title: Distinct monocyte gene-expression profiles in autoimmune diabetes.
abstract: OBJECTIVE
  There is evidence that monocytes of patients with type 1 diabetes show proinflammatory activation and disturbed migration/adhesion, but the evidence is inconsistent. Our hypothesis is that monocytes are distinctly activated/disturbed in different subforms of autoimmune diabetes.
  
  
  METHODS
  We studied patterns of inflammatory gene expression in monocytes of patients with type 1 diabetes (juvenile onset, n = 30; adult onset, n = 30) and latent autoimmune diabetes of the adult (LADA) (n = 30) (controls subjects, n = 49; type 2 diabetic patients, n = 30) using quantitative PCR. We tested 25 selected genes: 12 genes detected in a prestudy via whole-genome analyses plus an additional 13 genes identified as part of a monocyte inflammatory signature previously reported.
  
  
  RESULTS
  We identified two distinct monocyte gene expression clusters in autoimmune diabetes. One cluster (comprising 12 proinflammatory cytokine/compound genes with a putative key gene PDE4B) was detected in 60% of LADA and 28% of adult-onset type 1 diabetic patients but in only 10% of juvenile-onset type 1 diabetic patients. A second cluster (comprising 10 chemotaxis, adhesion, motility, and metabolism genes) was detected in 43% of juvenile-onset type 1 diabetic and 33% of LADA patients but in only 9% of adult-onset type 1 diabetic patients.
  
  
  CONCLUSIONS
  Subgroups of type 1 diabetic patients show an abnormal monocyte gene expression with two profiles, supporting a concept of heterogeneity in the pathogenesis of autoimmune diabetes only partly overlapping with the presently known diagnostic categories.
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Roos C
authors.initials: RC
authors.lastname: Padmos
authors.forename: Nanette C
authors.initials: NC
authors.lastname: Schloot
authors.forename: Huriya
authors.initials: H
authors.lastname: Beyan
authors.forename: Cindy
authors.initials: C
authors.lastname: Ruwhof
authors.forename: Frank J T
authors.initials: FJ
authors.lastname: Staal
authors.forename: Dick
authors.initials: D
authors.lastname: de Ridder
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Aanstoot
authors.forename: Wai Kwan
authors.initials: WK
authors.lastname: Lam-Tse
authors.forename: Harm
authors.initials: H
authors.lastname: de Wit
authors.forename: Christian
authors.initials: C
authors.lastname: de Herder
authors.forename: Roos C
authors.initials: RC
authors.lastname: Drexhage
authors.forename: Barbara
authors.initials: B
authors.lastname: Menart
authors.forename: R David
authors.initials: RD
authors.lastname: Leslie
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D002648:Child; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D016207:Cytokines; D000683:Serum Amyloid P-Component; D000099153:Pentraxins