Innate Lymphoid Cells Groups 1 and 3 in the Epithelial Compartment of Functional Human Intestinal Allografts.

We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16 bowel grafts and compared them with 32 biopsies from native intestines. During the first year posttransplantation, grafts exhibited low levels of IELs (percentage of CD103(+) cells) principally due to reduced CD3(+) CD8(+) cells, while CD103(+) CD3(-) cell numbers became significantly higher. Changes in IEL subsets did not correlate with histology results, isolated intestine, or multivisceral transplants, but CD3(-) IELs were significantly higher in patients receiving corticosteroids. Compared with controls, more CD3(-) IELs of the grafts expressed CD56, NKp44, interleukin (IL)-23 receptor, retinoid-related orphan receptor gamma t (RORγt), and CCR6. No difference was observed in granzyme B, and CD3(-) CD127(+) cells were more abundant in native intestines. Ex vivo, and after in vitro activation, CD3(-) IELs in grafts produced significantly more interferon (IFN)-γ and IL-22, and a double IFNγ(+) IL-22(+) population was observed. Epithelial cell-depleted grafts IELs were cytotoxic, whereas this was not observed in controls. In conclusion, different from native intestines, a CD3(-) IEL subset predominates in grafts, showing features of natural killer cells and intraepithelial ILC1 (CD56(+) , NKp44(+) , CCR6(+) , CD127(-) , cytotoxicity, and IFNγ secretion), ILC3 (CD56(+) , NKp44(+) , IL-23R(+) , CCR6(+) , RORγt(+) , and IL-22 secretion), and intermediate ILC1-ILC3 phenotypes (IFNγ(+) IL-22(+) ). Viability of intestinal grafts may depend on the balance among proinflammatory and homeostatic roles of ILC subsets.

Diagnóstico prenatal y nueva mutación en enfermedad granulomatosa crónica ligada al cromosoma X / Prenatal diagnosis and novel mutation in X-linked chronic granulomatous disease

Introducción: La enfermedad granulomatosa crónica (EGC) es una inmunodeficiencia primaria poco frecuente que se produce por la inactivación del complejo enzimático NADPH oxidasa. Estos pacientes presentan la función fagocítica alterada, lo que les hace más susceptibles a padecer infecciones bacterianas y/o fúngicas. Métodos: Se estudió a un niño de 6 años con sospecha de EGC. El estudio funcional de NADPH oxidasa estaba alterado, diagnosticándose de EGC. Simultáneamente, se nos informó del segundo embarazo de la madre y se solicitó consejo genético. Resultados: Se identificó una mutación nueva causante de enfermedad mediante secuenciación directa del gen CYBB (EGC ligada al X) en el paciente afecto. Al mismo tiempo, se hizo el estudio prenatal cuyo resultado fue la identificación de la misma mutación en el feto. Conclusiones: Es necesario hacer el estudio molecular de la EGC para realizar el diagnóstico de certeza de la enfermedad del paciente con el objetivo de ofrecer diagnóstico prenatal y consejo genético en futuros embarazos (AU)

Background: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency caused by the alteration of the enzyme complex NADPH oxidase, which affects the phagocytic function.CGD patients are susceptible to recurrent infections mainly caused by bacteria and/or fungi. Methods: We studied a 6 year-old boy with suspicion of CGD. The diagnosis was confirmed based on the functional study of NADPH oxidase. Simultaneously, the second pregnancy of the mother was reported and genetic counselling was requested. Results: We identified a new disease-causing mutation by direct sequencing of the CYBB gene (X-linked CGD). The prenatal study resulted in the identification of the same mutation in the foetus. Comments: Molecular genetics characterisation of CGD is needed to obtain an accurate diagnosis of the disease and to offer prenatal diagnosis and genetic counselling in future pregnancies (AU)

[Prenatal diagnosis and novel mutation in X-linked chronic granulomatous disease]. / Diagnóstico prenatal y nueva mutación en enfermedad granulomatosa crónica ligada al cromosoma X.

BACKGROUND: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency caused by the alteration of the enzyme complex NADPH oxidase, which affects the phagocytic function. CGD patients are susceptible to recurrent infections mainly caused by bacteria and/or fungi. METHODS: We studied a 6 year-old boy with suspicion of CGD. The diagnosis was confirmed based on the functional study of NADPH oxidase. Simultaneously, the second pregnancy of the mother was reported and genetic counselling was requested. RESULTS: We identified a new disease-causing mutation by direct sequencing of the CYBB gene (X-linked CGD). The prenatal study resulted in the identification of the same mutation in the foetus. COMMENTS: Molecular genetics characterisation of CGD is needed to obtain an accurate diagnosis of the disease and to offer prenatal diagnosis and genetic counselling in future pregnancies.