Efficiency and Health Economic Evaluations of BD OneFlow™ Flow Cytometry Reagents for Diagnosing Chronic Lymphoid Leukemia.

Reason For The Study: To standardize the use of flow cytometry for classifying hematological malignancies and make the results reliable and reproducible across laboratories, the EuroFlow™ Consortium published a comprehensive specification of antibody-fluorochrome conjugates, standard protocols, and algorithms for analysis. The BD OneFlow™ system builds on, and further standardizes, the EuroFlow protocols. We aimed to assess the effects on safety, efficiency, and costs for laboratories of adopting the BD OneFlow reagent tubes (LST and B-CLPD T1) for diagnosing chronic lymphocytic leukemia.

New graft manipulation strategies improve the outcome of mismatched stem cell transplantation in children with primary immunodeficiencies.

Background: Mismatched stem cell transplantation is associated with a high risk of graft loss, graft-versus-host disease (GvHD), and transplant-related mortality. Alternative graft manipulation strategies have been used over the last 11 years to reduce these risks.

Objective: We investigated the outcome of using different graft manipulation strategies among children with primary immunodeficiencies.

T-cell receptor αβ and CD19 cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved with HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft-versus-host disease (GvHD) and rejection associated with such transplants.

Identification of Heterozygous Single- and Multi-exon Deletions in IL7R by Whole Exome Sequencing.

Purpose: We aimed to achieve a retrospective molecular diagnosis by applying state-of-the-art genomic sequencing methods to past patients with T-B+NK+ severe combined immunodeficiency (SCID). We included identification of copy number variations (CNVs) by whole exome sequencing (WES) using the CNV calling method ExomeDepth to detect gene alterations for which routine Sanger sequencing analysis is not suitable, such as large heterozygous deletions.

Methods: Of a total of 12 undiagnosed patients with T-B+NK+ SCID, we analyzed eight probands by WES, using GATK to detect single nucleotide variants (SNVs) and small insertions and deletions (INDELs) and ExomeDepth to detect CNVs.

Dendritic cell analysis in primary immunodeficiency.

Purpose Of Review: Dendritic cells are specialized antigen-presenting cells which link innate and adaptive immunity, through recognition and presentation of antigen to T cells. Although the importance of dendritic cells has been demonstrated in many animal models, their contribution to human immunity remains relatively unexplored in vivo.Given their central role in infection, autoimmunity, and malignancy, dendritic cell deficiency or dysfunction would be expected to have clinical consequences.

Respiratory Health and Related Quality of Life in Patients with Congenital Agammaglobulinemia in the Northern Region of the UK.

Introduction: Patients with congenital agammaglobulinemia, characterized by a defect in B lymphocyte differentiation causing B alymphocytosis, require life-long IgG replacement. There is scant literature regarding the effectiveness of IgG treatment at preventing mucosal (particularly sinopulmonary tract) infection and whether current management adequately restores "normal" health and quality of life (QoL). We aimed to document infective episodes pre- and post-commencing IgG replacement, determine any change in lung function and structure and assess respiratory status and QoL in a cohort of patients treated in Newcastle.

Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency.

Purpose: To investigate the clinical and functional aspects of MST1 (STK4) deficiency in a profoundly CD4-lymphopenic kindred with a novel homozygous nonsense mutation in STK4. Although recent studies have described the cellular effects of murine Mst1 deficiency, the phenotype of MST1-deficient human lymphocytes has yet to be fully explored. Patient lymphocytes were therefore investigated in the context of current knowledge of murine Mst1 deficiency.

Astute Clinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 of ICOS Causes a Combined Immunodeficiency Associated with an Enteritis and Hepatitis.

ICOS encodes the Inducible T-cell Co-Stimulator (ICOS). Deficiency of this receptor in humans causes a common variable immunodeficiency (CVID) characterised by an absence of class-switched memory B cells and hypogammaglobulinemia. Three pathogenic mutations in ICOS have been described to date in a total of 13 cases.

