Anti-KLRC3 (aa 132-240) polyclonal antibody

Our aim was to identify differentially expressed (DE) genes and biological processes that may help predict patient response to biologic agents for rheumatoid arthritis (RA). Using the INMEX (integrative meta-analysis of expression data) software tool, we performed a meta-analysis of publicly available microarray Gene Expression Omnibus (GEO) datasets that examined patient response to biologic therapy for RA. Three GEO datasets, containing 79 responders and 34 non-responders, were included in the metaanalysis. We identified 1,374 genes that were consistently differentially expressed in responders vs. non-responders (651 up-regulated and 723 down-regulated). The upregulated gene with the smallest p value (p=0.000192) was ASCC2 (Activating Signal Cointegrator 1 Complex Subunit 2), and the up-regulated gene with the largest fold change (average log fold change=-0.75869, p=0.000206) was KLRC3 (Killer Cell Lectin-Like Receptor Subfamily C, Member 3). The down-regulated gene with the smallest p value (p=0.000195) was MPL (Myeloproliferative Leukemia Virus Oncogene). Among the 236 GO terms associated with the set of DE genes, the most significantly enriched was "CTP biosynthetic process" (GO:0006241; p=0.000454). Our meta-analysis identified genes that were consistently DE in responders vs. non-responders, as well as biological pathways associated with this set of genes. These results provide insight into the molecular mechanisms underlying responsiveness to biologic therapy for RA.

Genome-wide association studies (GWAS) are a powerful means of identifying genes with disease-associated common variants, but they are not well-suited to detecting genes with disease-associated rare and low-frequency variants. In the current study of Behcet disease (BD), nonsynonymous variants (NSVs) identified by deep exonic resequencing of 10 genes found by GWAS (IL10, IL23R, CCR1, STAT4, KLRK1, KLRC1, KLRC2, KLRC3, KLRC4, and ERAP1) and 11 genes selected for their role in innate immunity (IL1B, IL1R1, IL1RN, NLRP3, MEFV, TNFRSF1A, PSTPIP1, CASP1, PYCARD, NOD2, and TLR4) were evaluated for BD association. A differential distribution of the rare and low-frequency NSVs of a gene in 2,461 BD cases compared with 2,458 controls indicated their collective association with disease. By stringent criteria requiring at least a single burden test with study-wide significance and a corroborating test with at least nominal significance, rare and low-frequency NSVs in one GWAS-identified gene, IL23R (P = 6.9 x 10(-5)), and one gene involved in innate immunity, TLR4 (P = 8.0 x 10(-4)), were associated with BD. In addition, damaging or rare damaging NOD2 variants were nominally significant across all three burden tests applied (P = 0.0063-0.045). Furthermore, carriage of the familial Mediterranean fever gene (MEFV) mutation Met694Val, which is known to cause recessively inherited familial Mediterranean fever, conferred BD risk in the Turkish population (OR, 2.65; P = 1.8 x 10(-12)). The disease-associated NSVs in MEFV and TLR4 implicate innate immune and bacterial sensing mechanisms in BD pathogenesis.