Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microsomal epoxide hydrolase catalyses the hydrolysis of epoxides to water-soluble trans-dihydrodiols. We studied the expression of the hydrolase in synovial tissue samples from patients with osteoarthritis (n = 20), rheumatoid arthritis (n = 36), ankylosing spondylitis (n = 10) or psoriatic arthritis (n = 15) by use of immunohistochemistry with videodensitometric quantification of staining. Strong immunostaining for microsomal epoxide hydrolase was detected in tunica media of synovial blood vessels and moderate staining in synovial lining cells. Experiments with antibodies against CD68 and CLA suggested that both type A (macrophage-like) and type B lining cells (fibroblast-like synoviocytes) express the hydrolase. In addition, some of the subsynovial fibroblast-like cells, histiocytes and monocytes were intensively stained for microsomal epoxide hydrolase. In general, there were no major differences in the intensity of immunostaining for the hydrolase between the diagnostic groups. The enzyme may be involved in local hydrolysis of epoxide metabolites of endo- and xenobiotics in synovial tissue.
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PMID:Immunohistochemical detection of microsomal epoxide hydrolase in human synovial tissue. 1057 13

At present only few biological data are available to indicate whether psoriatic arthritis (PsA) is part of the spondyloarthropathy (SpA) concept, whether it is a separate disease entity or a heterogeneous disease group with oligoarticular/axial forms belonging to SpA and polyarticular forms resembling rheumatoid arthritis (RA). To address this issue with regard to peripheral synovitis, we compared the synovial characteristics of PsA with those of ankylosing spondylitis (AS)/undifferentiated SpA (USpA) and RA, and compared the synovium of oligoarticular versus polyarticular PsA. Synovial biopsies were obtained from patients with RA, nonpsoriatic SpA (AS + USpA), and oligoarticular and polyarticular PsA. The histological analysis included examination(s) of the lining layer thickness, vascularity, cellular infiltration, lymphoid aggregates, plasma cells and neutrophils. Also, we performed immunohistochemical assessments of CD3, CD4, CD8, CD20, CD38, CD138, CD68, CD163, CD83, CD1a, CD146, alphaVbeta3, E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, S100A12, intracellular citrullinated proteins and major histocompatibility complex (MHC)-human cartilage (HC) gp39 peptide complexes. Comparing SpA (PsA + AS + USpA) with RA, vascularity, and neutrophil and CD163+ macrophage counts were greater in SpA (P < 0.05), whereas lining layer thickness and the number of CD83+ dendritic cells were greater in RA (P < 0.05). In RA, 44% of samples exhibited positive staining for intracellular citrullinated proteins and 46% for MHC-HC gp39 peptide complexes, whereas no staining for these markers was observed in SpA samples. We excluded influences of disease-modifying antirheumatic drug and/or corticosteroid treatment by conducting systematic analyses of treated and untreated subgroups. Focusing on PsA, no significant differences were observed between PsA and nonpsoriatic SpA. In contrast, vascularity (P < 0.001) and neutrophils were increased in PsA as compared with RA (P = 0.010), whereas staining for intracellular citrullinated proteins and MHC-HC gp39 peptide complexes was exclusively observed in RA (both P = 0.001), indicating that the same discriminating features are found in PsA and other SpA subtypes compared with RA. Exploring synovial histopathology between oligoarticular and polyarticular PsA, no significant differences were noted. Moreover, intracellular citrullinated proteins and MHC-HC gp39 peptide complexes, which are specific markers for RA, were observed in neither oligoarticular nor polyarticular PsA. Taken together, these data indicate that the synovial histopathology of PsA, either oligoarticular or polyarticular, resembles that of other SpA subtypes, whereas both groups can be differentiated from RA on the basis of these same synovial features, suggesting that peripheral synovitis in PsA belongs to the SpA concept.
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PMID:Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis. 1589 64

Patients with ankylosing spondylitis (AS) have an increased risk for cardiovascular mortality. The circulating ox-LDL/LDL ratio is associated with subclinical atherosclerosis in patients with systemic lupus erythematosus. In this study, we found that the ox-LDL/LDL ratio was increased in AS patients. The levels of serum RANKL and HMGB1 were also elevated in AS patients, and the number of CD68+/RANK+ cells was increased in peripheral blood from AS patients. 0.03% ox-LDL in LDL, similar to the ox-LDL/LDL ratio in peripheral blood from AS patients, promoted cytoplasmic translocation and release of HMGB1 as well as RANK expression. Further investigation evidenced that ox-LDL-induced EGR1 expression contributed to the cytoplasmic translocation of HMGB1 and CD68 assisted the secretion of HMGB1 from cytoplasm to extracellular matrix. Extracellular HMGB1 induced RANK expression in CD68+ mononuclear cells, forming osteoclast precursors that were differentiated to osteoclasts in response to RANKL. Taken together, these results suggested that the changes, including ox-LDL/LDL ratio, CD68+/RANK+ cells number, and the levels of RANKL and HMGB1 in AS patients, favored osteoclastogenesis.
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PMID:Oxidized low-density lipoprotein promotes osteoclast differentiation from CD68 positive mononuclear cells by regulating HMGB1 release. 2914 89

Xanthomatous sialadenitis (XS) is rarely reported. Here we report XS in a case of HLA-B27-positive ankylosing spondylitis showing also anti-MAG-positive polyneuropathy with IgM-kappa dysimmunoglobulinemia/paraproteinemia, lung small cell carcinoma and buccal squamous cell carcinoma (SCC). The lesions were identified in submandibular and labial minor salivary glands of a neck dissection specimen (made during a buccal 1.7 cm large SCC resection procedure). The oral SCC was resected at 8 months after the diagnosis of the lung small cell carcinoma (with skull dome metastases, revealed by a superior cava syndrome) and at 2 months after radiotherapy. The microscopic XS-lesions consisted in multifocal accumulations of CD68-positive macrophages. Plasmocyte-abundant foci (CD138-positive) were extra-xanthomatous (atrophic parenchyma, zones of adipose involution). CD138 was also expressed in ductal cells and in acini (focally). In conclusion, we report XS of submandibular and labial minor salivary glands, occurring in the context of a HLA-B27-positive ankylosing spondylitis, polyneuropathy with IgM-kappa dysimmunoglobulinemia and anti-MAG antibodies in a case of small cell lung carcinoma (treated by radio-chemotherapy) and oral SCC.
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PMID:Xanthomatous sialadenitis: Autoimmune- or treatment-induced lesions? 2939 21