Rapid detection of dendritic cell and monocyte disorders using CD4 as a lineage marker of the human peripheral blood antigen-presenting cell compartment.

Dendritic cells (DCs) and monocytes are critical regulators and effectors of innate and adaptive immune responses. Monocyte expansion has been described in many pathological states while monocyte and DC deficiency syndromes are relatively recent additions to the catalog of human primary immunodeficiency disorders. Clinically applicable screening tests to diagnose and monitor these conditions are lacking.

Immunological characteristics and T-cell receptor clonal diversity in children with systemic juvenile idiopathic arthritis undergoing T-cell-depleted autologous stem cell transplantation.

Children with systemic Juvenile Idiopathic Arthritis (sJIA), the most severe subtype of JIA, are at risk from destructive polyarthritis and growth failure, and corticosteroids as part of conventional treatment can result in osteoporosis and growth delay. In children where there is failure or toxicity from drug therapies, disease has been successfully controlled by T-cell-depleted autologous stem cell transplantation (ASCT). At present, the immunological basis underlying remission after ASCT is unknown.

Low-dose serotherapy improves early immune reconstitution after cord blood transplantation for primary immunodeficiencies.

Cord blood transplantation (CBT) is curative for many primary immunodeficiencies (PIDs) but is associated with risks of viral infection and graft-versus-host disease (GvHD). Serotherapy reduces GvHD but potentially increases the risk of viral infection by delaying immune reconstitution. Because many PID patients have pre-existing viral infections, the optimal dose of serotherapy is unclear.

Phenotypic variations of cartilage hair hypoplasia: granulomatous skin inflammation and severe T cell immunodeficiency as initial clinical presentation in otherwise well child with short stature.

We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. When previously investigated for short stature, and at the time of current investigations, she had no radiological skeletal features characteristics for cartilage hair hypoplasia, but we found a disease causing RMRP (RNase mitochondrial RNA processing endoribonuclease) gene mutation.

Graves' immune reconstitution inflammatory syndrome in childhood.

Background: The use of hematopoietic stem cell transplantations (HSCTs) as a curative therapy for life-threatening immunodeficiencies has had a profound impact on clinical outcomes. A subset of patients may experience immune reconstitution inflammatory syndrome (IRIS) post-transplant affecting the thyroid gland, but this has received little attention in the pediatric literature. We present the clinical, biochemical, and cytological course of patients with Graves' disease after HSCT in the pediatric population.

Mutation in the TCRα subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCRαβ+ T cells.

Inherited immunodeficiency disorders can be caused by mutations in any one of a large number of genes involved in the function of immune cells. Here, we describe two families with an autosomal recessive inherited immunodeficiency disorder characterized by increased susceptibility to infection and autoimmunity. Genetic linkage studies mapped the disorder to chromosomal region 14q11.

Triggering of atypical hemolytic uremic syndrome by influenza A (H1N1).

We report a case of atypical hemolytic uremic syndrome (aHUS) triggered by influenza A (H1N1) in a 17-year-old boy with a mutation in the gene (CD46) encoding the transmembrane complement regulator membrane cofactor protein. The patient recovered completely following treatment with oseltamivir, plasma exchange, and hemodialysis. We describe the case and discuss this unusual association of diseases.

Chronic granulomatous disease presenting as fulminant Aspergillus pneumonitis: a lethal combination?

Objective: Case reports of two patients with unusually late initial presentation of chronic granulomatous disease with fulminant Aspergillus pneumonia.

Data Sources And Extraction: Medical notes; retrospective study.

Study Selection: Identical pattern of clinical presentation in two patients referred for support with extracorporeal membrane oxygenation (ECMO).

Unrelated donor and HLA-identical sibling haematopoietic stem cell transplantation cure chronic granulomatous disease with good long-term outcome and growth.

Chronic granulomatous disease (CGD) causes recurrent infection and inflammatory disease. Despite antimicrobial prophylaxis, patients experience frequent hospitalisations and 50% mortality by 30 years. Haematopoietic stem cell transplantation (HSCT) can cure CGD with resolution of infection and colitis.