Divergent CD4 T-cell profiles are associated with anti-HLA alloimmunization status in platelet-transfused AML patients.

Introduction: Acute myeloid leukemia (AML) is one of the commonest hematologic disorders. Due to the high frequency of disease- or treatment-related thrombocytopenia, AML requires treatment with multiple platelet transfusions, which can trigger a humoral response directed against platelets. Some, but not all, AML patients develop an anti-HLA immune response after multiple transfusions.

World human neutrophil antigens investigation survey.

Background And Objectives: Human neutrophil antigens (HNAs) are categorized into five systems: HNA-1 to HNA-5. Given the importance of neutrophils in immunity, we sought to create awareness of the role of HNA diagnostic services in managing immune neutropenia and transfusion-related acute lung injury. To provide health communities all around the world with access to these services, we conducted a survey to create a directory of these HNA diagnostic services.

Chronic neutropenia: how best to assess severity and approach management?

Introduction: Neutropenia is a relatively common finding in medical practice and the medical approach requires a gradual and pertinent diagnostic procedure as well as adapted management.

Areas Covered: The area of chronic neutropenia remains fragmented between diverse diseases or situations. Here physicians involved in different aspects of chronic neutropenia gather both the data from medical literature till the end of May 2021 and their experience to offer a global approach for the diagnosis of chronic neutropenia as well as their medical care.

New molecular basis associated with CD36-negative phenotype in the sub-Saharan African population.

Background: CD36 glycoprotein is expressed by various cell types, including platelets (PLTs), monocytes, and erythroid precursors, and is also the receptor for several ligands. However, absence of CD36 expression seems asymptomatic and is poorly described in Caucasians. In contrast, the frequency reaches 7% and 11% in African Caribbean and Asian persons, respectively.

Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase 2b trial.

B-cell activating factor may be involved in the failure of B-cell depleting therapy with rituximab in immune thrombocytopenia (ITP) by promoting the emergence of splenic long-lived plasma cells. From results obtained in mouse models, we hypothesized that combining rituximab with sequential injections of belimumab could increase the rate of response at one year in patients with persistent or chronic ITP by preventing the emergence of these long-lived plasma cells. The study was a single-center, single arm, prospective phase 2b trial (RITUX-PLUS, NCT03154385) investigating the safety and efficacy of rituximab given at a fixed dose of 1,000 mg, two weeks apart, combined with five infusions of belimumab, 10 mg/kg at week 0 (W0)+2 days, W2+2 days, W4, W8 and W12 for adults with primary persistent or chronic ITP.

Severe Transitory Neonatal Neutropenia Associated with Maternal Autoimmune or Idiopathic Neutropenia.

Purpose: Neonatal immune neutropenia is observed in rare cases in newborns from mothers with idiopathic or autoimmune neutropenia, secondary to passive transfer of maternal granulocyte auto-antibodies.

Methods: We performed a literature review and report four supplementary cases from the French registry of neutropenia.

Results: Only 14 cases (11 mothers, 14 newborns) have been reported.

Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study.

Background: Anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies are novel immunotherapies for cancer that can induce immune-related adverse events (irAEs). These adverse events can involve all organs, including the haemopoietic system. Thus far, haematological irAEs (haem-irAEs) have not been extensively characterised.

Perioperative management of a patient with Glanzmann thrombasthenia undergoing a coronary artery bypass graft surgery: a case report.

: We report herein the successful perioperative management of a 57-year-old man with a type I Glanzmann thrombasthenia undergoing coronary artery bypass graft surgery and right carotid endarterectomy. The patient suffered from several lesions in the three major coronary arteries and in the right carotid necessitating surgery. Prophylactic human leukocyte antigen (HLA)-matched platelets transfusions were continuous administrated before, and through the immediate perioperative period.

Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage.

Background: In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most frequently caused by maternal alloimmunization against the human platelet antigen HPA-1a. The most serious complication of severe FNAIT is intracranial hemorrhage (ICH). ICH mainly occurs in utero; therefore, there is a need to identify noninvasive predictive factors of ICH to facilitate early identification of this condition and to determine response to maternal therapy.

Severe chronic primary neutropenia in adults: report on a series of 108 patients.

Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date. We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multi-institutional observational study. Severe CPN adults were mostly female (78%), and median age at diagnosis was 28.

Anti-TNF-α therapy may cause neonatal neutropenia.

Although anti-tumor necrosis factor (anti-TNF) antibodies are associated with a clear risk of agranulocytosis in adults and are known to cross the placenta, monitoring of the absolute neutrophil count (ANC) in neonates born to mothers receiving these biological agents is not currently recommended. Here, we report on the first case series of 4 newborn patients with severe neutropenia born to mothers treated for ulcerative colitis with infliximab during pregnancy (including the third trimester). The newborns presented with severe neutropenia at birth, which was subsequently complicated by skin infections.

Fetal intracranial hemorrhage related to maternal autoimmune thrombocytopenic purpura.

Background: Maternal autoimmune thrombocytopenic purpura (AITP) can cause fetal intracranial hemorrhage.

Case Report: A 19-year-old primigravida was referred to our institution for prenatally detected ventriculomegaly at 30th week of gestation. Her personal and family histories were unremarkable.

