RESUMEN
Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7Rα) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7Rα expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients.
Asunto(s)
Arteriosclerosis/genética , Síndromes de Inmunodeficiencia/genética , Síndrome Nefrótico/genética , Osteocondrodisplasias/genética , Embolia Pulmonar/genética , Receptores de Interleucina-7/genética , Linfocitos T/metabolismo , Adolescente , Adulto , Arteriosclerosis/metabolismo , Arteriosclerosis/patología , Células Cultivadas , Niño , Preescolar , ADN Helicasas/genética , Metilación de ADN , Citometría de Flujo , Expresión Génica , Humanos , Inmunohistoquímica , Síndromes de Inmunodeficiencia/metabolismo , Síndromes de Inmunodeficiencia/patología , Interleucina-17/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Mutación , Síndrome Nefrótico/metabolismo , Síndrome Nefrótico/patología , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/patología , Enfermedades de Inmunodeficiencia Primaria , Regiones Promotoras Genéticas/genética , Embolia Pulmonar/metabolismo , Embolia Pulmonar/patología , Receptores de Interleucina-7/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
BACKGROUND: The consequences of surgical site infections can be severe and range from short-term delays in discharge from the hospital to life-threatening infections such as mediastinitis. OBJECTIVES: To evaluate the effectiveness of silver-impregnated dressings in decreasing surgical site infections in children after cardiac surgery. METHODS: A randomized, controlled trial was used to compare silver-impregnated dressings (59 participants) with standard dressings (58 participants). The study team supervised all dressing changes after a sternotomy and ensured adherence with the hospital's bundle for reduction of surgical site infections. The ASEPSIS tool was used to evaluate sternal wounds for evidence of infection. RESULTS: The 2 groups had comparable Risk Adjustment for Congenital Heart Surgery scores, age, sex, weight, height, operating room characteristics, and number of chest tubes and/or pacemaker wires. No surgical site infections occurred in any study participant. Infections did occur, however, during the same period, in cardiac surgical patients who were not enrolled in the study. CONCLUSIONS: The evidence did not support the superiority of silver-impregnated dressings for prevention of surgical site infections in children after cardiac surgery. Adherence to a bundle for prevention of surgical site infections may have decreased the incidence of such infections in the study population during the study period.