Dissecting the localization of lipopolysaccharide-responsive and beige-like anchor protein (LRBA) in the endomembrane system

Introduction and objectives: LRBA deficiency is caused by loss of LRBA protein expression, due to either homozygous or compounds heterozygous mutations in LRBA. LRBA deficiency has been shown to affect vesicular trafficking and autophagy. To date, LRBA has been observed in the cytosol, Golgi apparatus and some lysosomes in LPS-stimulated murine macrophages. The objectives of the present study were to study the LRBA localization in organelles involved in vesicular traffic, phagocytosis, and autophagy in mononuclear phagocytes (MP). Materials and methods: We analyzed LRBA colocalization with different endosomes markets using confocal microscopy in MP. We used the autophagy inhibitors to determine the role of LRBA in formation, maturation or degradation of the autophagosome. Results: LRBA intracellular trafficking depends on the activity of the GTPase ADP ribosylation factor-1 (ARF) in MP. LRBA was identified in early, late endosomes but did not colocalize strongly with lysosomal markers. Although LRBA appears not to be recruited during the phagocytic cargo uptake, it greatly colocalized with the microtubule-associated protein 1A/1B-light chain 3 (LC3) under a steady state and this decreased after the induction of autophagy flux. Although the use of inhibitors of lysosome fusion did not restore the LRBA/LC3 colocalization, inhibitors of either early to late endosomes trafficking or PI3K pathway did. Conclusions: Taken together, our results show that LRBA is located in endomembrane system vesicles, mainly in the early and late endosomes. Although LRBA appears not to be involved in the phagocytic uptake, it is recruited in the early steps of the autophagy flux

No disponible

Diagnòstic diferencial de la icterícia en el lactant / No disponible

No disponible

Primary immunodeficiency diseases in Northern Iran

INTRODUCTION: Primary immunodeficiency diseases (PID) are a heterogeneous group of inherited disorders, characterised by recurrent severe infections, autoimmunity and lymphoproliferation. Despite impressive progress in identification of novel PID, there is an unfortunate lack of awareness among physicians in identification of patients with PID, especially in non-capital cities of countries worldwide. RESULT: This study was performed in a single-centre paediatric hospital in Northern Iran during a 21-year period (1994-2015). Ninety-four patients were included in this study. The majority of cases had antibody deficiencies (37.23%), followed by well-defined syndromes with immunodeficiency in 16 (17.02%), phagocytic disorders in 15 patients (15.95%), complement deficiencies in 15 patients (15.95%), immunodeficiencies affecting cellular and humoral immunity in nine patients (9.57%), disease of immune dysregulation in three (3.19%), and defects in intrinsic and innate immunity in one (1.06%). CONCLUSION: It seems that there are major variations in frequency of different types of PID in different regions of a country. Therefore, reporting local data could provide better ideas to improve the local health care system strategists and quality of care of PID patients

No disponible

Liquen plano oral y dendrocitos dérmicos / Oral lichen Planus and Dermal Dendrocytes

Introducción: El liquen plano oral (LPO) es una enfermedad inflamatoria relativamente frecuente que se presenta con un amplio abanico de formas clínicas. Todavía no se ha determinado completamente su patogenia, aunque se sabe que los linfocitos actúan de mediadores con la participación de citoquinas y otras células inflamatorias, entre ellas los dendrocitos dérmicos (DD) tipo I y tipo II (DD positivos para el factor XIIIA y CD34, respectivamente).Objetivos. Describir la presencia y distribución de estas células en el tejido, mediante técnicas inmunohistoquímicas, en 23 muestras procedentes de pacientes que reunían los criterios clínicos e histopatológicos de LPO. Resultados: Los DD factor XIII+ estaban localizados principalmente en la dermis superficial (p < 0,0001) y no en la submucosa profunda. Dichas células se encontraban en abundancia en toda la unión dermoepidérmica y se relacionaban estrechamente con la infiltración linfocitaria. Los DD factor XIIIa+ se encontraban además en el epitelio y la dermis profunda. En cambio, los DD CD34+ se distribuyeron principalmente en la dermis profunda, directamente por debajo del infiltrado linfocitario, con pocas células en la zona subepitelial. Conclusiones: Los DD estaban presentes en el LPO, con diferentes distribuciones en los tejidos. Así, los DD factor XIIIa+ predominaban en la dermis superficial, mientras que los DD CD34+ se encontraban principalmente en la dermis profunda. Esto apunta a que los DD, y sobre todo los DD factor XIIIa+ debido a su capacidad para expresar moléculas de adhesión intercelulares-1 (ICAM-1) y el factor de necrosis tumoral alfa (TNF-α), pueden desempeñar una función destacada en la patogénesis del LPO (AU)

