Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets

Abstract

BackgroundChronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, but their pathogenesis is still not well understood.It is also not well known if distinct changes in gene expression characterize these diseases and if these patterns can discriminate between diseased and control patients and/or stratify the disease. The main focus of our work was the identification of novel markers that overlap among the 3 diseases or discriminate them from each other.MethodsDiseased (n = 13, n = 15 and n = 12 in IBD, psoriasis and RA respectively) and healthy patients (n = 18) were recruited based on strict inclusion and exclusion criteria; peripheral blood samples were collected by clinicians (30 ml) in Venous Blood Vacuum Collection Tubes containing EDTA and peripheral blood mononuclear cells were separated by Ficoll gradient centrifugation. RNA was extracted using Trizol reagent. Gene expression data was obtained using TaqMan Low Density Array (TLDA) containing 96 genes that were selected by an algorithm and the statistical analyses were performed in Prism by using non-parametric Mann-Whitney U test (P-values < 0.05).ResultsHere we show that using a panel of 96 disease associated genes and measuring mRNA expression levels in peripheral blood derived mononuclear cells; we could identify disease-specific gene panels that separate each disease from healthy controls. In addition, a panel of five genes such as ADM, AQP9, CXCL2, IL10 and NAMPT discriminates between all samples from patients with chronic inflammation and healthy controls. We also found genes that stratify the diseases and separate different subtypes or different states of prognosis in each condition.ConclusionsThese findings and the identification of five universal markers of chronic inflammation suggest that these diseases have a common background in pathomechanism, but still can be separated by peripheral blood gene expression. Importantly, the identified genes can be associated with overlapping biological processes including changed inflammatory response. Gene panels based on such markers can play a major role in the development of personalized medicine, in monitoring disease progression and can lead to the identification of new potential drug targets in chronic inflammation.

Novel specific microRNA biomarkers in idiopathic inflammatory bowel disease unrelated to disease activity

“…[13][14][15][16][17][18] In this study, we identified miR-31, miR-146a, miR-206, and miR-424 as novel miRNA biomarkers that are commonly and specifically expressed in the freshfrozen tissue of colonic mucosa from inflammatory bowel disease patients compared with colonic mucosa control patients. The dysregulated expression of four miRNAs in both ulcerative colitis and Crohn disease suggests that these miRNAs might be involved in the regulation of the common pathophysiological pathway leading to inflammatory bowel disease.…”

The promises of personalized medicine

“…The presence of genomic markers, such as mutations in epidermal growth regulator factor (EGFR) or KRAS, may be decisive for the successful treatment of solid and non-solid malignancies, and such information is being increasingly recognized and implemented by regulatory authorities. There is also increasing evidence for the application of personalized medicine in immunological and/or inflammatory diseases [21]. Personalized medicine is actually becoming accepted in oncology much more quickly due both to the diversity and potentially lethal character of the disease and to the narrow therapeutic index and low benefit-risk ratio of the drugs used.…”

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease

“…Thus, it is likely that AQP9 may contribute to neuroinflammation as well, although not investigated. However, AQP9 expression is found in leukocytes (264), and has been found to be upregulated in peripheral blood derived mononuclear cells from patients with inflammatory diseases (461)(462)(463). Nevertheless, both AQP4 and AQP1 are orthodox aquaporins only permeable to water, whereas AQP9 shows a broad permeability specter, suggesting that AQP9 may serve other roles as well.…”