Human NFKBIB ELISA Matched Antibody Pair

Rationale: Increasing evidence supports a key role for the transcription factor nuclear factor (NF)-kappa B in the host response to pneumococcal infection. Control of NF-KB activity is achieved through interactions with the I kappa B family of inhibitors, encoded by the genes NFKBIA, NFKBIB, and NFKBIE. Rare NFKBIA mutations cause immunodeficiency with severe bacterial infection, raising the possibility that common I kappa B gene polymorphisms confer susceptibility to common bacterial disease. Objectives: To determine whether polymorphisms in NFKBIA, NFKBIB, and NFKBIE associate with susceptibility to invasive pneumococcal disease (IPD) and thoracic empyema. Methods: We studied the frequencies of 62 single-nucleotide polymorphisms (SNPs) across NFKBIA, NFKBIB, and NFKBIE in individuals with IPD and control subjects (n = 1,060). Significantly associated SNPs were then studied in a group of individuals with thoracic empyema and a second control group (n = 632). Measurements and Main Results: Two SNPs in the NFKBIA promoter region were associated with protection from IPD in both the initial study group and the pneumococcal empyema subgroup. Significant protection from IPD was observed for carriage of mutant alleles at these two loci on combining the groups (SNP rs3138053: Mantel-Haenszel 2 x 2 chi(2) = 13.030, p = 0.0003; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.45-0.79; rs2233406: Mantel-Haenszel 2 x 2 chi(2) = 18.927, p = 0.00001; OR, 0.55; 95% CI, 0.42-0.72). An NFKBIE SNP associated with susceptibility to IPD but not pneumococcal empyema. None of the NFKBIB SNPs associated with IPD susceptibility. Conclusions: NFKBIA polymorphisms associate with susceptibility to IPD. Genetic variation in an inhibitor of NF-KB therefore not only causes a very rare immunodeficiency state but may also influence the development of common infectious disease.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects "1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor a, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis. In total, 25 single nucleotide polymorphisms were found to be associated with anti-TNF treatment response in RA (19 from genome-wide association studies and 6 from the meta-analyses), and these map to genes involved in T cell function, NFKB and TNF signalling pathways (including CTCN5, TEC, PTPRC, FCGR2A, NFKBIB, FCGR2A, IRAK3). Explorative prediction analyses found that biomarkers for clinical treatment selection are not yet available.