background And Objectives: A high proportion of suspected weak D patients referred to Héma-Québec were genotyped as weak D type 42 (368/2105, 17.5%). These patients are currently considered D with regard to RhD immunoprophylaxis in pregnancy and transfusion.

High prevalence of weak D type 42 in a large-scale RHD genotyping program in the province of Quebec (Canada).

Background: The determination of the RhD phenotype is crucial to avoid alloimmunization, especially in childbearing women. Following the 2015 recommendation from the Work Group on RHD Genotyping, a large-scale RHD genotyping program was implemented in the province of Quebec (Canada) and offered to women ≤45 years old with a serological weak D or discordant results. Since weak D type 42 was previously shown to be prevalent among French Canadians, genotyping for that variant was also performed.

A point mutation in the linker domain of mouse STAT5A is associated with impaired NK-cell regulation.

The transcription factor STAT5 is critical for peripheral NK-cell survival, proliferation, and cytotoxic function. STAT5 refers to two highly related proteins, STAT5A and STAT5B. In this study, we verified the importance of STAT5A isoform for NK cells.

-Dependent Immune and Central Nervous System Mechanisms Control Viral Replication and Inflammation during Mouse Herpes Simplex Encephalitis.

Herpes simplex encephalitis (HSE), caused by HSV type 1 (HSV-1) infection, is an acute neuroinflammatory condition of the CNS and remains the most common type of sporadic viral encephalitis worldwide. Studies in humans have shown that susceptibility to HSE depends in part on the genetic make-up of the host, with deleterious mutations in the TLR3/type I IFN axis underlying some cases of childhood HSE. Using an in vivo chemical mutagenesis screen for HSV-1 susceptibility in mice, we identified a susceptible pedigree carrying a causal truncating mutation in the gene ( ), encoding for the NF-κB transcription factor subunit c-Rel.

The mitochondrial protease HtrA2 restricts the NLRP3 and AIM2 inflammasomes.

Activation of the inflammasome pathway is crucial for effective intracellular host defense. The mitochondrial network plays an important role in inflammasome regulation but the mechanisms linking mitochondrial homeostasis to attenuation of inflammasome activation are not fully understood. Here, we report that the Parkinson's disease-associated mitochondrial serine protease HtrA2 restricts the activation of ASC-dependent NLRP3 and AIM2 inflammasomes, in a protease activity-dependent manner.

Discovery of Variants Underlying Host Susceptibility to Virus Infection Using Whole-Exome Sequencing.

The clinical course of any viral infection greatly differs in individuals. This variation results from various viral, host, and environmental factors. The identification of host genetic factors influencing inter-individual variation in susceptibility to several pathogenic viruses has tremendously increased our understanding of the mechanisms and pathways required for immunity.

USP15 regulates type I interferon response and is required for pathogenesis of neuroinflammation.

Genes and pathways in which inactivation dampens tissue inflammation present new opportunities for understanding the pathogenesis of common human inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. We identified a mutation in the gene encoding the deubiquitination enzyme USP15 (Usp15) that protected mice against both experimental cerebral malaria (ECM) induced by Plasmodium berghei and experimental autoimmune encephalomyelitis (EAE). Combining immunophenotyping and RNA sequencing in brain (ECM) and spinal cord (EAE) revealed that Usp15-associated resistance to neuroinflammation was linked to dampened type I interferon responses in situ.

An N-ethyl-N-nitrosourea (ENU)-induced dominant negative mutation in the JAK3 kinase protects against cerebral malaria.

Cerebral malaria (CM) is a lethal neurological complication of malaria. We implemented a genome-wide screen in mutagenized mice to identify host proteins involved in CM pathogenesis and whose inhibition may be of therapeutic value. One pedigree (P48) segregated a resistance trait whose CM-protective effect was fully penetrant, mapped to chromosome 8, and identified by genome sequencing as homozygosity for a mis-sense mutation (W81R) in the FERM domain of Janus-associated kinase 3 (Jak3).

Quantitative trait locus analysis, pathway analysis, and consomic mapping show genetic variants of Tnni3k, Fpgt, or H28 control susceptibility to viral myocarditis.

Coxsackievirus B3 (CVB3) infection is the most common cause of viral myocarditis. The pathogenesis of viral myocarditis is strongly controlled by host genetic factors. Although certain indispensable components of immunity have been identified, the genes and pathways underlying natural variation between individuals remain unclear.

Differential importance of highly conserved residues in UL24 for herpes simplex virus 1 replication in vivo and reactivation.

The UL24 gene of herpes simplex virus 1 (HSV-1) is widely conserved among all subfamilies of the Herpesviridae. It is one of only four HSV-1 genes for which mutations have been mapped that confer a syncytial plaque phenotype. In a mouse model of infection, UL24-deficient viruses exhibit reduced titres, particularly in neurons, and an apparent defect in reactivation from latency.

Conserved residues in the UL24 protein of herpes simplex virus 1 are important for dispersal of the nucleolar protein nucleolin.

The UL24 family of proteins is widely conserved among herpesviruses. We demonstrated previously that UL24 of herpes simplex virus 1 (HSV-1) is important for the dispersal of nucleolin from nucleolar foci throughout the nuclei of infected cells. Furthermore, the N-terminal portion of UL24 localizes to nuclei and can disperse nucleolin in the absence of any other viral proteins.