The Short-Stature Homeobox-Containing Gene (shox/SHOX) Is Required for the Regulation of Cell Proliferation and Bone Differentiation in Zebrafish Embryo and Human Mesenchymal Stem Cells.

The short-stature homeobox-containing gene (SHOX) was originally discovered as one of genes responsible for idiopathic short-stature syndromes in humans. Previous studies in animal models have shown the evolutionarily conserved link between this gene and skeletal formation in early embryogenesis. Here, we characterized developmental roles of shox/SHOX in zebrafish embryos and human mesenchymal stem cells (hMSCs) using loss-of-function approaches. Morpholino oligo-mediated knockdown of zebrafish shox markedly hindered cell proliferation in the anterior region of the pharyngula embryos, which was accompanied by reduction in the dlx2 expression at mesenchymal core sites for future pharyngeal bones. In addition, the impaired shox expression transiently increased expression levels of skeletal differentiation genes in early larval stage. In cell culture studies, we found that hMSCs expressed SHOX; the siRNA-mediated blockade of SHOX expression significantly blunted cell proliferation in undifferentiated hMSCs but the loss of SHOX expression did augment the expressions of subsets of early osteogenic genes during early osteoblast differentiation. These data suggest that shox/SHOX maintains the population of embryonic bone progenitor cells by keeping its proliferative status and by repressing the onset of early osteogenic gene expression. The current study for the first time shows cellular and developmental responses caused by shox/SHOX deficiency in zebrafish embryos and hMSCs, and it expands our understanding of the role of this gene in early stages of skeletal growth.

Eosinophilic gastroenteritis in a patient with Bruton's tyrosine kinase deficiency.

Eosinophilic gastrointestinal diseases (EGID) are relatively rare diseases characterized by eosinophilic infiltration of the gastrointestinal tract resulting in various gastrointestinal symptoms. EGID are often caused by allergic reactions or systemic eosinophilic disorders, but their comorbidity with Bruton's tyrosine kinase (BTK) deficiency has not been previously documented. Here, we report a case of eosinophilic gastroenteritis (EG) in a patient with BTK deficiency. Despite adequate replacement immunoglobulin (Ig) therapy, trough serum IgG was not maintained. To identify the underlying cause of the low trough level and chronic diarrhea, the intestine was investigated on endoscopy. We also screened for the variable number of tandem repeat polymorphism in FCGRT. Genetic analysis could not explain the low trough IgG, but endoscopy indicated eosinophilic enterocolitis. EG may be an important differential diagnosis when primary immunodeficiency patients have chronic diarrhea or continued low serum IgG.

Management of tacrolimus-associated food allergy after liver transplantation.

Increasingly, food allergy associated with tacrolimus after pediatric living-donor liver transplantation (LT) has been reported. Tacrolimus prevents the activation of T cells by blocking calcineurin, thus producing an immunosuppressive effect, but tacrolimus induces an imbalance in T-helper type 1 (Th1) and Th2 cells in the food allergy process. This report describes a case of tacrolimus-associated food allergy after pediatric living-donor LT. The patient was a 7-year-old Japanese girl who had undergone living-donor LT at 12 months of age, and whom we first saw in the clinic at age 18 months. She received immunosuppressive therapy by tacrolimus after transplantation. Atopic dermatitis developed in post-transplant month 18. Stridor, facial edema, lip swelling, and skin erythema after consuming tempura udon containing wheat occurred in post-transplant month 39, and she was subsequently diagnosed with anaphylactic shock. Eosinophilic leukocyte and serum immunoglobulin (Ig)E increased, and specific IgE was positive for some food allergens. Pharmacotherapy was therefore changed from tacrolimus to cyclosporine A, after which eosinophilic leukocyte and serum IgE decreased and atopic dermatitis improved.