Association of Circulating COMP and YKL-40 as Markers of Metabolic Changes of Cartilage with Adipocytokines in Juvenile Idiopathic Arthritis

Abstract

The aim of this study was to evaluate the association of circulating cartilage oligomeric matrix protein (COMP) and human cartilage glycoprotein-39 (YKL-40) as markers of metabolic changes of cartilage, with leptin, adiponectin, and resistin in juvenile idiopathic arthritis (JIA) patients before and after treatment. A significant decrease of COMP and an increase of YKL-4 were found in blood of untreated patients. JIA treatment leading to clinical improvement resulted in normalization of COMP levels only. Concentrations of both markers in treated patients, while showing no clinical improvement, differed from those in controls and patients with remission. The leptin level decreased (p < 0.05) in untreated patients; however, concentrations of adiponectin and resistin increased (p < 0.05) as compared to controls. JIA treatment resulted in normalization of adipocytokine levels in remissive patients but not those with active JIA. Untreated patients showed a correlation between COMP and leptin, adiponectin, and body mass index (BMI) and between YKL-40 and leptin, adiponectin, BMI, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). In inactive JIA, a correlation between YKL-40 and leptin was shown. Treated patients with an active JIA demonstrated a correlation between COMP and adiponectin and between YKL-40 and leptin, adiponectin, BMI, CRP, and ESR. The results of this work indicate that leptin and adiponectin but not resistin may be involved in the development and progression of joint dysfunction in JIA. Additionally, we suggest that YKL-40 may be a useful biomarker of disease activity and may be used to assess treatment towards remission, as compared to COMP.Metabolites 2020, 10, 61 2 of 11 remodeling, manifested by significant changes of the circulating markers of cartilage turnover, including total glycosaminoglycans (GAGs) and their particular types such as keratan sulphate, chondroitin sulphate, hyaluronic acid, as well as chondroitin sulphate 846 epitope [5][6][7][8].Among ECM components, which are indicators of the cartilage breakdown, there are also listed components synthesized by chondrocytes, i.e., cartilage oligomeric matrix protein (COMP) as well as human cartilage glycoprotein 39 (YKL-40), that are so far not evaluated in JIA patients. The first one is a non-collagenous glycoprotein, binding to aggrecan; fibronectin; and collagen types I, II, and IX, which seem to play a role in the structure of fibrils and in maintenance of the collagen network [9,10]. Whereas YKL-40, a glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate autoantigen in rheumatoid arthritis. It has been shown that YKL-40 binds to some important components in the cartilage extracellular matrix, i.e., proteoglycans and collagens, influencing their production and assembly [11][12][13][14]. Several authors have investigated the relationship between circulating COMP or YKL-40 and the condition of articular cartilage in adult patients with and without any r...

Relationship of C-Reactive Proteins and Erythrocyte Sedimentation Rate with Active Disease in Patients with Juvenile Rheumatoid Arthritis

“…This is Guillaume et al reported that the arthritic group was in remission more often than in other types. Similarly, Aggarwal et al found that 45% of patients in the nonlinear group and 20% of patients in the polyarticular group were in remission [18][19] . In our study the majority of the population had late illnesses and this may be a reason for the presentation of all subtypes.…”

“…This is different from the West, where polyarthritis and systemic onset disease are more common than polyarthritis. Moreover, while all the studies in Pakistan, India and Sri Lanka were hospitalized, the studies in Western countries were population-based studies, so comparisons are difficult 18 . Comparing the different subtypes of the active disease group and the remission group, it was found in our study that only one type of disease was not negative.…”

Alterations of Extracellular Matrix Components in the Course of Juvenile Idiopathic Arthritis

“…The ECM components metabolism are related both to the change in the rate of the matrix components degradation processes, which takes place in the presence of excess of ROS (assessed by spectrophotometric method) and proteolytic enzymes-especially MMPs and ADAMTS proteins (assessed by ELISA), as well as to the biosynthesis of matrix compounds [31,32,111]. Treatment that results in clinical stabilization did not contribute to the normalization of markers of cartilage turnover such as chondroitin sulphate [127], keratan sulphate [81], YKL-40 [126] as well as of MMP-3 [43,54], TIMP-1 [60] and TAS concentrations in patients' blood [54]. JIA therapy with the use of methotrexate, glucocorticoids and the non-steroidal anti-inflammatory drugs, may alleviate symptoms by reducing pain and inflammation, but destruction of connective tissues often continues unabated [43,73].…”

“…In the course of JIA, there occurred a dysregulation of cartilaginous ECM remodeling, especially aggrecan, manifested by significant changes of the circulating markers of cartilage turnover, including total glycosaminoglycans (assessed by spectrophotometry method) and their particular types such as keratan sulphate (assessed by enzyme-linked immunosorbent assay, ELISA), chondroitin sulphate (assessed by electrophoretic method), hyaluronic acid (assessed by ELISA) as well as chondroitin sulphate 846 epitope (assessed by ELISA) [54,73,81]. Among ECM components, there are also molecules synthesized by chondrocytes, i.e., cartilage oligomeric matrix protein (COMP) and human cartilage glycoprotein 39 (YKL-40) (assessed by ELISA) that can be useful biomarkers of cartilage turnover [126]. These markers can be a useful diagnostic tool to evaluate cartilage condition in JIA patients and could be used to assess treatment towards remission.…”

Concerted Actions by PIICP, CTXII, and TNF-α in Patients with Juvenile Idiopathic Arthritis

“…These studies were approved by the Local Ethics Committee of the Medical University of Silesia in Katowice (KNW/0022/KB/81/15). Informed consent was obtained from the participants or their legal guardians, according to the ethical guidelines of the Declaration of Helsinki, as part of the continuation of our earlier research [ 16 ].…”