Schimke immuno-osseous dysplasia is a rare multisystemic disorder caused by biallelic loss of function of the SMARCAL1 gene that plays a pivotal role in replication fork stabilization and thus DNA repair. Individuals affected from this disease suffer from disproportionate growth failure, steroid resistant nephrotic syndrome leading to renal failure and primary immunodeficiency mediated by T cell lymphopenia. With infectious complications being the leading cause of death in this disease, researching the nature of the immunodeficiency is crucial, particularly as the state is exacerbated by loss of antibodies due to nephrotic syndrome or immunosuppressive treatment. Building on previous findings that identified the loss of IL-7 receptor expression as a possible cause of the immunodeficiency and increased sensitivity to radiation-induced damage, we have employed spectral cytometry and multiplex RNA-sequencing to assess the phenotype and function of T cells ex-vivo and to study changes induced by in-vitro UV irradiation and reaction of cells to the presence of IL-7. Our findings highlight the mature phenotype of T cells with proinflammatory Th1 skew and signs of exhaustion and lack of response to IL-7. UV light irradiation caused a severe increase in the apoptosis of T cells, however the expression of the genes related to immune response and regulation remained surprisingly similar to healthy cells. Due to the disease's rarity, more studies will be necessary for complete understanding of this unique immunodeficiency.

• Keywords
• Cytometry, Exhaustion, IL-7, Immunodeficiency, Lymphopenia, Peritoneal dialysis, RNA-seq, SIOD, Schimke Imunoosseous dysplasia, Schimke immuno-osseous dysplasia, Spectral Cytometry, T cell, Thymus,
• MeSH
• Apoptosis genetics   MeSH
• Arteriosclerosis genetics   etiology   immunology   MeSH
• Child MeSH
• DNA Helicases genetics   MeSH
• Humans MeSH
• Bone Diseases, Metabolic etiology   genetics   MeSH
• Nephrotic Syndrome etiology   genetics   MeSH
• DNA Repair * genetics   MeSH
• Osteochondrodysplasias * genetics   immunology   MeSH
• Pulmonary Embolism genetics   etiology   MeSH
• Growth Disorders genetics   etiology   MeSH
• Primary Immunodeficiency Diseases * genetics   diagnosis   immunology   MeSH
• Immunologic Deficiency Syndromes genetics   immunology   MeSH
• T-Lymphocytes immunology   MeSH
• Ultraviolet Rays adverse effects   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA Helicases MeSH
• SMARCAL1 protein, human MeSH Browser