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.

• Klíčová slova
• Cytometry, Exhaustion, IL-7, Immunodeficiency, Lymphopenia, Peritoneal dialysis, RNA-seq, SIOD, Schimke Imunoosseous dysplasia, Schimke immuno-osseous dysplasia, Spectral Cytometry, T cell, Thymus,
• MeSH
• apoptóza genetika   MeSH
• arterioskleróza genetika   etiologie   imunologie   MeSH
• dítě MeSH
• DNA-helikasy genetika   MeSH
• lidé MeSH
• metabolické nemoci kostí etiologie   genetika   MeSH
• nefrotický syndrom etiologie   genetika   MeSH
• oprava DNA * genetika   MeSH
• osteochondrodysplazie * genetika   imunologie   MeSH
• plicní embolie genetika   etiologie   MeSH
• poruchy růstu genetika   etiologie   MeSH
• primární imunodeficience * genetika   diagnóza   imunologie   MeSH
• syndromy imunologické nedostatečnosti genetika   imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• ultrafialové záření škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA-helikasy MeSH
• SMARCAL1 protein, human MeSH Prohlížeč

Autoimmunity is often observed among individuals with primary immune deficiencies; however, the frequency and role of autoimmunity in Schimke immuno-osseous dysplasia (SIOD) has not been fully assessed. SIOD, which is caused by mutations of SMARCAL1, is a rare autosomal recessive disease with its prominent features being skeletal dysplasia, T cell deficiency, and renal failure. We present a child with severe SIOD who developed rituximab resistant Evans syndrome (ES). Consistent with observations in several other immunodeficiency disorders, a review of SIOD patients showed that approximately a fifth of SIOD patients have some features of autoimmune disease. To our best knowledge this case represents the first patient with SIOD and rituximab resistant ES and the first study of autoimmune disease in SIOD.

• Publikační typ
• časopisecké články MeSH