A Novel STK4 Mutation Impairs T Cell Immunity Through Dysregulation of Cytokine-Induced Adhesion and Chemotaxis Genes

• DOI: 10.1007/s10875-021-01115-2
• Publication Date: 2021-08-24T09:04:20Z
• Authors: Andrea Guennoun; Salim Bougarn; Taushif Khan; Rafah Mackeh; Mahbuba Rahman; Fatima Al-Ali; Manar Ata; Waleed Aamer; Debra Prosser; Tanwir Habib; Evonne Chin-Smith; Khawla Al-Darwish; Qian Zhang; Alya Al-Shakaki; Amal Robay; Ronald G. Crystal; Khalid Fakhro; Amal Al-Naimi; Eman Al Maslamani; Amjad Tuffaha; Ibrahim Janahi; Mohammad Janahi; Donald R. Love; Mohammed Yousuf K...; Bernice Lo; Amel Hassan; Mehdi Adeli; Nico Marr
• Keywords: Male; 0301 basic medicine; Epstein-Barr Virus Infections; Chemotaxis; T-Lymphocytes; FOS: Clinical medicine; Immunology; Immunologic Deficiency Syndromes; Intracellular Signaling Peptides and Proteins; Dendritic Cells; Protein Serine-Threonine Kinases; Antibodies, Viral; Antibodies, Bacterial; 3. Good health; Killer Cells, Natural; 03 medical and health sciences; Mutation; Cell Adhesion; Cytokines; Humans; Original Article; Transcriptome; Tuberculosis, Pulmonary

Human serine/threonine kinase 4 (STK4) deficiency is a rare, autosomal recessive genetic disorder leading to combined immunodeficiency; however, the extent which immune signaling and host defense are impaired unclear. We assessed functional consequences of novel, homozygous nonsense STK4 mutation (NM_006282.2:c.871C > T, p.Arg291*) identified in pediatric patient by comparing his innate adaptive cell-mediated humoral responses with those three heterozygous relatives unrelated controls.The etiology was verified whole genome Sanger sequencing. gene protein expression measured quantitative RT-PCR immunoblotting, respectively. Cellular abnormalities were high-throughput RT-RCR, RNA-Seq, ELISA, flow cytometry. Antibody ELISA phage immunoprecipitation-sequencing.The exhibited partial loss complete function recurrent viral bacterial infections, notably persistent Epstein-Barr virus viremia pulmonary tuberculosis. molecular analyses revealed abnormal fractions T cell subsets, plasmacytoid dendritic cells, NK cells. The transcriptional patient's blood PBMC samples indicated dysregulated interferon signaling, immunity, increased apoptosis as well regulation cytokine-induced adhesion leukocyte chemotaxis genes. Nonetheless, had detectable vaccine-specific antibodies IgG various pathogens, consistent normal CD19 + B fraction, albeit distinctive antibody repertoire, largely driven herpes antigens.Patients can exhibit broad impairment extending beyond lymphoid