Distinct monocyte gene-expression profiles in autoimmune diabetes.
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.


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.
Padmos
Roos C
RC
Department of Immunology, Erasmus MC, Rotterdam, the Netherlands.
Schloot
Nanette C
NC
Beyan
Huriya
H
Ruwhof
Cindy
C
Staal
Frank J T
FJ
de Ridder
Dick
D
Aanstoot
Henk-Jan
HJ
Lam-Tse
Wai Kwan
WK
de Wit
Harm
H
de Herder
Christian
C
Drexhage
Roos C
RC
Menart
Barbara
B
Leslie
R David
RD
Drexhage
Hemmo A
HA
D000328:Adult; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D002648:Child; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D016207:Cytokines; D000683:Serum Amyloid P-Component; D000099153:Pentraxins