Distinct monocyte gene-expression profiles in autoimmune diabetes. Export

@article{citeulike:4062172, 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.}, author = {Padmos, R. C. and Schloot, N. C. and Beyan, H. and Ruwhof, C. and Staal, F. J. and de Ridder, D. and Aanstoot, H. J. and Lam-Tse, W. K. and de Wit, H. and de Herder, C. and Drexhage, R. C. and Menart, B. and Leslie, R. D. and Drexhage, H. A. and {}}, citeulike-article-id = {4062172}, citeulike-linkout-0 = {http://dx.doi.org/10.2337/db08-0496}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18599519}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18599519}, doi = {10.2337/db08-0496}, issn = {1939-327X}, journal = {Diabetes}, keywords = {dm, ma, pbmc}, month = {October}, number = {10}, pages = {2768--2773}, posted-at = {2009-02-17 03:03:16}, priority = {2}, title = {Distinct monocyte gene-expression profiles in autoimmune diabetes.}, url = {http://dx.doi.org/10.2337/db08-0496}, volume = {57}, year = {2008} }

TY - JOUR ID - citeulike:4062172 L3 - citeulike-article-id:4062172 N2 - 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. IS - 10 JF - Diabetes SN - 1939-327X EP - 2773 TI - Distinct monocyte gene-expression profiles in autoimmune diabetes. VL - 57 SP - 2768 KW - dm KW - ma KW - pbmc AU - Padmos, RC AU - Schloot, NC AU - Beyan, H AU - Ruwhof, C AU - Staal, FJ AU - de Ridder, D AU - Aanstoot, HJ AU - Lam-Tse, WK AU - de Wit, H AU - de Herder, C AU - Drexhage, RC AU - Menart, B AU - Leslie, RD AU - Drexhage, HA PY - 2008/10// UR - http://dx.doi.org/10.2337/db08-0496 ER -