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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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Related in: MedlinePlus

Serum levels of PTX3 in cluster 1–positive (n = 36) and –negative subjects (n = 73) (patients as well as control subjects). The definition was as follows: positive, ≥75% of the cluster 1 genes positive; negative, <75% of the cluster 1 genes positive. Groups were compared by ANCOVA analysis with age, sex, and BMI included in the model. Because normal distribution of PTX3 could not be obtained, ranks of PTX3 were used in the analysis (28).
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f2: Serum levels of PTX3 in cluster 1–positive (n = 36) and –negative subjects (n = 73) (patients as well as control subjects). The definition was as follows: positive, ≥75% of the cluster 1 genes positive; negative, <75% of the cluster 1 genes positive. Groups were compared by ANCOVA analysis with age, sex, and BMI included in the model. Because normal distribution of PTX3 could not be obtained, ranks of PTX3 were used in the analysis (28).

Mentions: In addition to monocyte gene analysis, we determined serum levels of IL-6, tumor necrosis factor–α, pentraxin 3 (PTX3), and CCL2 in patients and control subjects (for data see supplementary Fig. 2) and correlated gene expression levels to corresponding serum cytokine levels. Monocyte gene expression levels of PTX3 and IL6 (PTX3: r = 0.26, P = 0.004; IL-6: r = 0.23, P = 0.034; Spearman's correlation), but not of TNF and CCL2, correlated with serum protein levels. A possible explanation for this observed discrepancy between mRNA and protein expression levels is that serum levels of cytokines are more subject to confounders (e.g., BMI, glucose levels) than gene expression levels, as is suggested by our data (supplementary Fig. 2).


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)

Serum levels of PTX3 in cluster 1–positive (n = 36) and –negative subjects (n = 73) (patients as well as control subjects). The definition was as follows: positive, ≥75% of the cluster 1 genes positive; negative, <75% of the cluster 1 genes positive. Groups were compared by ANCOVA analysis with age, sex, and BMI included in the model. Because normal distribution of PTX3 could not be obtained, ranks of PTX3 were used in the analysis (28).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Serum levels of PTX3 in cluster 1–positive (n = 36) and –negative subjects (n = 73) (patients as well as control subjects). The definition was as follows: positive, ≥75% of the cluster 1 genes positive; negative, <75% of the cluster 1 genes positive. Groups were compared by ANCOVA analysis with age, sex, and BMI included in the model. Because normal distribution of PTX3 could not be obtained, ranks of PTX3 were used in the analysis (28).
Mentions: In addition to monocyte gene analysis, we determined serum levels of IL-6, tumor necrosis factor–α, pentraxin 3 (PTX3), and CCL2 in patients and control subjects (for data see supplementary Fig. 2) and correlated gene expression levels to corresponding serum cytokine levels. Monocyte gene expression levels of PTX3 and IL6 (PTX3: r = 0.26, P = 0.004; IL-6: r = 0.23, P = 0.034; Spearman's correlation), but not of TNF and CCL2, correlated with serum protein levels. A possible explanation for this observed discrepancy between mRNA and protein expression levels is that serum levels of cytokines are more subject to confounders (e.g., BMI, glucose levels) than gene expression levels, as is suggested by our data (supplementary Fig. 2).

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