Therapeutic effects of anti-CD154 antibody in cynomolgus monkeys with advanced rheumatoid arthritis

Choi, Eung‐Chil; Lee, Kyo Won; Park, Hyojun; Kim, Hwajung; Lee, Jong Hyun; Song, Ji Woo; Yang, Jehoon; Kwon, Yeongbeen; Kim, Tae Min; Park, Jae Berm; Kim, Sungjoo

doi:10.1038/s41598-018-20566-z

Cited by 11 publications

(20 citation statements)

References 34 publications

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“…This suggests that the arthritis-resistant MHC allele may differ between species, even when they belong to the same genus. Previous studies have demonstrated CIA induction in M. fascicularis [6][7][8][9], however, there has been no evaluation of the genetic background of the Previous studies have demonstrated CIA induction in M. fascicularis, and have shown the therapeutic effects of IL-6 neutralizing agents in CIA [6,7,[16][17][18]. However, these studies did not use a standardized scoring system or conduct behavior and pain analysis, and did not evaluate bone mineral density.…”

Section: Discussionmentioning

confidence: 99%

“…These CIA models, based on M. mulatta, had only a 70% induction rate for arthritis [4]. The cynomolgus monkey, M. fascicularis, has emerged as an alternative primate animal model for RA [6][7][8][9], however, a standardized scoring system has not yet been established for this model. Furthermore, osteoporosis is one of the major comorbidities of RA [10], and an evaluation of the degree of osteoporosis, such as bone density in primates models of RA, has not been conducted previously.…”

Section: Journal Of Translational Medicinementioning

confidence: 99%

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The establishment of a rheumatoid arthritis primate model in Macaca fascicularis

Lee

Min

et al. 2020

J Transl Med

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Background: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that mostly affects the joints and leads to the destruction of cartilage. An RA model in non-human primates is especially useful because of their close phylogenetic relationship to humans in terms of cross-reactivity to compounds developed using modern drug technologies. Methods: We used a collagen-induced arthritis (CIA) model in Macaca fascicularis. CIA was induced by the immunization of chicken type II collagen. Swelling was measured as the longitudinal and transverse axes of 16 proximal interphalangeal joints. Results: A new system for visual evaluation was created, with a perfect score of 16. Individual behavioral analysis was also conducted. Serum was collected once a week after the first immunization. Blood chemistry and inflammatory cytokine parameters were higher in the CIA group than in the wild type group. Conclusion: In conclusion, we established CIA in M. fascicularis, and the results can be used for drug evaluation models.

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Section: Discussionmentioning

confidence: 99%

Section: Journal Of Translational Medicinementioning

confidence: 99%

The establishment of a rheumatoid arthritis primate model in Macaca fascicularis

Lee

Min

et al. 2020

J Transl Med

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show abstract

“…This suggests that the arthritis-resistant MHC allele may differ between species, even when they belong to the same genus. Previous studies have demonstrated CIA induction in M. fascicularis [6][7][8][9], however, there has been no evaluation of the genetic background of the arthritis-resistant MHC allele. The present study showed that the speci c MHC alleles known to play crucial roles in the induction of CIA in M. mulatta were not active in M. fascicularis.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The establishment of a rheumatoid arthritis primate model in Macaca fascicularis

Lee

Min

et al. 2020

Preprint

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Abstract Background: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that mostly affects the joints and leads to the destruction of cartilage. An RA model in non-human primates is especially useful because of their close phylogenetic relationship to humans in terms of cross-reactivity to compounds developed using modern drug technologies.Methods: We used a collagen-induced arthritis (CIA) model in Macaca fascicularis. CIA was induced by the immunization of chicken type II collagen. Swelling was measured as the longitudinal and transverse axes of 16 proximal interphalangeal joints. Results: A new system for visual evaluation was created, with a perfect score of 16. Individual behavioral analysis was also conducted. Serum was collected once a week after the first immunization. Blood chemistry and inflammatory cytokine parameters were higher in the CIA group than in the wild type group. Conclusion: In conclusion, we established CIA in M. fascicularis, and the results can be used for drug evaluation models.

