Details

Autor(en) / Beteiligte

• PADMOS, Roos C
• SCHLOOT, Nanette C
• DREXHAGE, Roos C
• MENART, Barbara
• LESLIE, R. David
• DREXHAGE, Hemmo A
• BEYAN, Huriya
• RUWHOF, Cindy
• STAAL, Frank J. T
• DE RIDDER, Dick
• AANSTOOT, Henk-Jan
• LAM-TSE, Wai Kwan
• DE WIT, Harm
• DE HERDER, Christian

Titel

Distinct Monocyte Gene-Expression Profiles in Autoimmune Diabetes

Ist Teil von

• Diabetes (New York, N.Y.), 2008-10, Vol.57 (10), p.2768-2773

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. * * Members of the LADA Consortium can be found in the appendix . Accepted June 21, 2008. Received April 11, 2008. DIABETES