Raised chondroitin sulfate epitopes and hyaluronan in serum from rheumatoid arthritis and osteoarthritis patients

Pothacharoen, Peraphan; Teekachunhatean, Supanimit; Louthrenoo, Worawit; Yingsung, Wannarat; Ongchai, Siriwan; Hardingham, Timothy E.; Kongtawelert, Prachya

doi:10.1016/j.joca.2005.10.005

Cited by 35 publications

(42 citation statements)

References 14 publications

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“…It has recently been demonstrated that a single chain phage display antibody GD3G7 also interacts with multiple decasaccharide sequences isolated from squid cartilage CS-E (63). Although the octasaccharides and the saturated counterparts (D-C-C-C and C-C-A-D), which were recognized by WF6, were isolated in this and previous studies (55) from shark cartilage CS chains, the epitopes are present in humans, since elevated levels of the epitopes have been detected by WF6 in sera from patients with osteoarthritis, rheumatoid arthritis (19), and ovarian cancers (20). In view of the findings that the above described antibodies, including WF6, interact with multiple oligosaccharides containing similar yet distinct sequences, we used molecular modeling to investigate possible common features shared by the preferred octasaccharides and absent from the nonpreferred octasaccharides.…”

Section: Tablementioning

confidence: 64%

“…It is reactive with shark CS-PGs, and the epitope was also detected in commercial CS preparations (CS-C and CS-D) from shark cartilage, but the antibody is unreactive with other glycosaminoglycans (GAGs) (25). An enzyme-linked immunosorbent assay (ELISA) has shown that this mAb detected an increased level of WF6 epitope in serum samples from patients of osteoarthritis and rheumatoid arthritis (19) and in those of ovarian cancer (20). The established specificity of the antibody and its restricted distribution among CS chains has suggested that the epitope is a specific sequence found in some but not all CS chains and is composed of sulfated disaccharides, including A unit (GlcUA␤1-3GalNAc(4-O-sulfate)), C unit (GlcUA␤1-3GalNAc(6-O-sulfate)), and D unit (GlcUA(2-O-sulfate)␤1-3GalNAc(6-O-sulfate)).…”

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confidence: 99%

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Two Related but Distinct Chondroitin Sulfate Mimetope Octasaccharide Sequences Recognized by Monoclonal Antibody WF6

Pothacharoen

Kalayanamitra

Deepa

et al. 2007

Journal of Biological Chemistry

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Chondroitin sulfate (CS) proteoglycans are major components of cartilage and other connective tissues. The monoclonal antibody WF6, developed against embryonic shark cartilage CS, recognizes an epitope in CS chains, which is expressed in ovarian cancer and variably in joint diseases. To elucidate the structure of the epitope, we isolated oligosaccharide fractions from a partial chondroitinase ABC digest of shark cartilage CS-C and established their chain length, disaccharide composition, sulfate content, and sulfation pattern. These structurally defined oligosaccharide fractions were characterized for binding to WF6 by enzyme-linked immunosorbent assay using an oligosaccharide microarray prepared with CS oligosaccharides derivatized with a fluorescent aminolipid. The lowest molecular weight fraction recognized by WF6 contained octasaccharides, which were split into five subfractions. The most reactive subfraction contained several distinct octasaccharide sequences. Two octasaccharides, ⌬D-C-C-C and ⌬C-C-A-D (where A represents GlcUA␤1-3GalNAc(4-O-sulfate), C is GlcUA␤1-3Gal-NAc(6-O-sulfate), D is GlcUA(2-O-sulfate)␤1-3GalNAc(6-Osulfate), ⌬C is ⌬ 4,5 HexUA␣1-3GalNAc(6-O-sulfate), and ⌬D is ⌬ 4,5 HexUA(2-O-sulfate)␣1-3GalNAc(6-O-sulfate)), were recognized by WF6, but other related octasaccharides, ⌬C-A-D-C and ⌬C-C-C-C, were not. The structure and sequences of both the binding and nonbinding octasaccharides were compared by computer modeling, which revealed a remarkable similarity between the shape and distribution of the electrostatic potential in the two different octasaccharide sequences that bound to WF6 and that differed from the nonbinding octasaccharides. The strong similarity in structure predicted for the two binding CS octasaccharides (⌬D-C-C-C and ⌬C-C-A-D) provided a possible explanation for their similar affinity for WF6, although they differed in sequence and thus form two specific mimetopes for the antibody. Chondroitin sulfate proteoglycans (CS-PGs)5 are expressed on the surface of most cells and in extracellular matrices in vertebrates, where CS is linked to a wide range of core protein families. They are increasingly implicated as important regulators of many biological processes, contributing in various ways to the physical strength of tissues, cell adhesion, and signal transduction (1-4).CS chains have a considerable structural variability, the biological functions of which are not well understood. The structure is an unbranched polymer linked through a unique tetrasaccharide (GlcUA-Gal-Gal-Xyl) to a serine residue in a PG and is composed of repeating disaccharides (-4GlcUA␤1-3GalNAc␤1-) n , which can be modified by O-sulfation reactions at various positions, where GlcUA and GalNAc represent *

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Section: Tablementioning

confidence: 64%

mentioning

confidence: 99%

Two Related but Distinct Chondroitin Sulfate Mimetope Octasaccharide Sequences Recognized by Monoclonal Antibody WF6

