Rotavirus in India: Forty years of research

Rotavirus was first identified as a human pathogen just over 40 years ago, and work on this pathogen in India started shortly thereafter. Subsequent studies have confirmed its pre-eminent role in gastroenteritis in children in India. Standardized surveillance has enabled the documentation of the high burden of disease, and has demonstrated that there is considerable geographic and temporal variation in strain circulation. Internationally licensed vaccines, vaccine candidates based on indigenous strains and out-licensed strains have been tested for safety, immunogenicity and efficacy; three vaccines are now licensed in India and are used in the private sector. Public sector vaccination has begun, and it will be path-breaking for Indian vaccinologists to measure impact of vaccine introduction in terms of safety and effectiveness. So far, India has kept pace with international epidemiologic and vaccine research on rotavirus, and these efforts should continue.     

Deletion of Lkb1 in Renal Tubular Epithelial Cells Leads to CKD by Altering Metabolism

Renal tubule epithelial cells are high-energy demanding polarized epithelial cells. Liver kinase B1 (LKB1) is a key regulator of polarity, proliferation, and cell metabolism in epithelial cells, but the function of LKB1 in the kidney is unclear. Our unbiased gene expression studies of human control and CKD kidney samples identified lower expression of LKB1 and regulatory proteins in CKD. Mice with distal tubule epithelial-specific Lkb1 deletion (Ksp-Cre/Lkb1^flox/flox) exhibited progressive kidney disease characterized by flattened dedifferentiated tubule epithelial cells, interstitial matrix accumulation, and dilated cystic-appearing tubules. Expression of epithelial polarity markers β-catenin and E-cadherin was not altered even at later stages. However, expression levels of key regulators of metabolism, AMP-activated protein kinase (Ampk), peroxisome proliferative activated receptor gamma coactivator 1-α (Ppargc1a), and Ppara, were significantly lower than those in controls and correlated with fibrosis development. Loss of Lkb1 in cultured epithelial cells resulted in energy depletion, apoptosis, less fatty acid oxidation and glycolysis, and a profibrotic phenotype. Treatment of Lkb1-deficient cells with an AMP-activated protein kinase (AMPK) agonist (A769662) or a peroxisome proliferative activated receptor alpha agonist (fenofibrate) restored the fatty oxidation defect and reduced apoptosis. In conclusion, we show that loss of LKB1 in renal tubular epithelial cells has an important role in kidney disease development by influencing intracellular metabolism.     

The Interaction Between Prenatal Exposure to Home Renovation and Reactive Oxygen Species Genes in Cord Blood IgE Response is Modified by Maternal Atopy

Purpose

Although home renovation exposure during childhood has been identified as a risk factor for the development of allergy, there is limited information on the association between prenatal exposure to home renovation and cord blood (CB) IgE response. The aims of this study were to identify the effect of prenatal exposure to home renovation on CB IgE levels, and to investigate whether this exposure interacts with neonatal genes and whether the effect can be modified by maternal atopy.

Methods

This study included 1,002 mother-neonate pairs from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). Prenatal environmental factors were collected using a questionnaire. The levels of CB IgE were measured by the ImmunoCAP system, and DNA was extracted from CB.

Results

Exposure to home renovation during the prenatal period was associated with significantly higher levels of CB IgE only in neonates from atopic mothers, and the effect of renovation exposure on CB IgE levels persisted from 31 months before birth. Furthermore, prenatal exposure to home renovation increased the risk of CB IgE response interacting with polymorphisms of NRF2 and GSTP1 genes only in neonates from atopic mothers.

Conclusions

Maternal atopy modified the effect of prenatal exposure to home renovation on CB serum IgE response as well as the interaction between the exposure and neonatal genes involved in the oxidative stress pathway. These findings suggest that the genetically susceptible offspring of atopic mothers may be more vulnerable to the effect of prenatal exposure to home renovation on the development of allergy.