JAK/STAT defects and immune dysregulation, and guiding therapeutic choices.

Inborn errors of immunity (IEIs) encompass a diverse spectrum of genetic disorders that disrupt the intricate mechanisms of the immune system, leading to a variety of clinical manifestations. Traditionally associated with an increased susceptibility to recurrent infections, IEIs have unveiled a broader clinical landscape, encompassing immune dysregulation disorders characterized by autoimmunity, severe allergy, lymphoproliferation, and even malignancy. This review delves into the intricate interplay between IEIs and the JAK-STAT signaling pathway, a critical regulator of immune homeostasis.

Implementing a Disease-specific Multidisciplinary Team and Order Set for Hemophagocytic Lymphohistiocytosis in a Pediatric Hospital.

Objective: To improve outcomes of hemophagocytic lymphohistiocytosis (HLH), prompt recognition and treatment are necessary. A HLH multidisciplinary team was implemented at our institution, and we established an electronic order set to foster uniformity in the diagnostic approach. The goal of this study is to capture the impact of this diagnostic tool.

Cord blood transplantation for nonmalignant disorders: early functional immunity and high survival.

There is no consensus on the best donor for children with nonmalignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We evaluated the 2-year overall survival (OS) after umbilical cord blood transplantation (UCBT) in patients with nonmalignant disorders from 2009 to 2020 enrolled in a prospective clinical trial using either 5/6 or 6/6 UCB as the cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy.

Infections in Infants with SCID: Isolation, Infection Screening, and Prophylaxis in PIDTC Centers.

Purpose: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children with severe combined immunodeficiency (SCID) in a prospective natural history study of hematopoietic stem cell transplant (HSCT) outcomes over the last decade. Despite newborn screening (NBS) for SCID, infections occurred prior to HSCT. This study's objectives were to define the types and timing of infection prior to HSCT in patients diagnosed via NBS or by family history (FH) and to understand the breadth of strategies employed at PIDTC centers for infection prevention.

Human diseases caused by impaired signal transducer and activator of transcription and Janus kinase signaling.

Purpose Of Review: The Janus kinase (JAK) and signal transducer of activation (STAT) pathway plays a key role in the immune system. It is employed by diverse cytokines, interferons, growth factors and related molecules. Mutations in JAK/STAT pathway have been implicated in human disease.

Characterization of Transcriptional Regulatory Networks that Promote and Restrict Identities and Functions of Intestinal Innate Lymphoid Cells.

Innate lymphoid cells (ILCs) promote tissue homeostasis and immune defense but also contribute to inflammatory diseases. ILCs exhibit phenotypic and functional plasticity in response to environmental stimuli, yet the transcriptional regulatory networks (TRNs) that control ILC function are largely unknown. Here, we integrate gene expression and chromatin accessibility data to infer regulatory interactions between transcription factors (TFs) and genes within intestinal type 1, 2, and 3 ILC subsets.

A Novel Mutation in a Qatari Patient With Hyper-IgE Syndrome.

Autosomal dominant hyper-IgE syndrome caused by mutations in the transcription factor STAT3 (AD-HIES) is characterized by a collection of immunologic and non-immune features including eczema, recurrent infections, elevated IgE levels, and connective tissue anomalies. We report the case of a Qatari child with a history of recurrent staphylococcal skin infections since infancy, who was found to have a novel, mutation in STAT3 (c.1934T>A, p.

Fyn kinase is required for optimal humoral responses.

The generation of antigen-specific antibodies and the development of immunological memory require collaboration between B and T cells. T cell-secreted IL-4 is important for B cell survival, isotype switch to IgG1 and IgE, affinity maturation, and the development of germinal centers (GC). Fyn, a member of the Src family tyrosine kinase, is widely expressed in many cell types, including lymphocytes.

ADAM10 regulates transcription factor expression required for plasma cell function.

A disintegrin and metalloprotease 10 (ADAM10) is a key regulator of cellular processes by shedding extracellular domains of transmembrane proteins. We have previously demonstrated that deletion of B cell expressed ADAM10 results in changes in lymphoid tissue architecture and impaired germinal center (GC) formation. In this study, mice were generated in which ADAM10 is deleted in B cells following class switch recombination (ADAM10(Δ/Δ)IgG1-cre(+/-) mice).

Lyn but not Fyn kinase controls IgG-mediated systemic anaphylaxis.

Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of FcεRI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage, and neutrophil secretion of platelet-activating factor subsequent to FcγR stimulation by IgG/Ag complexes.

A disintegrin and metalloproteinase 10 regulates antibody production and maintenance of lymphoid architecture.

A disintegrin and metalloproteinase 10 (ADAM10) is a zinc-dependent proteinase related to matrix metalloproteinases. ADAM10 has emerged as a key regulator of cellular processes by cleaving and shedding extracellular domains of multiple transmembrane receptors and ligands. We have developed B cell-specific ADAM10-deficient mice (ADAM10(B-/-)).

The emergence of ADAM10 as a regulator of lymphocyte development and autoimmunity.

Proteolytic processing of transmembrane receptors and ligands can have a dramatic impact on cell signaling processes and subsequent cellular responses, including activation and differentiation. A member of the disintegrin and metalloproteinase family, ADAM10, has emerged as a prominent regulator of numerous receptors and ligands, including Notch and CD23. Here, we review studies resulting from the recent generation of ADAM10 conditional knockout mice which revealed a critical role for ADAM10 in Notch-dependent lymphocyte development.