Raised levels of anti-glucose-6-phosphate isomerase IgG in serum and synovial fluid from patients with inflammatory arthritis

Schaller, Monica; Stohl, William; Tan, Soon-Min; Benoit, Vivian M.; Hilbert, David M.; Ditzel, Henrik J.

doi:10.1136/ard.2004.025502

Cited by 41 publications

(29 citation statements)

References 47 publications

(58 reference statements)

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“…In the affected mice, mast cells are located at the invasive front of the pannus (9 ), which parallels the histopathology of patients with RA (10 ). Although these findings indicate that this antigen-antibody system could underlie the pathology of erosive joint inflammation in RA, there have been conflicting reports on the presence of anti-GPI antibodies in patients (11,12 ). Antibodies against cyclic citrullinated peptide and their target fillagrin, a component of connective tissue in the skin and cartilage, have also been linked to the pathogenesis of human RA, conceivably playing a role similar to that of anti-GPI in the KRN mouse (13 ).…”

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confidence: 86%

Increased Concentrations of Antibody-Bound Circulatory Cell-Free DNA in Rheumatoid Arthritis

et al. 2007

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Background: Increased concentrations of cell-free DNA have been found in several disorders and have been interpreted as evidence of increased rates of cell death or turnover. Evidence from in vitro and animal experiments suggests that DNA may play a role in the pathogenesis of rheumatoid arthritis (RA). Methods: We measured cell-free DNA in plasma and serum from patients with RA and healthy controls by use of quantitative PCR for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA. We used protein G Sepharose TM bead adsorption of plasma and elution to isolate antibody-bound DNA. Results: In paired plasma and serum samples of 16 healthy controls the median GAPDH copies were 4500 genome equivalents (GE)/mL plasma (range 319 -21 000) and in 26 RA patients 17 000 GE/mL plasma (2100 -2 375 000, P ‫؍‬ 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700 -239 000) and from RA patients 222 000 GE/mL (21 000 -2 375 000, P ‫؍‬ 0.004). A median of 81% of the cell-free DNA in RA was associated with antibody compared with 9% in healthy controls (P ‫؍‬ 0.001). The concentrations of DNA did not vary with the type of therapy patients received.

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confidence: 86%

Increased Concentrations of Antibody-Bound Circulatory Cell-Free DNA in Rheumatoid Arthritis

et al. 2007

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“…Several of these autoantibodies have emerged as potential arthritogenic factors. For example, anti-glucose-6 phosphate isomerase and anti-type II collagen antibodies, both of which are highly arthritogenic in mice, can be detected in patients with RA (Schaller et al, 2005;Mullazehi et al, 2007). In addition, anticitrullinated protein autoantibodies, the most prevalent in RA, can bind citrullinated fibrinogen in RA joints to form immune complexes (Zhao et al, 2008), which stimulate macrophages to produce inflammatory cytokines such as TNF␣ (Clavel et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

RN486, a Selective Bruton's Tyrosine Kinase Inhibitor, Abrogates Immune Hypersensitivity Responses and Arthritis in Rodents

Kim²,

Postelnek³

et al. 2012

J Pharmacol Exp Ther

130

119

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Genetic mutation and pharmacological inhibition of Bruton's tyrosine kinase (Btk) both have been shown to prevent the development of collagen-induced arthritis (CIA) in mice, providing a rationale for the development of Btk inhibitors for treating rheumatoid arthritis (RA). In the present study, we characterized a novel Btk inhibitor, 6-cyclopro-, in vitro and in rodent models of immune hypersensitivity and arthritis. We demonstrated that RN486 not only potently and selectively inhibited the Btk enzyme, but also displayed functional activities in human cell-based assays in multiple cell types, blocking Fc receptor cross-linking-induced degranulation in mast cells (IC 50 ϭ 2.9 nM), Fc␥ receptor engagement-mediated tumor necrosis factor ␣ production in monocytes (IC 50 ϭ 7.0 nM), and B cell antigen receptor-induced expression of an activation marker, CD69, in B cells in whole blood (IC 50 ϭ 21.0 nM). RN486 displayed similar functional activities in rodent models, effectively preventing type I and type III hypersensitivity responses. More importantly, RN486 produced robust anti-inflammatory and boneprotective effects in mouse CIA and rat adjuvant-induced arthritis (AIA) models. In the AIA model, RN486 inhibited both joint and systemic inflammation either alone or in combination with methotrexate, reducing both paw swelling and inflammatory markers in the blood. Together, our findings not only demonstrate that Btk plays an essential and conserved role in regulating immunoreceptor-mediated immune responses in both humans and rodents, but also provide evidence and mechanistic insights to support the development of selective Btk inhibitors as small-molecule disease-modifying drugs for RA and potentially other autoimmune diseases.

