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.

Distinct monocyte Gene-Expression profiles in autoimmune diabetes / Padmos, Roos C.; Schloot, Nanette C.; Beyan, Huriya; Ruwhof, Cindy; Staal, Frank J. T.; De Ridder, Dick; Aanstoot, Henk-Jan; Lam-Tse, Wai Kwan; De Wit, Harm; De Herder, Christian; Drexhage, Roos C.; Menart, Barbara; Leslie, R. David; Drexhage, Hemmo A.; Hawa, M; Pozzilli, P.; Williams, R.; Brophy, S.; Davies, H.; Beck-Nielsen, H.; Yderstraede, K.; Hadden, D.; Hunter, S.; Buzzetti, R.; Scherbaum, W.; Siessler, J.; Schloot, Nc; Kolb, H.; Schernthaner, G.; Tuomilehto, J.; Sarti, C.; De Leiva, A.; Mauricio, D.; Brugues, E.; Thivolet, C.. - In: DIABETES. - ISSN 0012-1797. - 57:10(2008), pp. 2768-2773. [10.2337/db08-0496]

Distinct monocyte Gene-Expression profiles in autoimmune diabetes

Pozzilli, P.;Williams, R.;Buzzetti, R.;Sarti, C.;
2008

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.
2008
adult; C-Reactive Protein; child; cluster analysis; cytokines; Diabetes Mellitus, Type 1; female; Gene Expression Profiling; humans; male; monocytes; reverse transcriptase polymerase chain reaction; Serum Amyloid P-Component; internal medicine; endocrinology, diabetes and metabolism
01 Pubblicazione su rivista::01a Articolo in rivista
Distinct monocyte Gene-Expression profiles in autoimmune diabetes / Padmos, Roos C.; Schloot, Nanette C.; Beyan, Huriya; Ruwhof, Cindy; Staal, Frank J. T.; De Ridder, Dick; Aanstoot, Henk-Jan; Lam-Tse, Wai Kwan; De Wit, Harm; De Herder, Christian; Drexhage, Roos C.; Menart, Barbara; Leslie, R. David; Drexhage, Hemmo A.; Hawa, M; Pozzilli, P.; Williams, R.; Brophy, S.; Davies, H.; Beck-Nielsen, H.; Yderstraede, K.; Hadden, D.; Hunter, S.; Buzzetti, R.; Scherbaum, W.; Siessler, J.; Schloot, Nc; Kolb, H.; Schernthaner, G.; Tuomilehto, J.; Sarti, C.; De Leiva, A.; Mauricio, D.; Brugues, E.; Thivolet, C.. - In: DIABETES. - ISSN 0012-1797. - 57:10(2008), pp. 2768-2773. [10.2337/db08-0496]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1196928
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