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

Cardiovascular Sciences Centre, Imperial College, London, United Kingdom
Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
Marmara University, School of Medicine, Istanbul, Turkey


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
DOI: 10.1002/art.29964

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