Human NFKBIB ELISA Matched Antibody Pair

Background. Epigenetic mechanisms may be important in the progression of chronic kidney disease (CKD). Methods. We studied the genome-wide DNA methylation pattern associated with rapid loss of kidney function using the Infinium Human Methylation 450 K BeadChip in 40 Chronic Renal Insufficiency (CRIC) study participants (n = 3939) with the highest and lowest rates of decline in estimated glomerular filtration rate. Results. The mean eGFR slope was 2.2 (1.4) and -5.1 (1.2) mL/min/1.73 m(2) in the stable kidney function group and the rapid progression group, respectively. CpG islands in NPHP4, IQSEC1 and TCF3 were hypermethylated to a larger extent in subjects with stable kidney function (P-values of 7.8E-05 to 9.5E-05). These genes are involved in pathways known to promote the epithelial to mesenchymal transition and renal fibrosis. Other CKD-related genes that were differentially methylated are NOS3, NFKBIL2, CLU, NFKBIB, TGFB3 and TGFBI, which are involved in oxidative stress and inflammatory pathways (P-values of 4.5E-03 to 0.046). Pathway analysis using Ingenuity Pathway Analysis showed that gene networks related to cell signaling, carbohydrate metabolism and human behavior are epigenetically regulated in CKD. Conclusions. Epigenetic modifications may be important in determining the rate of loss of kidney function in patients with established CKD.

Transforming growth factor beta 1 (TGFB1) likely contributes to the pathogenesis of Epstein-Barr virus (EBV)-mediated cancer. A microarray containing 59 probes for detecting mRNA of members of TGFB1-associated pathways was developed. mRNA expression of TGFB1 receptors and members of connected pathways were examined in peripheral blood leukocytes of patients during acute EBV infection and after recovery. TGFB1 and TGFBR2 mRNA expression was increased in patients with EBV infection. Similarly, mRNA expression of protein kinase C (PRKCB), MAP3K7, PDLIM7, and other members of TGFB1 and NF-kappa B signaling pathways increased. A shift of mRNA transcript variant expression of some key members (TGFBR2, PRKCB, and NFKBIB) of involved signaling pathways was detected. After the patients' recovery, most of the altered mRNA expression has been normalized. We speculate that in patients with EBV infection, members of TGFB1-associated pathways contribute to the suppression of proapoptotic and induction of pro-survival factors in leukocytes. The modulation of TGFB1-associated pathways may be considered as a potential risk factor in the development of EBV-associated tumors in patients with acute EBV infection.