Introduction: Oral lichen planus (OLP) is a relatively common inflammatory disease with a wide range of clinical forms. Its pathogenesis has not been fully elucidated although it is known to be mediated by lymphocytes with the participation of cytokines and other inflammatory cells, including type I and type II dermal dendrocytes (DD) (factor xiIIa+ DD and CD34+ DD, respectively). Objectives: To describe the presence and tissue distribution of these cells, through immunohistochemistry, in 23 specimens from patients with clinical and histopathological criteria of OLP. Results: Factor xiIIa+ DD were mainly located in the superficial dermis (p < 0.0001) as opposed to the deep submucosa. These cells were abundant throughout the dermal-epidermal junction and closely related to lymphocyte infiltration. Moreover, factor xiIIa+ DD were also found in the epithelium and deep dermis. CD34+ DD were distributed mostly to the deep dermis directly below the lymphocyte infiltrate with few cells in the subepithelial region. Conclusions: DD were present in OLP, with distinct tissue distributions. Factor xiIIa+ DD were predominant in the superficial dermis while CD34+ DD could be found mostly in the deep dermis. These findings suggest that DD, and those positive for factor xiIIa+ in particular in view of their ability to express intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor α (TNF-α), may play an important role in pathogenesis of OLP (AU)

Infección congénita por citomegalovirus y displasia cortical difusa / Congenital cytomegalovirus infection and diffuse cortical dysplasia

Introducción: La infección congénita por citomegalovirus(CMV) es la infección vírica más frecuente transmitida de forma intra uterina que afecta al sistema nervioso central (SNC), con un amplio espectro de alteraciones, incluidos los trastornos del desarrollo cortical, en especial la polimicrogiria, aunque cualquier displasia cortical es posible. Caso clínico: Niña de 4 años y 2 meses, con infección congénita por CMV diagnosticada en el periodo neonatal por hepatosplenomegalia que presenta retraso psicomotor global, tetraparesia espástica y microcefalia. La tomografía axial computarizada evidencia displasia cortical difusa sin otras alteraciones. Discusión: El CMV es el agente infeccioso más implicado en las malformaciones del desarrollo cortical y debe considerarse en su investigación etiológica. El riesgo de repetición en siguientes embarazos es menor que en los trastornos de la migración neuronal de causa genética, como enfermedades peroxisomales o agiria-paquigiria hereditaria

Introduction: Congenital cytomegalovirus(CMV) infection is the most common viral disease known to be transmitted in utero and to affect the central nervous system. It is associated with a wide spectrum of abnormalities, including disorders of cortical development, especially polymicrogyria, although any type of cortical dysplasia can be involved. Case report: The authors report the case of a 4-year 2-month-old girl with congenital CMV infection diagnosed at the neonatal period by hepatosplenomegaly, with a global developmental delay, spastic tetraparesia and microcephaly. Cranial CT showed diffuse cortical dysplasia without other abnormalities. Discussion: CMV is the most common infectious agent involved in disorders of cortical development and has to be considered in the investigation of the etiology. The risk of repetition is lower than for other causes of disorder of neuronal migrationas genetic disease like peroxisomal disorders and hereditary agyria/pachygyria