Background/Purpose: We aimed to identify the immune mechanism underlying gouty inflammation using microarrays analysis and modular gene expression signatures. 

Methods: Whole blood along with clinical and treatment data were collected from out-patients with gout. A total of 28 samples from 20 patients (18 males and 2 females; median age 53.5 years [range 39-82]; median disease duration 2.2 years [range 0-29.11]) and from 16 matched healthy controls were obtained. Thirteen patients had active disease at their first visit, and 7 had quiescent (intercritical) disease. Whole blood RNA was extracted using standard technologies and was hybridized to Illumina HT-12 chips. Genes differentially expressed (unpaired Student’s t-test) in the first visit of all gout or active gout patients (fold change ≥2 and a p<0.05), were selected for further consideration. Ingenuity Pathways Analysis was performed and we also adopted a module based data mining strategy, which can facilitate biomarker and biological knowledge discovery.

Results: Two hundred and four genes were found differentially expressed in gout patients at their first visit regardless of clinical activity. When active patients were selected, 184 transcripts were found dysregulated. Innate immunity genes related to the interleukin-1 (IL1) signaling pathway were up-regulated (ORM1/ORM2, BNIP3L, EPB49, defensins, myeloperoxidase, elastase), whereas genes involved in adaptive immunity were down-regulated (CD79A, CD79B, CBR complex). Modular analysis permitted us to visualize alterations in 174/260 pre-defined modules. Of those, transcripts related to innate immunity cell types, including neutrophils, were increased. Those related to B cells, T cells, NK/cytotoxic and plasma cells were decreased. Interestingly, transcripts related to an early erythrocyte cell population previously described in other IL1-mediated diseases such as systemic onset Juvenile Idiopathic Arthritis (sJIA)/Still’s disease and S. aureus infections were upregulated. In addition, modules related to inflammation and cell death were up-regulated, while those of proliferation, cell cycle, and mitochondrial stress were down-regulated. This modular pattern might represent a biomarker of innate immunity/IL1-related diseases.

Conclusion: Patients with gout display a blood transcriptional profile similar to that seen in IL-1 dominant or autoinflammatory diseases. This fits with the current knowledge about the involvement of the inflammasome in gout and patients response to IL-1 blockade. This profile is easily interpreted using our previously described modular analysis framework. Although larger, prospective studies including newly diagnosed patients on no treatment are needed to confirm these findings, our data suggest that it is possible to use blood gene expression analysis to identify molecular and cellular pathways linked to dysregulation of innate immunity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/microarray-analysis-of-acute-and-intercritical-gout/