STANDARD_NAME GSE9006_1MONTH_VS_4MONTH_POST_TYPE_1_DIABETES_DX_PBMC_UP SYSTEMATIC_NAME M5790 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE9006_1MONTH_VS_4MONTH_POST_TYPE_1_DIABETES_DX_PBMC_UP NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes up-regulated in comparison of peripheral blood mononuclear cells (PBMC) from patients with type 1 diabetes at 1 month after the diagnosis versus those at 4 months later. DESCRIPTION_FULL Objective: We hypothesized that type 1 diabetes (T1D) is accompanied by changes in gene expression in peripheral blood mononuclear cells (PBMCs) due to dysregulation of adaptive and innate immunity, counterregulatory responses to immune dysregulation, insulin deficiency and hyperglycemia. Research Design and Methods: Microarray analysis was performed on PBMCs from 43 patients with newly diagnosed T1D, 12 patients with newly diagnosed type 2 diabetes (T2D) and 24 healthy controls. One and four month follow-up samples were obtained from 20 of the T1D patients. Results: Microarray analysis identified 282 genes differing in expression between newlydiagnosed T1D patients and controls at a false discovery rate of 0.05. Changes in expression of interleukin-1β (IL1B), early growth response gene 3 (EGR3), and prostaglandin-endoperoxide synthase 2 (PTGS2) resolved within four months of insulin therapy and were also observed in T2D suggesting that they resulted from hyperglycemia. With use of a knowledge base, 81/282 genes could be placed within a network of interrelated genes with predicted functions including apoptosis and cell proliferation. IL1B and the MYC oncogene were the most highly-connected genes in the network. IL1B was highly overexpressed in both T1D and T2D, whereas MYC was dysregulated only in T1D. Conclusion: T1D and T2D likely share a final common pathway for beta cell dysfunction that includes secretion of interleukin-1β and prostaglandins by immune effector cells, exacerbating existing beta cell dysfunction, and causing further hyperglycemia. The results identify several targets for disease-modifying therapy of diabetes and potential biomarkers for monitoring treatment efficacy. PMID 17595242 GEOID GSE9006 AUTHORS Kaizer EC,Glaser CL,Chaussabel D,Banchereau J,Pascual V,White PC CONTRIBUTOR Jernej Godec CONTRIBUTOR_ORG Dana-Farber Cancer Institute EXACT_SOURCE GSE9006_2243_200_UP FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AATF,ABCB11,ACOT9,ADCK2,ADM,AEN,ALOX5,ANXA3,AQP9,ARHGAP26,ARHGEF16,ASPM,ATF4,ATG2A,B3GNT4,BCL2A1,BCL6,BMP2,C10orf57,C17orf91,C6orf123,CAMK2N1,CAPN3,CARS2,CBX6,CCDC90A,CCNJ,CD2BP2,CD83,CEACAM8,CHAF1A,COL8A2,COX16,CPPED1,CREM,CRYBG3,CTAGE1,CTRL,CTSZ,CXCL1,CYP3A7,DEFB1,DHCR24,DIP2A,DKFZp547G183,DLX6,DNAJC1,DNAJC2,DOCK2,DOCK5,EFCAB11,EGLN3,EMILIN2,ENC1,EYA1,FAM13A,FAM46A,FAM70A,FIG4,FLRT3,FPR1,FUT4,GCNT4,GMDS,GNAQ,GNG10,GNG12,GPC5,GPR12,GPR124,GPR137B,GRAMD1B,GRAMD4,GUCY1A3,HERC2P3,HIC2,HK3,HLX,ICAM4,IER3,IFI30,IFIT3,IL1R2,IL33,IMPDH1,INPP5A,IRF1,KAZALD1,KBTBD11,KIAA0232,KIR3DX1,KITLG,KLF4,KLHL36,KPTN,LDLR,LETM1,LIN7A,LOC100130331,LOC100286937,LOC441204,LPPR4,LRRFIP2,LUM,MAF,MAFF,MAGEB3,MGAM,MME,MMP8,MNT,MOSC2,MRAS,MTF1,MUC7,MYBBP1A,MYL5,NAA11,NADSYN1,NAMPT,NFKBIA,NFKBIE,NID2,NLRP3,NOC2L,NPC2,NUFIP1,NUP93,OBSL1,OR3A1,OR7E24,P2RY2,PABPC1,PCSK1,PDCD1LG2,PIGT,PIM1,PIWIL1,PLXNC1,PRKD1,PTP4A1,PTX3,PVRL3,PYGL,R3HCC1,RAP2C,RASSF9,RBMS1,RFX4,RPL37A,RXRA,S100P,SAT1,SCCPDH,SCD5,SCO2,SERPINA1,SGK1,SLC19A1,SLC22A4,SLC30A9,SLC39A9,SMURF1,SNORA21,SPRED2,SPTLC2,SRGAP2,STX4,SUSD5,SYCP1,TALDO1,TAS2R4,TAX1BP3,TBC1D17,TCIRG1,TEX2,TFRC,TIAL1,TLR1,TNF,TNFAIP6,TNFRSF8,TNNI2,TPMT,TRDN,TRIB1,TRIL,TRIM29,TSPAN9,TULP2,TYR,UPP1,USP13,VNN2,WWP2,ZAK,ZBP1,ZNF280B,ZNF287,ZNF394 GENE_SYMBOLS AATF,ABCB11,ACOT9,ADCK2,ADM,AEN,ALOX5,ANXA3,AQP9,ARHGAP26,ARHGEF16,ASPM,ATF4,ATG2A,B3GNT4,BCL2A1,BCL6,BMP2,TMEM254,MIR22HG,LINC01558,CAMK2N1,CAPN3,CARS2,CBX6,MCUR1,CCNJ,CD2BP2,CD83,CEACAM8,CHAF1A,COL8A2,COX16,CPPED1,CREM,CRYBG3,CTAGE1,CTRL,CTSZ,CXCL1,CYP3A7,DEFB1,DHCR24,DIP2A,,DLX6,DNAJC1,DNAJC2,DOCK2,DOCK5,EFCAB11,EGLN3,EMILIN2,ENC1,EYA1,FAM13A,TENT5A,TMEM255A,FIG4,FLRT3,FPR1,FUT4,GCNT4,GMDS,GNAQ,GNG10,GNG12,GPC5,GPR12,ADGRA2,GPR137B,GRAMD1B,GRAMD4,GUCY1A1,HERC2P3,HIC2,HK3,HLX,ICAM4,IER3,IFI30,IFIT3,IL1R2,IL33,IMPDH1,INPP5A,IRF1,KAZALD1,KBTBD11,KIAA0232,KIR3DX1,KITLG,KLF4,KLHL36,KPTN,LDLR,LETM1,LIN7A,ENSG00000237250,,LINC02981,PLPPR4,LRRFIP2,LUM,MAF,MAFF,MAGEB3,MGAM,MME,MMP8,MNT,MTARC2,MRAS,MTF1,MUC7,MYBBP1A,MYL5,NAA11,NADSYN1,NAMPT,NFKBIA,NFKBIE,NID2,NLRP3,NOC2L,NPC2,NUFIP1,NUP93,OBSL1,OR3A1,OR7E24,P2RY2,PABPC1,PCSK1,PDCD1LG2,PIGT,PIM1,PIWIL1,PLXNC1,PRKD1,PTP4A1,PTX3,NECTIN3,PYGL,R3HCC1,RAP2C,RASSF9,RBMS1,RFX4,RPL37A,RXRA,S100P,SAT1,SCCPDH,SCD5,SCO2,SERPINA1,SGK1,SLC19A1,SLC22A4,SLC30A9,SLC39A9,SMURF1,SNORA21,SPRED2,SPTLC2,SRGAP2,STX4,SUSD5,SYCP1,TALDO1,TAS2R4,TAX1BP3,TBC1D17,TCIRG1,TEX2,TFRC,TIAL1,TLR1,TNF,TNFAIP6,TNFRSF8,TNNI2,TPMT,TRDN,TRIB1,TRIL,TRIM29,TSPAN9,TULP2,TYR,UPP1,USP13,VNN2,WWP2,MAP3K20,ZBP1,ZNF280B,ZNF287,ZNF394 FOUNDER_NAMES