DISTINCT MONOCYTE GENE-EXPRESSION PROFILES IN Autoimmune DIABETES

Abstract

Objective: There is evidence that monocytes of patients with type 1 diabetes (T1D) show pro-inflammatory activation and disturbed migration/adhesion, but the evidence is inconsistent. Our hypothesis is that monocytes are distinctly activated/disturbed in different sub forms of autoimmune diabetes.

Research Design and Methods: We studied patterns of inflammatory gene expression in monocytes of patients with T1D (juvenile, n=30, and adult, n=30, onset) and latent autoimmune diabetes of the adult (LADA) (n=30) (controls: healthy subjects, n=49, type 2 diabetes patients, n=30) using quantitative-PCR (Q-PCR). We tested 25 selected genes: 12 genes detected in a pre-study 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 pro-inflammatory cytokine/compound genes with a putative key gene PDE4B) was detected in LADA (60%) and adult-onset T1D (28%), but in only 10% juvenile-onset T1D. A second cluster (comprising 10 chemotaxis, adhesion, motility and metabolism genes) was detected in juvenile-onset T1D (43%) and LADA (33%) but in only 9% adult-onset T1D.

Conclusions: Sub-groups of T1D patients show an abnormal monocyte gene expression with two profiles, supporting a concept of heterogeneity in the pathogenesis of immune-mediated diabetes only partly overlapping with the presently known diagnostic categories.