Immunogenicity of Anti-TNF-α Agents in Autoimmune Diseases

Aikawa, Nádia E.; Carvalho, Jozélio Freire de; Silva, Clóvis A.; Bonfá, Eloísa

doi:10.1007/s12016-009-8140-3

Cited by 176 publications

(111 citation statements)

References 41 publications

(86 reference statements)

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“…Several studies have suggested that the production of anti-TNF-α inhibitor antibodies is the main reason for treatment refractoriness (23)(24)(25). However, the frequency of the anti-etanercept antibody was reported at <5.6% (26)(27), considerably lower than that of other anti-TNF-α inhibitors (12-44% anti-infliximab and 6-87% anti-adalimumab) (28), and no correlation has been demonstrated between the presence of the anti-etanercept antibody and poor clinical response. In this study, we have shown that the production of anti-etanercept antibody by mice exposed to an etanercept overdose is associated with the inefficiency of the drug.…”

Section: Discussionmentioning

confidence: 99%

Induced production of anti-etanercept antibody in collagen-induced arthritis

Kim

Jung

et al. 2014

Molecular Medicine Reports

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Abstract. Etanercept is a widespread biological drug for the treatment of rheumatoid arthritis, which inhibits tumor necrosis factor-α (TNF-α). Recently, the presence of antibodies targeting TNF-α inhibitors such as infliximab and adalimumab, was reported. However, few reports have studied etanercept in a mouse model of arthritis. We investigated the induction of anti-etanercept antibody production, along with the antibody's potential interfering effects on the biological function of etanercept, in mice with collagen-induced arthritis (CIA). CIA mice received an intraperitoneal injection of etanercept (25, 100 or 400 µg per mouse). The degree of inflammation and cartilage erosion was evaluated, and the number of osteoclasts in the ankle joints was assessed by TRAP staining. The level of pro-inflammatory cytokines in the serum was measured. To analyze the anti-osteoporotic effect of etanercept, microfocal computed tomography analyses of femurs and tibias were performed. Etanercept treatment decreased both the incidence and severity of arthritis in a dose-dependent manner, except for the highest dose of 400 µg. The mice that were treated with 25 and 100 µg etanercept showed an improvement in inflammation, cartilage damage, and even bone loss. However, mice treated with 400 µg etanercept showed no significant improvement in any of the tested parameters. Using a customized enzyme-linked immunosorbent assay (ELISA), the presence of the anti-etanercept antibody was detected in the serum in this treatment-refractory group. The therapeutic effect of etanercept was reduced in the CIA mice that developed the anti-etanercept antibody. In conclusion, the production of an anti-etanercept antibody can be induced in CIA mice, and this antibody can considerably reduce the anti-arthritic and anti-osteoporotic effects of etanercept.

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Section: Discussionmentioning

confidence: 99%

Induced production of anti-etanercept antibody in collagen-induced arthritis

Kim

Jung

et al. 2014

Molecular Medicine Reports

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“…TNFα production is elevated in various auto-immune diseases such as rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease and psoriasi [40]. Thus, inhibition of the Mnk kinases may have potential therapeutic applications in the treatment of the above diseases.…”

Section: Introductionmentioning

confidence: 99%

Mnk kinases in cytokine signaling and regulation of cytokine responses

Joshi¹,

Platanias²

2012

Biomolecular Concepts

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The kinases Mnk1 and Mnk2 are activated downstream of the p38 MAPK and MEK/ERK signaling pathways. Extensive work over the years has shown that these kinases control phosphorylation of the eukaryotic initiation factor 4E (eIF4E) and regulate engagement of other effector elements, including hnRNPA1 and PSF. Mnk kinases are ubiquitously expressed and play critical roles in signaling for various cytokine receptors, while there is emerging evidence that they have important functions as mediators of pro-inflammatory cytokine production. In this review the mechanisms of activation of MNK pathways by cytokine receptors are addressed and their roles in diverse cytokine-dependent biological processes are reviewed. The clinical-translational implications of such work and the relevance of future development of specific MNK inhibitors for the treatment of malignancies and auto-immune disorders are discussed.

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“…In Russia, the approved drugs of this group for treating JIA are human monoclonal antibodies to TNF-α -adalimumab (from 4 years of age) and soluble receptors to TNF -etanercept (from 2 years of age) [15]. By binding with TNF-α, adalimumab prevents its interaction with the corresponding receptor; thus, it prevents development of the subsequent cytokine-mediated inflammation by reducing generation of interleukins (IL) 1 and 6, suppressing functional activity of neutrophils and eosinophils, restricting migration of leukocytes, expression of adhesion molecules and tissue degradation by aggressive synoviocytes and chondrocytes [16,17]. The drug's efficacy for JIA was proved in a trial by the Pediatric Rheumatology International Trials Organization (PRINTO) under the guidance of D.J.…”

mentioning

confidence: 99%