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“…Matsumoto et al demonstrated that anti-G6PI Abs produced in K/BxNT cell receptor transgenic mice was arthritogenic when it was injected into normal mice [5]. Later, although Schaller et al demonstrated an increase of anti-G6PI Abs in most of RA patients, they also found that anti-G6PI Abs were not unique to patients with RA but were present in many patients with inflammatory arthritis, suggesting the unspecificity of anti-G6PI Abs for RA patients [7,8]. Matsumoto et al also reported the low prevalance of anti-G6PI Abs in patients with RA [13].…”

Section: Discussionmentioning

confidence: 99%

“…Later, Schaller et al demonstrated that increasing of anti-G6PI Abs in most of RA patients, suggested a linkage between animal model and human RA [6]. However, they also found that anti-G6PI Abs were not unique to patients with RA but were present in many patients with inflammatory arthritis, proposing a notion that immunebased inflammatory arthritis induces increases of anti-G6PI Abs and G6PI/anti-G6PI immune complexes, which in turn influence proinflammatory cytokines release and involve in the development of inflammatory arthritis [7,8] serum G6PI alone or in combination with anti-cyclic citrullinated peptide Abs (anti-CCP Abs) may improve the clinical diagnosis of RA [9].…”

Section: Introductionmentioning

confidence: 99%

The diagnostic significance of glucose-6-phosphate isomerase (G6PI) antigen and anti-G6PI antibody in rheumatoid arthritis patients

Yang¹,

Ge²,

Dong³

et al. 2013

ABB

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Objective: To investigate whether glucose-6-phosphate isomerase (G6PI) antigen and anti-G6PI antibodies could be applied for the clinical diagnostic markers of rheumatoid arthritis (RA) and its associations with RA activity states. Methods: The levels of G6PI antigens and anti-G6PI Abs in sera from 176 RA patients in different states, 35 non-RA patients and 100 healthy donors and in synovia fluids from 33 patients and 11 non-RA patients were measured by ELISA. Results: The sensitivity and specificity of G6PI antigens in the RA patients were 75.0% and 93.3%, respectively. The levels of serum G6PI antigens in 176 RA patients were significantly higher than non-RA patients and the health controls. Especially, there was a significant difference between the active phase and the inactive phase in G6PI antigens levels. The levels of G6PI antigens in synovia fluid were also significantly higher in RA groups than in non-RA patients. With the values of the anti-G6PI Abs in sera, there were no marked differences among RA, non-RA patients and health controls. Also, there was no significant difference between the active phase and the inactive phase in RA patients. However, there were no significant differences of G6PI and anti-G6PI between RA patients and health controls in synovial fluid. Conclusions: G6PI is highly correlated with the activity states of RA, and could be applied for a clinical biomarker with high sensitivity and specificity for the diagnosis of RA.

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Raised levels of anti-glucose-6-phosphate isomerase IgG in serum and synovial fluid from patients with inflammatory arthritis

Cited by 41 publications

References 47 publications

Increased Concentrations of Antibody-Bound Circulatory Cell-Free DNA in Rheumatoid Arthritis

Increased Concentrations of Antibody-Bound Circulatory Cell-Free DNA in Rheumatoid Arthritis

RN486, a Selective Bruton's Tyrosine Kinase Inhibitor, Abrogates Immune Hypersensitivity Responses and Arthritis in Rodents

The diagnostic significance of glucose-6-phosphate isomerase (G6PI) antigen and anti-G6PI antibody in rheumatoid arthritis patients

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