Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Identification of JAK1 as a Candidate Inflammatory Signalling Pathway by Genome-Wide Expression Profiling in Monocytes from Patients with Behcet's Disease.
Direskeneli3, Haner, Boyle1, Joseph J., Ozdemir3, Filiz T., Yilmaz2, Vuslat, Eksioglu-Demiralp3, Emel, Haskard1, Dorian, Saruhan-Direskeneli2, Guher
Both innate and adaptive immune responses are observed in Behcet's Disease (BD). We aimed to obtain a global view of the immune/inflammatory activity in BD compared to Familial Mediterranean Fever (FMF), a classical, autoinflammatory disease.
Twenty-eight patients with BD (F/M: 9/19, mean age: 33.4 years), 13 with FMF (F/M: 9/4, mean age: 30.4 years) and 21 healthy controls (HC) (F/M: 11/10, mean age: 30.6 years) were enrolled to the study. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) microarrays on an Affymetrix platform using CD14+ monocyte and CD4+T lymphocyte subsets isolated by microbeads from peripheral blood mononuclear cells. Data was analysed with Genespring (Version 10.0) software. RT-PCR was performed for the validation of JAK1 expression.
Among 28792 transcripts analysed, in CD14+ monocytes, 1188 transcripts reached a significant difference level with a minimum 2-fold difference observed in 279 genes. In CD4+T-lymphocytes, 2880 transcripts showed significant difference with at least 2-fold difference in 109 genes. In CD14+ monocytes of BD patients, oxysterol binding protein-like-8 (OSBPL8)(3.8 fold), cell-division-cycle-27 homolog (S. cerevisiae) (CDC27)(3.1 fold), myeloid/lymphoid or mixed-lineage leukemia-3 (MLL3)(3.1 fold), PHD finger protein-3 (PHF3)(2.9 fold) and BCL2-associated × protein (BAX)(2.7 fold) had the highest expressions. However, in principal component analysis, Januse-kinase-1 (JAK1)(2.6 fold) and metallothionein 1X, (MT1X)(2.1 fold) appeared to be the dominant molecules associated with immune/inflammatory signalling pathways. Validation by RT-PCR also showed an increased JAK1 expression (fold increase compared to GAPDH: BD: 9.5 vs FMF: 5.1 vs HC: 7.3, p=0.07, BD vs FMF: p=0.04).
Whole-genome microarray analysis demonstrated a selective activation of BD monocytes compared to FMF, suggesting their critical role between innate and adaptive immune responses. Activation of JAK1 through various cytokines such as IL-2, IL-6, IL-15 and interferon-gamma may be one of the dominant signaling pathways driving inflammation in BD.
To cite this abstract, please use the following information:
Direskeneli, Haner, Boyle, Joseph J., Ozdemir, Filiz T., Yilmaz, Vuslat, Eksioglu-Demiralp, Emel, Haskard, Dorian, et al; Identification of JAK1 as a Candidate Inflammatory Signalling Pathway by Genome-Wide Expression Profiling in Monocytes from Patients with Behcet's Disease. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2200