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Distinct monocyte gene-expression profiles in autoimmune diabetes.

Padmos RC, Schloot NC, Beyan H, Ruwhof C, Staal FJ, de Ridder D, Aanstoot HJ, Lam-Tse WK, de Wit H, de Herder C, Drexhage RC, Menart B, Leslie RD, Drexhage HA, LADA Consorti - Diabetes (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Erasmus MC, Rotterdam, the Netherlands.

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.

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Color-coded correlation matrix illustrating pairwise correlations between the expression levels of the 24 genes aberrantly expressed in patients with various forms of diabetes (Table 1). Blue squares indicate negative correlations; red squares indicate positive correlations. The color intensities code for the strength of the correlations. Also, a dendrogram is presented as a result of hierarchical cluster analysis with the use of correlation coefficients. The dendrogram shows two gene-expression clusters.
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f1: Color-coded correlation matrix illustrating pairwise correlations between the expression levels of the 24 genes aberrantly expressed in patients with various forms of diabetes (Table 1). Blue squares indicate negative correlations; red squares indicate positive correlations. The color intensities code for the strength of the correlations. Also, a dendrogram is presented as a result of hierarchical cluster analysis with the use of correlation coefficients. The dendrogram shows two gene-expression clusters.

Mentions: Recently, we reported a signature of 18 inflammatory-related genes in monocytes of bipolar patients (11); activated monocytes are thought to play a role in the pathogenesis of bipolar disorder (12,13). Given the reported association between bipolar disorder and autoimmune diabetes (14), and given the possible central role of monocytes in both disorders, we tested this set of 18 proinflammatory monocyte genes in patients with autoimmune diabetes. To these 18 monocyte genes, we added 7 genes identified in a whole-genome expression profile of a set of juvenile-onset type 1 diabetic patients who had been compared with healthy control subjects and type 2 diabetic patients (see supplementary Fig. 1 [available in an online appendix at http://dx.doi.org/10.2337/db08-0496]). Thus, using quantitative RT-PCR (Q-PCR), we validated abnormal expression of 25 monocyte activation genes in latent autoimmune diabetes of the adult (LADA), adult-onset type 1 diabetic and juvenile-onset type 1 diabetic patients, and, as controls, type 2 diabetic patients and healthy subjects.


Distinct monocyte gene-expression profiles in autoimmune diabetes.

Padmos RC, Schloot NC, Beyan H, Ruwhof C, Staal FJ, de Ridder D, Aanstoot HJ, Lam-Tse WK, de Wit H, de Herder C, Drexhage RC, Menart B, Leslie RD, Drexhage HA, LADA Consorti - Diabetes (2008)

Color-coded correlation matrix illustrating pairwise correlations between the expression levels of the 24 genes aberrantly expressed in patients with various forms of diabetes (Table 1). Blue squares indicate negative correlations; red squares indicate positive correlations. The color intensities code for the strength of the correlations. Also, a dendrogram is presented as a result of hierarchical cluster analysis with the use of correlation coefficients. The dendrogram shows two gene-expression clusters.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2551688&req=5

f1: Color-coded correlation matrix illustrating pairwise correlations between the expression levels of the 24 genes aberrantly expressed in patients with various forms of diabetes (Table 1). Blue squares indicate negative correlations; red squares indicate positive correlations. The color intensities code for the strength of the correlations. Also, a dendrogram is presented as a result of hierarchical cluster analysis with the use of correlation coefficients. The dendrogram shows two gene-expression clusters.
Mentions: Recently, we reported a signature of 18 inflammatory-related genes in monocytes of bipolar patients (11); activated monocytes are thought to play a role in the pathogenesis of bipolar disorder (12,13). Given the reported association between bipolar disorder and autoimmune diabetes (14), and given the possible central role of monocytes in both disorders, we tested this set of 18 proinflammatory monocyte genes in patients with autoimmune diabetes. To these 18 monocyte genes, we added 7 genes identified in a whole-genome expression profile of a set of juvenile-onset type 1 diabetic patients who had been compared with healthy control subjects and type 2 diabetic patients (see supplementary Fig. 1 [available in an online appendix at http://dx.doi.org/10.2337/db08-0496]). Thus, using quantitative RT-PCR (Q-PCR), we validated abnormal expression of 25 monocyte activation genes in latent autoimmune diabetes of the adult (LADA), adult-onset type 1 diabetic and juvenile-onset type 1 diabetic patients, and, as controls, type 2 diabetic patients and healthy subjects.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Erasmus MC, Rotterdam, the Netherlands.

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.

Show MeSH
Related in: MedlinePlus