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“…Both CD28-CD80/86 and CD154-CD40 interactions play an important role in B cell activation and proliferation, and CD154-CD40 ligation specifically provides key signaling for thymus-dependant humoral immunity responses, such as the isotype class-switching and affinity maturation required to generate high affinity anti-CII IgG autoantibodies [65][66][67]. Furthermore, previous research has demonstrated that the disruption of CD28-CD80/86 and CD154-CD40 interactions results in reduced anti-CII autoantibody titres, prevention of disease development, and/or amelioration of disease in CIA and other autoimmune arthritis models [68][69][70][71][72]. In other words, pro-inflammatory T cell development and activation is inhibited by BBR early, which leads to a later reduction in B cells reactive to CII stimulus, and this timing fits with classical T cell-mediated B cell activity.…”

Section: Discussionmentioning

confidence: 99%

Berberine delays onset of collagen induced arthritis through T cell suppression

Vita¹,

Lyons²,

Aljobaily³

et al. 2019

Preprint

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RUNNING TITLE (less than 50 characters): Berberine delays onset of collagen arthritis model KEY WORDS (5 words not in the title): CIA, berberine, RA, autoimmune, T cell ABSTRACT (250 words or less): Previous evidence suggests that berberine (BBR), a clinically relevant plant-derived alkaloid, alleviates symptoms of clinically apparent collagen induced arthritis (CIA), and may have a prophylactic role from in vitro studies. Thus, we used a CIA model to determine if BBR merits further exploration as a prophylactic treatment for rheumatoid arthritis. Mice were treated with either 1 mg/kg/day of BBR or a vehicle (PBS) control via IP injections from day 0 to day 28, were left untreated (CIA control), or were in a non-arthritic control group. Incidence of arthritis in BBR mice was 40%, compared to 90% in the CIA and 80% in the PBS controls. Populations of B cells and T cells from the spleens and draining lymph nodes were examined from mice across treatment groups on day 14 and from the remaining mice on day 28 when arthritic signs and symptoms were expected to be apparent. BBR-treated mice had significantly reduced populations of CD4 + T cells, CXCR5 + T fh cells, and an increased proportion of T reg at both day 14 and day 28 endpoints, as well as decreased CD28 + and CD154 + CD4 + T cells at day 14. BBR-treated mice also experienced a significant reduction of CD19 + B cells in LNs at day 28. Additionally, BBR treatment resulted in significantly lower anti-collagen type II-specific (anti-CII) IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement, and that its effect may be mediated through T cell suppression, which indirectly affects B cell activity. and PBS controls ( Fig. 2B). When comparing anti-CII IgG levels between arthritic and nonarthritic mice within the BBR group specifically, however, anti-CI IgG1, IgG2a and total IgG were all significantly reduced in the non-arthritic mice compared to those who developed arthritis (Fig. 2C). Additionally, there appeared to be a vehicle-specific effect on circulating anti-CII IgG in which the administration of PBS with 0.01% DMSO elicited elevated levels of anti-CII IgG1 and total IgG in vehicle control mice ( Fig. 2A-B).Key CD4 + T cell population characteristics in response to berberine treatment-On day 14, we observed a significant reduction in populations of both CD4 + T cells and CXCR5 + T fh cells in the LNs and spleen of BBR-treated mice (Fig. 3A-B), as well as a reduction in the percentage of CD28 + and CD154 + CD4 + T cells in the spleen and LNs of BBR-treated mice (Fig. 3A-B). By the day 28 experimental endpoint we continued to observe a significant reduction in CD4 + T cells and CXCR5 + T fh cells in the spleen and LNs of BBR-treated mice ( Fig. 3C-D), however, there was no significant difference in the percentage of CD28 + and CD154 + CD4 + T cells between treatment groups (Fig 3C-D). Berberine treatment leads to increased proportion of FOXP3 + CD25 + CD4 + T cells-To examineBBRs effect on ...

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Therapeutic effects of anti-CD154 antibody in cynomolgus monkeys with advanced rheumatoid arthritis

Cited by 11 publications

References 34 publications

The establishment of a rheumatoid arthritis primate model in Macaca fascicularis

The establishment of a rheumatoid arthritis primate model in Macaca fascicularis

The establishment of a rheumatoid arthritis primate model in Macaca fascicularis

Berberine delays onset of collagen induced arthritis through T cell suppression

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