Distinct Monocyte Gene-Expression Profiles in Autoimmune Diabetes

Distinct Monocyte Gene-Expression Profiles in Autoimmune Diabetes Roos C. Padmos 1 , Nanette C. Schloot 2 , Huriya Beyan 3 , Cindy Ruwhof 1 , Frank J.T. Staal 1 , Dick de Ridder 4 , Henk-Jan Aanstoot 1 , Wai Kwan Lam-Tse 1 , Harm de Wit 1 , Christian de Herder 2 , Roos C. Drexhage 1 , Barbara Menart 2 , R. David Leslie 3 , Hemmo A. Drexhage 1 and the LADA Consortium * 1 Department of Immunology, Erasmus MC, Rotterdam, the Netherlands 2 German Diabetes Center, Düsseldorf, Germany 3 St. Bartholomew's Hospital, London, U.K 4 Delft University of Technology, Delft, the Netherlands Corresponding author: Hemmo A. Drexhage, h.drexhage{at}erasmusmc.nl 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. RESEARCH DESIGN AND 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. Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 3 July 2008. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not