Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psoriatic arthritis (PsA) is a chronic and erosive form of arthritis of unknown cause. We aimed to characterize the PsA phenotype using gene expression profiling and comparing it with healthy control subjects and patients rheumatoid arthritis (RA). Peripheral blood cells (PBCs) of 19 patients with active PsA and 19 age- and sex-matched control subjects were used in the analyses of PsA, with blood samples collected in PaxGene tubes. A significant alteration in the pattern of expression of 313 genes was noted in the PBCs of PsA patients on Affymetrix U133A arrays: 257 genes were expressed at reduced levels in PsA, and 56 genes were expressed at increased levels, compared with controls. Downregulated genes tended to cluster to certain chromosomal regions, including those containing the psoriasis susceptibility loci PSORS1 and PSORS2. Among the genes with the most significantly reduced expression were those involved in downregulation or suppression of innate and acquired immune responses, such as SIGIRR, STAT3, SHP1, IKBKB, IL-11RA, and TCF7, suggesting inappropriate control that favors proin-flammatory responses. Several members of the MAPK signaling pathway and tumor suppressor genes showed reduced expression. Three proinflammatory genes--S100A8, S100A12, and thioredoxin--showed increased expression. Logistic regression and recursive partitioning analysis determined that one gene, nucleoporin 62 kDa, could correctly classify all controls and 94.7% of the PsA patients. Using a dataset of 48 RA samples for comparison, the combination of two genes, MAP3K3 followed by CACNA1S, was enough to correctly classify all RA and PsA patients. Thus, PBC gene expression profiling identified a gene expression signature that differentiated PsA from RA, and PsA from controls. Several novel genes were differentially expressed in PsA and may prove to be diagnostic biomarkers or serve as new targets for the development of therapies.
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PMID:Microarray analyses of peripheral blood cells identifies unique gene expression signature in psoriatic arthritis. 1662 21

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis. Pathogenesis is incompletely understood and pathophysiological role of synovium is just beginning to be elucidated. PsA could be considered an enthesal disease and this hypothesis is the link between mechanical stress (entheses) and immunologically active tissue (synovium). Histologically, PsA is characterized by lining layer hyperplasia, diffuse infiltrate of B, T, macrophages and dendritic cells associated with neutrophils' proliferation and angiogenesis. T cells are present, and oligoclonal T-cell expansions have been demonstrated in both skin and synovium. Histological findings are associated with monocyte-derived cytokines expression, as Myeloid-related protein (S100A8/A9). They play an important role in intracellular functions and cytoskeleton-membrane interactions. S100A8/A9 has a role in the propagation and perpetuation of the inflammatory process in patients with psoriasis and PsA, because of an activated monocyte/macrophage system that involve, distal to the skin, the "enthesal-complex." Complement system can be considered part of the acute phase response as demonstrated by higher plasma levels of C3 and C4 complement components in PsA patients compared with healthy subjects. These abnormal levels are then reverted by anti-TNF drugs. Evidences of efficacy of anti-TNF are expressed by reduction of vascularity and immune cells in synovial tissue. Therefore, innate response generates high concentrations of inflammatory cytokines which promote effector functions of a variety of tissue cells and sustain the characteristic chronicity of synovitis. The challenge will be the development of molecules affecting the balance between innate and adaptive immunity without affecting beneficial functions of the perfect concert of immunological process.
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PMID:Immunomodulation in psoriatic arthritis: focus on cellular and molecular pathways. 2318 78