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

Mesko B, Poliska S, Szegedi A, Szekanecz Z, Palatka K, Papp M, Nagy L - BMC Med Genomics (2010)

Bottom Line: We also found genes that stratify the diseases and separate different subtypes or different states of prognosis in each condition.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.

ABSTRACT

Background: Chronic 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.

Methods: Diseased (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).

Results: Here 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.

Conclusions: These 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.

Show MeSH

Related in: MedlinePlus

Peripheral blood derived universal markers of chronic inflammation. Normalized mRNA levels of genes (with SD) showing significant differences between all the samples of chronic inflammatory diseases and healthy controls were generated from RT-QPCR measurements.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2874757&req=5

Figure 6: Peripheral blood derived universal markers of chronic inflammation. Normalized mRNA levels of genes (with SD) showing significant differences between all the samples of chronic inflammatory diseases and healthy controls were generated from RT-QPCR measurements.

Mentions: Importantly, we have identified five genes, ADM, AQP9, CXCL2, IL10 and NAMPT that show significant differences in expression levels between all the three conditions and control samples (Figure 6). These genes might be considered universal markers of chronic inflammation in PBMCs. Regarding pathway analysis that features the biological processes the genes are associated with; IL10 has the highest number of related biological processes (over 20) including lymphocyte, T and B cell proliferation, interleukin production and macrophage activation. ADM is related to 10 processes such as activation of MAPK-activity and interleukin-6 production; while AQP9, CXCL2 and NAMPT are only associated with a single process, urea transport, interleukin-18 production and neutrophil apoptosis, respectively (Figure 7).


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

Mesko B, Poliska S, Szegedi A, Szekanecz Z, Palatka K, Papp M, Nagy L - BMC Med Genomics (2010)

Peripheral blood derived universal markers of chronic inflammation. Normalized mRNA levels of genes (with SD) showing significant differences between all the samples of chronic inflammatory diseases and healthy controls were generated from RT-QPCR measurements.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874757&req=5

Figure 6: Peripheral blood derived universal markers of chronic inflammation. Normalized mRNA levels of genes (with SD) showing significant differences between all the samples of chronic inflammatory diseases and healthy controls were generated from RT-QPCR measurements.
Mentions: Importantly, we have identified five genes, ADM, AQP9, CXCL2, IL10 and NAMPT that show significant differences in expression levels between all the three conditions and control samples (Figure 6). These genes might be considered universal markers of chronic inflammation in PBMCs. Regarding pathway analysis that features the biological processes the genes are associated with; IL10 has the highest number of related biological processes (over 20) including lymphocyte, T and B cell proliferation, interleukin production and macrophage activation. ADM is related to 10 processes such as activation of MAPK-activity and interleukin-6 production; while AQP9, CXCL2 and NAMPT are only associated with a single process, urea transport, interleukin-18 production and neutrophil apoptosis, respectively (Figure 7).

Bottom Line: We also found genes that stratify the diseases and separate different subtypes or different states of prognosis in each condition.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.

ABSTRACT

Background: Chronic 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.

Methods: Diseased (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).

Results: Here 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.

Conclusions: These 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.

Show MeSH
Related in: MedlinePlus