Hemophagocytic lymphohistiocytosis in a child with chronic granulomatous disease: A rare complication of a rare disorder.

Chronic Granulomatous Disease (CGD) is a primary immunodeficiency disorder (PID) of phagocytic cells resulting in failure to eradicate catalase positive microorganisms like Staphylococci and fungal infections; due to deficiency or malfunction of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase subunits in phagocytic leucocytes. We illustrate here one such case; a six year old girl who was admitted in our hospital with history of prolonged fever, non resolving bilateral otitis media and recurrent pneumonia. She was evaluated for an underlying PID and was found to have CGD based on Nitro blue Tetrazolium (NBT) Slide Test and flow cytometric Dihydrorhodamine (DHR) assay. The child was symptomatic despite initial treatment with first-line followed by second-line antibiotics. During the course of current systemic infection, she also developed infection-associated secondary Hemophagocytic Lympho Histiocytosis (HLH) as suggested by her clinical and laboratory parameters. Despite a thorough search, no microorganism could be isolated and so she was treated with empircal antibiotic therapy comprising of meropenem, linezolid and an antifungal. Fever resolved with gradual improvement of laboratory parameters and finally spontaneous resolution of HLH. We conclude that a high index of suspicion for PID is required in a child with recurrent infections. Identification of underlying infectious agent should be attempted to start targeted antimicrobial therapy; both to prevent as well as cure infection associated secondary HLH.

Primary Sjogren's syndrome manifesting with distal renal tubular acidosis and severe metabolic bone disease.

Sjogren's syndrome (SS) is a chronic, autoimmune, inflammatory disorder affecting primarily the salivary and lacrimal glands with potential for systemic involvement. The disease predominantly occurs in women in the age group of 35-45 years and is relatively rare in children. It mainly affects salivary and lacrimal glands with potential for systemic involvement. Children presenting with the severe metabolic bone disease at the very outset has not been reported in the paediatric literature. We report a 13-year-old girl who presented with pain in multiple large joints with predominant involvement of hip joints leading to difficulty in walking for the past 6 months and unintentional weight loss of the same duration. Investigations revealed distal renal tubular acidosis with severe metabolic bone disease as an extra-glandular manifestation of primary SS.

Engraftment of sorted/expanded human central nervous system stem cells from fetal brain.

Direct isolation of human central nervous system stem cells (CNS-SC) based on cell surface markers yields a highly purified stem cell population that can extensively expand in vitro and exhibit multilineage differentiation potential both in vitro and in vivo. The CNS-SC were isolated from fetal brain tissue using the cell surface markers CD133(+), CD34(-), CD45(-), and CD24(-/lo) (CD133(+) cells). Fluorescence-activated cell sorted (FACS) CD133(+) cells continue to expand exponentially as neurospheres while retaining multipotential differentiation capacity for >10 passages. CD133(-), CD34(-), and CD45(-) sorted cells (approximately 95% of total fetal brain tissue) fail to initiate neurospheres. Neurosphere cells transplanted into neonatal immunodeficient NOD-SCID mice proliferated, migrated, and differentiated in a site-specific manner. However, it has been difficult to evaluate human cell engraftment, because many of the available monoclonal antibodies against neural cells (beta-tubulin III and glial fibrillary acidic protein) are not species specific. To trace the progeny of human cells after transplantation, CD133(+)-derived neurosphere cells were transduced with lentiviral vectors containing enhanced green fluorescent protein (eGFP) expressed downstream of the phosphoglycerate kinase promoter. After transduction, GFP(+) cells were enriched by FACS, expanded, and transplanted into the lateral ventricular space of neonatal immunodeficient NOD-SCID brain. The progeny of transplanted cells were detected by either GFP fluorescence or antibody against GFP. GFP(+) cells were present in the subventricular zone-rostral migrating stream, olfactory bulb, and hippocampus as well as nonneurogenic sites, such as cerebellum, cerebral cortex, and striatum. Antibody against GFP revealed that some of the cells displayed differentiating dendrites and processes with neurons or glia cells. Thus, marking human CNS-SC with reporter genes introduced by lentiviral vectors is a useful tool with which to characterize migration and differentiation of human cells in this mouse transplantation model.