1. Distinct monocyte gene-expression profiles in autoimmune diabetes
- Author
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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., Immunology, and Pediatrics
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Biology ,medicine.disease_cause ,Pathophysiology ,Autoimmunity ,Proinflammatory cytokine ,Pathogenesis ,endocrinology ,male ,SDG 3 - Good Health and Well-being ,Internal medicine ,Diabetes mellitus ,Gene expression ,medicine ,Diabetes Mellitus ,humans ,diabetes and metabolism ,Type 1 diabetes ,child ,Monocyte ,adult ,Gene Expression Profiling ,medicine.disease ,cytokines ,Gene expression profiling ,reverse transcriptase polymerase chain reaction ,Serum Amyloid P-Component ,internal medicine ,Endocrinology ,medicine.anatomical_structure ,Diabetes Mellitus, Type 1 ,C-Reactive Protein ,female ,cluster analysis ,monocytes ,endocrinology, diabetes and metabolism ,Immunology ,Type 1 - 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.
- Published
- 2008