LTβR deficiency causes lymph node aplasia and impaired B cell differentiation.

Secondary lymphoid organs (SLOs) provide the confined microenvironment required for stromal cells to interact with immune cells to initiate adaptive immune responses resulting in B cell differentiation. Here, we studied three patients from two families with functional hyposplenism, absence of tonsils, and complete lymph node aplasia, leading to recurrent bacterial and viral infections. We identified biallelic loss-of-function mutations in encoding the lymphotoxin beta receptor (LTβR), primarily expressed on stromal cells.

Delineating the Clinical and Immunologic Characteristics: A Comparative Study of Inborn Errors of Immunity in Adult versus Pediatric Diagnosed.

Introduction: Inborn errors of immunity (IEIs) are rare genetic disorders primarily identified in children due to their significant effects on immune system functionality. However, an increasing number of IEI cases are being diagnosed in adults, attributed to delayed presentation or advancements in diagnostic capabilities. This study explores the clinical and immunologic distinctions between IEIs diagnosed in adulthood versus childhood, shedding light on their differential presentations, the impact of diagnostic delays, and treatment outcomes.

DIAPH1-Deficiency is Associated with Major T, NK and ILC Defects in Humans.

Loss of function mutations in Diaphanous related formin 1 (DIAPH1) are associated with seizures, cortical blindness, and microcephaly syndrome (SCBMS) and are recently linked to combined immunodeficiency. However, the extent of defects in T and innate lymphoid cells (ILCs) remain unexplored. Herein, we characterized the primary T, natural killer (NK) and helper ILCs of six patients carrying two novel loss of function mutation in DIAPH1 and Jurkat cells after DIAPH1 knockdown.

MHC Class II Deficiency: Clinical, Immunological, and Genetic Insights in a Large Multicenter Cohort.

Background: Major histocompatibility complex class II deficiency, a combined immunodeficiency, results from loss of HLA class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation stands as the sole curative approach, although factors influencing patient outcomes remain insufficiently explored.

Objectives: To elucidate the clinical, immunologic, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates.

Artemis deficiency: A large cohort including a novel variant with increased radiosensitivity.

Background: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented.

Methods: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively.

Neurocognitive Impairment in Patients With Ataxia Telangiectasia and Their Unaffected Parents: Is It Similar?

Background: Ataxia telangiectasia (AT) is a genetic multisystemic disorder affecting the nervous system. Data on neurocognitive functioning in AT are limited and focused on patients at various stages of disease. Because of the genetic nature of the disorder, parents of patients may also display subtle neurological problems.

Rapamycin Controls Lymphoproliferation and Reverses T-Cell Responses in a Patient with a Novel STIM1 Loss-of-Function Deletion.

Purpose: Deficiency of stromal interaction molecule 1 (STIM1) results in combined immunodeficiency accompanied by extra-immunological findings like enamel defects and myopathy. We here studied a patient with a STIM1 loss-of-function mutation who presented with severe lymphoproliferation. We sought to explore the efficacy of the mTOR inhibitor rapamycin in controlling disease manifestations and reversing aberrant T-cell subsets and functions, which has never been used previously in this disorder.

Regulatory T-cell dysfunction and cutaneous exposure to Staphylococcus aureus underlie eczema in DOCK8 deficiency.

Background: Dedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD).

Objective: We sought to understand the mechanisms of eczema in DOCK8 deficiency.

Methods: Skin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression.

Evaluation of Clinical and Immunological Alterations Associated with ICF Syndrome.

Purpose: Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive combined immunodeficiency. The detailed immune responses are not explored widely. We investigated known and novel immune alterations in lymphocyte subpopulations and their association with clinical symptoms in a well-defined ICF cohort.

Clinical and immunological outcomes of SARS-CoV-2 infection in patients with inborn errors of immunity receiving different brands and doses of COVID-19 vaccines.

Introduction: Vaccines against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) provide successful control of the coronavirus-2019 (COVID-19) pandemic. The safety and immunogenicity studies are encouraging in patients with inborn errors of immunity (IEI); however, data about mortality outcomes and severe disease after vaccination still need to be fully addressed. Therefore, we aimed to determine the clinical and immunological outcomes of SARS-CoV-2 infection in patients with IEI who have received vaccination.