Pothacharoen

Kalayanamitra

Deepa

et al. 2007

Journal of Biological Chemistry

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“…More sophisticated determination of chondroitin sulphate (CS) epitope WF6 was also done in both OA and rheumatoid arthritis patients. However, as the levels of both HA and WF6 were elevated in patients with these two diseases, a strict correlation with disease activity was not fully validated [116]. As the involvement of bone tissue was also becoming recognised in the initiation and/or progression of OA, biochemical markers of bone turnover were also determined in some clinical studies.…”

Section: Bone Markers In Oamentioning

confidence: 99%

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Tat

Lajeunesse

Pelletier

et al. 2010

Best Practice & Research Clinical Rheumatology

156

121

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Over the past few decades, significant progress has been made with respect to new concepts about the pathogenesis of osteoarthritis (OA). This article summarises some of the knowledge we have today on the involvement of the subchondral bone in OA. It provides substantial evidence that changes in the metabolism of the subchondral bone are an integral part of the OA disease process and that these alterations are not merely secondary manifestations, but are part of a more active component of the disease. Thus, a strong rationale exists for therapeutic approaches that target subchondral bone resorption and/or formation, and data evaluating the drugs targeting bone remodelling raise the hope that new treatment options for OA may become available.

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“…Several factors are considered for the pathogenesis of kOA [6][7][8][9][10][11][12][13][14]. Complicated path biological interactions between the KallikreinKinin System (KKS), the Rennin-Angiotensin (RAS), angiogenesis and natural immunity could contribute to joint destruction in the disease process of kOA [15][16][17][18][19].…”

Section: Identification Of Circulating Natural Antibodies Against Endmentioning

confidence: 99%

Identification of Circulating Natural Antibodies against Endogenous Mediators in the Peripheral Blood Sera of Patients with Osteoarthritis of the Knee: A New Diagnostic Frontier

Savitskaya¹,

Duarte²,

Marin³

et al. 2012

J Mol Biomark Diagn

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Introduction: The presence of NA against EM regarding specificity and have gained increasing attention in proteome analysis for diagnosis, developing, monitoring and effective treatment of osteoarthritis of the knee (kOA). An understanding of the various regulatory systems controlling blood vessel growth, inflammation and pain in the join should lead to help explain kOA disease progression. To investigate the specific presence of NA (IgM, IgG, IgA) against EM (BK, AII, VEGF, bFGF) in the sera of kOA patients and control and to correlate this with process of joint destruction. Methods:In this study novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive ELISA method to directly detect immune complexes (NA-EM) in humans. Following this procedure, we examined variations in the levels of natural antibodies recognized a panel of self-antigens in the sera from healthy individuals and kOA patients. Blood samples were obtained from 250 patients with symptomatic kOA and 250 ages, sex-matched healthy individuals.Results: NA against EM was detected with novel ELISA assay in the sera of kOA patients as well as in the sera of control. At time of inclusion kOA patients (100%) had significantly higher BK-IgG levels relative to normal sera. The over expression BK-IgG were positively associated with destructive changes (KL>4; r=0.75; p<0.005). KOA patients in whom KL scores progress rapidly tend to have higher BK-IgG levels at all time point. Serum BK-IgG over expression in kOA patients were positively associated with destructive changes (KL>4; r=0.75; p<0.005). Elevated BK-IgG was significantly correlated with VAS (r=0.85; p<0.0001) and loss of functions (r=0.69; p<0.0003) in kOA patients. Affinity chromatography yielded EM-specific NA from the sera of healthy individuals and kOA patients. Conclusions:We showed that EM represents a group of novel self-antigens which are targeted by NA from kOA patients. Circulating BK-IgG in the sera has been proposed as a sensitive and specific marker of diagnosing kOA at early stages of the disease. Our results have potential applications for controlling unwanted angiogenesis, inflammation, pain and future response to therapy in kOA patients. Osteoarthritis of the knee (kOA) can be a progressive disabling disease, which results from the pathological imbalance of degradative and reparative processes, with concomitant inflammatory changes [2]. The clinical features of kOA include pain, stiffness, reduced motion, swelling, crepitus, and deformity [3][4][5]. Journal of Molecular Biomarkers & DiagnosisSeveral factors are considered for the pathogenesis of kOA [6][7][8][9][10][11][12][13][14]. Complicated path biological interactions between the KallikreinKinin System (KKS), the Rennin-Angiotensin (RAS), angiogenesis and natural immunity could contribute to joint destruction in the disease process of kOA [15][16][17][18][19]. It is also likely that biomarkers will be used in conjunction with imaging in order to establish stage of disease,...

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Raised chondroitin sulfate epitopes and hyaluronan in serum from rheumatoid arthritis and osteoarthritis patients

Cited by 35 publications

References 14 publications

Two Related but Distinct Chondroitin Sulfate Mimetope Octasaccharide Sequences Recognized by Monoclonal Antibody WF6

Two Related but Distinct Chondroitin Sulfate Mimetope Octasaccharide Sequences Recognized by Monoclonal Antibody WF6

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Identification of Circulating Natural Antibodies against Endogenous Mediators in the Peripheral Blood Sera of Patients with Osteoarthritis of the Knee: A New Diagnostic Frontier

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