Antiplatelet antibodies detected by the MAIPA assay in newly diagnosed immune thrombocytopenia are associated with chronic outcome and higher risk of bleeding.

Immune thrombocytopenia (ITP) results in part from the presence of platelet antibodies, which can be demonstrated by the Monoclonal Antibody-Specific Immobilization of Platelet Antigens (MAIPA) assay. The aim of our study was to correlate the presence of antiplatelet autoantibodies and the natural history of ITP. We performed a retrospective, single-center study of 108 adults with newly diagnosed ITP who had indirect MAIPA assay performed at disease onset.

Primary hematopoietic cells from DBA patients with mutations in RPL11 and RPS19 genes exhibit distinct erythroid phenotype in vitro.

Diamond-Blackfan anemia (DBA) is caused by aberrant ribosomal biogenesis due to ribosomal protein (RP) gene mutations. To develop mechanistic understanding of DBA pathogenesis, we studied CD34⁺ cells from peripheral blood of DBA patients carrying RPL11 and RPS19 ribosomal gene mutations and determined their ability to undergo erythroid differentiation in vitro. RPS19 mutations induced a decrease in proliferation of progenitor cells, but the terminal erythroid differentiation was normal with little or no apoptosis.

The hydration state of human red blood cells and their susceptibility to invasion by Plasmodium falciparum.

In most inherited red blood cell (RBC) disorders with high gene frequencies in malaria-endemic regions, the distribution of RBC hydration states is much wider than normal. The relationship between the hydration state of circulating RBCs and protection against severe falciparum malaria remains unexplored. The present investigation was prompted by a casual observation suggesting that falciparum merozoites were unable to invade isotonically dehydrated normal RBCs.

Congenital anerythremic erythroleukemia presenting as hepatic failure.

We report an atypical case of congenital erythroleukemia in a child born with hepatosplenomegaly and abnormal liver tests. The initial peripheral blood cell count showed anemia and hyperleukocytosis with erythroblastosis that disappeared 1 week later. During the next 5 weeks, no blasts were found in the blood, and less than 5% were found on 2 successive bone marrow aspirates.

A splicing alteration of 4.1R pre-mRNA generates 2 protein isoforms with distinct assembly to spindle poles in mitotic cells.

The C-terminal region of erythroid cytoskeletal protein 4.1R, encoded by exons 20 and 21, contains a binding site for nuclear mitotic apparatus protein (NuMA), a protein needed for the formation and stabilization of the mitotic spindle. We have previously described a splicing mutation of 4.

[Noninfectious febrile inflammatory syndromes in children: diagnosis and usefulness of diagnostic procedures].

Objective: To determine the causes and to quantify the benefits obtained from further diagnostic investigations in children presenting with a non infectious inflammatory fever.

Methods: The records of 62 children aged from two-months to 15 years (median: four years) admitted to a paediatric department between 1990 and 2000 for the evaluation of a fever associated to an inflammatory syndrome, defined as temperature over 38 degrees C with an increase of the erythrocyte sedimentation rate (ESR) more than 20 mm/h and/or a serum C-reactive protein level (CRP) > 20 mg/L, and excluding overt infectious diseases, were retrospectively reviewed.

Results: Of these patients, 79% children (49 cases) had inflammatory systemic disease, 3.

Paradoxical secondary polycythemia in von Hippel-Lindau patients treated with anti-vascular endothelial growth factor receptor therapy.

Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome caused by germline mutations in the VHL tumor-suppressor gene. Central nervous system (CNS) and retinal hemangioblastomas are highly vascular tumors that are hallmarks of the disease. These tumors overexpress vascular endothelial growth factor (VEGF) and represent a potential target for anti-angiogenic drugs.

[Erythropoiesis disorders and other central autoimmune anemias].

Immune-mediated acquired disorders of erythropoiesis can result in pure red cell aplasia or ineffective erythropoiesis. Erythropoiesis can be suppressed or impaired by humoral or cellular mechanisms. In vitro inhibition of erythroid colony growth by humoral factors or lymphocytes is a strong argument for the immune origin of the disease.

Autoimmune disorders of erythropoiesis.

Immune-mediated disorders of erythropoiesis can result in acquired severe anemia, low reticulocyte counts, and bone marrow exhibiting pure red cell aplasia or ineffective erythropoiesis. Erythropoiesis can be suppressed or impaired by humoral or cellular mechanisms. In vitro inhibition of erythroid colony growth by immunoglobulins or lymphocytes can be a strong argument for the immune origin of the disease.

Dyserythropoiesis associated with a fas-deficient condition in childhood.

Defective lymphocyte apoptosis caused by mutations of the Fas gene can result in an autoimmune lymphoproliferative syndrome (ALPS) in humans. We report two cases of dyserythropoiesis associated with a Fas-deficient condition in childhood. In both cases, dyserythropoiesis predominated on the more mature erythroblasts, and was associated with a lymphoproliferative syndrome as well as with haemolytic anaemia, hypergammaglobulinaemia and the expansion of an unusual population of CD4- CD8- T cells that express the alpha/beta T-cell receptor.