Epigenetic Markers of B-Cell Function in Low Birth Weight Infants

Low birth weight (LBW) status (< 10% for gestational age at birth) is associated with
increased risk for diseases such as type II diabetes mellitus, hypertension, chronic
obstructive pulmonary disease and coronary artery disease in adults, and represents one
example of the "fetal onset of adult disease" hypothesis. Recent data strongly associates
LBW status with impaired innate and adaptive immunity leading to increased risk for severe
infections during adolescence or early adulthood. Animal studies suggest that the ratio of
certain B lymphocyte subpopulations, the B1a and B1b cells, determines whether deficits in
immunity occur.

This study will determine the ratio of B1b to B1a lymphocyte subpopulations in the cord
blood of infants born LBW in the late preterm to term gestations (> 34 weeks at birth) and
compare those ratios with those of normal birth weight (NBW) controls in a nested case
control study design.

Furthermore, animal studies suggest that the expression patterns of CD5 and CD19 proteins
determines the cellular phenotype of the B lymphocyte, that of a B1a or a B1b cell, and that
the regulatory regions controlling their expression are epigenetically vulnerable. The
investigators will therefore isolate DNA and RNA from both B lymphocyte subpopulations and
determine whether epigenetic changes to the regulatory regions of the genes coding for CD5
and CD19 protein expression occur in LBW lymphocyte subpopulations as compared to the
lymphocytes from NBW infants.

This proposal will be the first human study to examine epigenetic determination of a
maladaptive phenotype following LBW status at birth in a specific cell type leading to a
specific impairment of innate and adaptive immunity.