title: The expression of inflammatory genes is upregulated in peripheral blood of patients with type 1 diabetes.
abstract: OBJECTIVE
  Our previous gene expression microarray studies identified a number of genes differentially expressed in patients with type 1 diabetes (T1D) and islet autoantibody-positive subjects. This study was designed to validate these gene expression changes in T1D patients and to identify gene expression changes in diabetes complications. RESEARCH DESIGH AND METHODS: We performed high-throughput real-time RT-PCR to validate gene expression changes in peripheral blood mononuclear cells (PBMCs) from a large sample set of 928 T1D patients and 922 control subjects.
  
  
  RESULTS
  Of the 18 genes analyzed here, eight genes (S100A8, S100A9, MNDA, SELL, TGFB1, PSMB3, CD74, and IL12A) had higher expression and three genes (GNLY, PSMA4, and SMAD7) had lower expression in T1D patients compared with control subjects, indicating that genes involved in inflammation, immune regulation, and antigen processing and presentation are significantly altered in PBMCs from T1D patients. Furthermore, one adhesion molecule (SELL) and three inflammatory genes mainly expressed by myeloid cells (S100A8, S100A9, and MNDA) were significantly higher in T1D patients with complications (odds ratio [OR] 1.3-2.6, adjusted P value = 0.005-10(-8)), especially those patients with neuropathy (OR 4.8-7.9, adjusted P value <0.005).
  
  
  CONCLUSIONS
  These findings suggest that inflammatory mediators secreted mainly by myeloid cells are implicated in T1D and its complications.
authors: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, USA.
authors: Yulan
authors: Y
authors: Jin
authors: Ashok
authors: A
authors: Sharma
authors: Colleen
authors: C
authors: Carey
authors: Diane
authors: D
authors: Hopkins
authors: Xiaoxiao
authors: X
authors: Wang
authors: David G
authors: DG
authors: Robertson
authors: Bruce
authors: B
authors: Bode
authors: Stephen W
authors: SW
authors: Anderson
authors: John Chip
authors: JC
authors: Reed
authors: R Dennis
authors: RD
authors: Steed
authors: Leigh
authors: L
authors: Steed
authors: Jin-Xiong
authors: JX
authors: She
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D040501:Calgranulin A / Q000235:genetics; D040502:Calgranulin B / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000235:genetics; D019041:L-Selectin / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology; D055815:Young Adult
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D015214:Antigens, Differentiation, Myelomonocytic; D040501:Calgranulin A; D040502:Calgranulin B; D000949:Histocompatibility Antigens Class II; C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; C075373:MNDA protein, human; C546935:SELL protein, human; C508960:TGFB1 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C045084:invariant chain; D019041:L-Selectin
references: Immunity. 2006 Feb;24(2):179-89
references: 16473830
references: Diabetes. 2007 Nov;56(11):2790-6
references: 17686944
references: J Autoimmun. 2000 Feb;14(1):23-42
references: 10648114
references: Mol Cell Proteomics. 2011 Nov;10(11):M111.012203
references: 21900154
references: Clin Immunol. 2011 Jun;139(3):290-301
references: 21414848
references: J Immunol. 2002 Mar 15;168(6):2659-66
references: 11884430
references: BMC Med Genomics. 2009 Aug 05;2:49
references: 19656400
references: Br Med Bull. 2010;94:145-64
references: 20053672
references: Immunology. 2000 Feb;99(2):320-5
references: 10692053
references: Diabetes. 2004 Aug;53(8):1979-86
references: 15277376
references: Nephron Physiol. 2007;106(2):p26-31
references: 17570945
references: Nat Immunol. 2008 Jun;9(6):632-40
references: 18438410
references: Clin Hemorheol Microcirc. 2009;42(4):285-95
references: 19628894
references: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references: 12184808
references: Int J Immunogenet. 2009 Feb;36(1):47-57
references: 19207936
references: Acta Biochim Biophys Sin (Shanghai). 2009 Apr;41(4):263-72
references: 19352540
references: Cardiovasc Diabetol. 2006 Mar 30;5:6
references: 16573830
references: Am J Respir Crit Care Med. 2010 Aug 1;182(3):341-50
references: 20395555
references: Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10494-8
references: 7504266
references: Clin Exp Immunol. 2005 Sep;141(3):509-17
references: 16045741
references: J Exp Med. 2002 Jun 3;195(11):1499-505
references: 12045248
references: Nat Immunol. 2008 Dec;9(12):1347-55
references: 18997793
references: Eur J Immunol. 1995 Jun;25(6):1502-7
references: 7542194
references: Perit Dial Int. 2007 Sep-Oct;27(5):523-5
references: 17704440
references: Vascul Pharmacol. 2006 Nov;45(5):258-67
references: 17030152
references: Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw. 2005;11(3):147-52
references: 16232368
references: BMC Bioinformatics. 2010 May 14;11:253
references: 20470420
references: Endocrine. 2012 Jun;41(3):430-4
references: 22180056
references: Immunity. 2000 Feb;12(2):171-81
references: 10714683
references: Cardiovasc Diabetol. 2009 Feb 20;8:10
references: 19232095
references: Ann N Y Acad Sci. 2008 Dec;1150:282-9
references: 19120314
references: J Pediatr Endocrinol Metab. 2000 Jan;13(1):85-9
references: 10689642
references: Diabetes. 2008 Oct;57(10):2768-73
references: 18599519
references: Diabetes Care. 2004 Nov;27(11):2769-70
references: 15505025
references: J Clin Endocrinol Metab. 2007 Sep;92(9):3705-11
references: 17595242
references: J Clin Immunol. 2008 Nov;28(6):619-24
references: 18841451
references: Blood. 2005 Apr 1;105(7):2955-62
references: 15598812