YKL-40 and cytokines - a New Diagnostic Constellation in Rheumatoid Arthritis?

BACKGROUND: Rheumatoid arthritis (RA) causes chronic inflammation and alteration of articular tissue and joints. The pathogenesis of the disease remains unclear although it is known that proinflammatory cytokines play a major role in its induction. YKL-40 is a chitinase-like glycoprotein produced by activated macrophages, neutrophils, arthritic chondrocytes and cancer cells. It has been shown that YKL-40 is implicated in tissue remodeling, angiogenesis and inflammation. AIM: to investigate serum and synovial YKL-40 levels in relation to IL-1ß, TNF-α, and IL-6 in RA patients. MATERIALS AND METHODS: Serum and synovial concentrations of YKL-40, TNF-α, IL- 6, and IL-1ß were determined by ELISA in 39 patients (mean age 53.18 ± 16.54 yrs) with active RA. RESULTS: Serum YKL-40 levels were increased in all patients. The highest levels were found in synovial fluid (P<0.01). Our study showed a strong association between serum and synovial levels of YKL-40 and serum TNF-α and IL-1 ß (P<0.05). CONCLUSION: This is the first study finding a significant correlation between serum TNF-α and IL-1ß and YKL-40 in active RA. We suggest that these molecules together might play a dominant role in the pathogenesis and disease activity and could possibly serve as a new diagnostic constellation in rheumatoid arthritis.

Glioblastoma multiforme classified as mesenchymal subtype.

INTRODUCTION: Recently, researchers have been considering as adverse prognostic factors in primary glioblastomas not only clinical indicators but also various cellular, genetic and immunological markers. The aim of the present article was to report a case of primary glioblastoma multiforme with poor survival in a patient after surgical intervention, and to determine the unfavorable prognostic markers. CASE REPORT: We present a 71-year-old man with histologically verified glioblastoma multiforme and a postoperative survival of 48 days. The patient did not receive any radiotherapy and adjuvant therapy with temozolomide because of the short survival. Serum and transcription levels of TNF-α, CD44, YKL-40 and IL-6 were determined by molecular-biological and immunological analyses. We found very high transcription levels of the genes CD44, YKL-40 and IL-6, increased gene expression of TNF-α, and elevated serum concentrations of TNF-α, YKL-40 and IL-6 and reduced serum concentration of CD44. CONCLUSION: Molecular-biological and immunological analyses support the hypothesis that glioblastoma multiforme is presented by a heterogeneous group of glial tumors with different clinical course and prognosis. The high expression levels of TNF-α, CD44, YKL-40, and IL-6 indicate that the tumor can be categorized as mesenchymal subtype of glioblastoma multiforme, which accounts for the rapid clinical course and lethal outcome of the condition.

YKL-40--a novel biomarker in clinical practice?

YKL-40 is a recently discovered human glycoprotein which is related in amino acid sequence to the chitinase protein family, but has no chitinase activity. The present review focuses on the expression and regulation of YKL-40, its clinical significance, detection techniques and outlines the advantages and limitations of its application as a novel biomarker. YKL-40 is expressed and secreted by macrophages, neutrophils, fibroblast-like synovial cells, chondrocytes, vascular smooth muscle cells and hepatic stellate cells. The complete biological function of YKL-40 is unclear, and it is not yet known to have a specific receptor. However, its pattern of expression is associated with pathogenic processes related to inflammation, extracellular tissue remodeling, fibrosis and solid carcinomas. It is assumed that YKL-40 plays a role in cancer cell proliferation, survival, invasiveness and in the regulation of cell-matrix interactions. It is suggested that YKL-40 is a marker associated with a poorer clinical outcome in genetically defined subgroups of different tumors. YKL-40 was recently introduced into clinical practice and its application is still restricted. There are a few techniques available for its detection and the commercially accessible kits are limited, too. Elucidation of YKL-40 functions is an important objective of future studies as it seems likely that YKL-40 might have a significant role in cancer invasiveness and could possibly serve as an attractive target in anticancer therapy.