-
Journal of Pediatric Hematology/oncology Mar 2024Three-year-old boy who presented with colicky abdominal pain, diarrhoea and vomiting was investigated with computed tomography which revealed a mass in the...
Three-year-old boy who presented with colicky abdominal pain, diarrhoea and vomiting was investigated with computed tomography which revealed a mass in the peripancreatic region. An imaging possibility of duodenal intramural hematoma was considered after reassessment with ultrasound which was subsequently confirmed by magnetic resonance imaging. The development of a spontaneous duodenal hematoma lead to further evaluation of the patient and revealed X linked hyper IgM syndrome.
Topics: Male; Humans; Hyper-IgM Immunodeficiency Syndrome, Type 1; Hyper-IgM Immunodeficiency Syndrome; Duodenal Diseases; Duodenum; Gastrointestinal Hemorrhage; Hematoma
PubMed: 37867238
DOI: 10.1097/MPH.0000000000002773 -
Immunogenetics Jun 2024X-linked hyper-immunoglobulin M (X-HIGM) syndrome and autosomal recessive hyper-immunoglobulin E syndrome (HIES) are rare inborn errors of immunity characterized by...
X-linked hyper-immunoglobulin M (X-HIGM) syndrome and autosomal recessive hyper-immunoglobulin E syndrome (HIES) are rare inborn errors of immunity characterized by recurrent infections due to immune system impairment. In this study, we identified a novel hemizygous CD40 ligand (CD40L) mutation and compound heterozygous dedicator of cytokinesis-8 (DOCK8) mutations in two Han Chinese families with X-HIGM and HIES, respectively. We aimed to investigate the association between their genotypes and phenotypes. Genomic DNA was extracted from peripheral blood samples obtained from the families. Whole exome sequencing and Sanger sequencing were performed to identify and verify pathogenic variants in the two families. Clinical analyses of the probands were also performed. A novel hemizygous mutation of CD40L in exon 2 (c.257delA) was identified in the first proband, resulting in the substitution of glycine with glutamic acid at codon 86 of the protein. This leads to premature termination of translation at downstream codon 9 (p.E86Gfs*9). Sanger sequencing confirmed that the variant was inherited from the mother. The second proband carried two novel compound heterozygous mutations in DOCK8: one at exon 14 (c.1546C > G) inherited from the father, and the other at intron 41 (c.5355 + 6C > T; splicing) inherited from the mother. This study enhances our understanding of the pathogenetic mutation spectrum of CD40L and DOCK8 genes, facilitating the prenatal diagnosis of X-HIGM and HIES and enabling timely treatment of patients.
Topics: Humans; Male; Guanine Nucleotide Exchange Factors; CD40 Ligand; Pedigree; Female; Mutation; Heterozygote; Job Syndrome; Hyper-IgM Immunodeficiency Syndrome, Type 1; Asian People; Child; Child, Preschool; China; Exome Sequencing; East Asian People
PubMed: 38587548
DOI: 10.1007/s00251-024-01340-0 -
Cells Feb 2024Selective IgA deficiency (SIgAD) is the most common form and common variable immunodeficiency (CVID) is the most symptomatic form of predominant antibody deficiency....
Selective IgA deficiency (SIgAD) is the most common form and common variable immunodeficiency (CVID) is the most symptomatic form of predominant antibody deficiency. Despite differences in the clinical picture, a similar genetic background is suggested. A common feature of both disorders is the occurrence of autoimmune conditions. Regulatory T cells (T) are the major immune cell type that maintains autoimmune tolerance. As the different types of abnormalities of T cells have been associated with autoimmune disorders in primary immunodeficiency (PID) patients, in our study we aimed to analyze the gene expression profiles of T cells in CVID and SIgAD patients compared to age-matched healthy controls. The transcriptome-wide gene profiling was performed by microarray technology. As a result, we analyzed and visualized gene expression patterns of isolated population of T cells. We showed the differences at the gene level between patients with and without autoimmunizations. Our findings suggest that the gene signatures of T cells isolated from SIgAD and CVID patients differ from age-matched healthy controls and from each other, presenting transcriptional profiles enriched in innate immune or Th response, respectively. The occurrence of autoimmunity in both types of PID is associated with down-regulation of class I IFNs signaling pathways. In summary, our findings improve our understanding of T dysfunctions in patients with common PIDs and associated autoimmunity.
Topics: Child; Humans; Autoimmune Diseases; Common Variable Immunodeficiency; IgA Deficiency; T-Lymphocytes, Regulatory; Transcriptome
PubMed: 38474381
DOI: 10.3390/cells13050417 -
Journal of Pediatric Health Care :... 2024This case describes a four-month-old male who was admitted to the pediatric intensive care unit for acute respiratory failure in the setting of a co-infection requiring...
Use of Metagenomic Next-Generation Sequencing in the Identification of Pneumocystis Jiroveci Pneumonia in a Previously Healthy Infant Diagnosed With X-Linked Hyper-IgM Syndrome.
This case describes a four-month-old male who was admitted to the pediatric intensive care unit for acute respiratory failure in the setting of a co-infection requiring increased ventilatory support. Immunodeficiency workup demonstrated poor vaccination response and low immunoglobulin titers. mNGS via Karius® test was positive for Pneumocystis jiroveci (PJP), Parvovirus, and Bocavirus. The patient was successfully treated with trimethoprim-sulfamethoxazole and prednisone. Genetic workup via Invitae panel confirmed that the patient had X-linked Hyper-IgM Syndrome. Use of mNGS can help with early identification of pathogens that conventional testing does not detect, even in patients not already identified as immunocompromised.
Topics: Humans; Male; Pneumonia, Pneumocystis; Pneumocystis carinii; Infant; Hyper-IgM Immunodeficiency Syndrome, Type 1; High-Throughput Nucleotide Sequencing; Metagenomics; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 38032574
DOI: 10.1016/j.pedhc.2023.09.009