Gut Immunomodulation with Vedolizumab prior to Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients with Inflammatory Bowel Disease.

Inborn errors of immunity (IEI) are often associated with inflammatory bowel disease (IBD). IEI can be corrected by allogeneic hematopoietic stem cell transplantation (HSCT); however, peritransplantation intestinal inflammation may increase the risk of gut graft-versus-host disease (GVHD). Vedolizumab inhibits the homing of lymphocytes to the intestine and may attenuate gut GVHD, yet its role in preventing GVHD in pediatric patients with IEI-associated IBD has not been studied.

Epigenetic and immunological indicators of IPEX disease in subjects with FOXP3 gene mutation.

Background: Forkhead box protein 3 (FOXP3) is the master transcription factor in CD4CD25CD127 regulatory T (Treg) cells. Mutations in FOXP3 result in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome. Clinical presentation of IPEX syndrome is broader than initially described, challenging the understanding of the disease, its evolution, and treatment choice.

Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%).

Progressive decline of T and B cell numbers and function in a patient with CDC42 deficiency.

Single allele mutations in the Cell Division Control protein 42 homolog (CDC42) gene were recently shown to cause Takenouchi-Kosaki syndrome with diverse manifestations. These include persistent mild thrombocytopenia with large platelet size, severe developmental delay, growth retardation, facial dysmorphism, and other neurodevelopmental and hematological anomalies. CDC42 deficiency might also cause myelofibrosis, myeloproliferation, and severe autoinflammation.

Long-Term Outcome of Adenosine Deaminase-Deficient Patients-a Single-Center Experience.

Purpose: Inherited defects in the adenosine deaminase (ADA) enzyme can cause severe combined immune deficiency (SCID) and systemic abnormalities. Management options for ADA-deficient patients include enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy (GT). Here, we describe the long-term benefits of these treatments.

Novel Combined Immune Deficiency and Radiation Sensitivity Blended Phenotype in an Adult with Biallelic Variations in and .

With the advent of high-throughput genomic sequencing techniques, novel genetic etiologies are being uncovered for previously unexplained Mendelian phenotypes, and the underlying genetic architecture of disease is being unraveled. Although most of these "mendelizing" disease traits represent phenotypes caused by single-gene defects, a percentage of patients have blended phenotypes caused by pathogenic variants in multiple genes. We describe an adult patient with susceptibility to bacterial, herpesviral, and fungal infections.