scholarly journals The establishment of a rheumatoid arthritis primate model in Macaca fascicularis

2020 ◽  
Author(s):  
Hyun Sik Na ◽  
Seon-young Lee ◽  
Hong Ki Min ◽  
Wan-je Park ◽  
Jung-hwan Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Evaluation ◽  
Autoimmune Disorder ◽  
Type Ii Collagen ◽  
Blood Chemistry ◽  
Cross Reactivity ◽  
Visual Evaluation ◽  
Primate Model ◽  
Cynomolgus Monkeys ◽  
Close Phylogenetic Relationship

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 cynomolgus monkeys. 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 cynomolgus monkeys, and the results can be used for drug evaluation models.

scholarly journals The establishment of a rheumatoid arthritis primate model in Macaca fascicularis

2020 ◽  
Author(s):  
Hyun Sik Na ◽  
Seon-young Lee ◽  
Hong Ki Min ◽  
Wan-je Park ◽  
Jung-hwan Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Macaca Fascicularis ◽  
Drug Evaluation ◽  
Autoimmune Disorder ◽  
Type Ii Collagen ◽  
Blood Chemistry ◽  
Cross Reactivity ◽  
Visual Evaluation ◽  
Primate Model ◽  
Close Phylogenetic Relationship

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.

scholarly journals REVERSE TRANSLATION OF HUMAN BIO-AGING MEASURES TO CYNOMOLGUS MONKEYS TO TEST ASSOCIATIONS WITH DOMINANCE RANK

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S349-S349
Author(s):  
Noah Snyder-Mackler ◽  
Carol Shively ◽  
Tom Register ◽  
Daniel W Belsky
Keyword(s):  
Social Status ◽  
Dominance Rank ◽  
Blood Chemistry ◽  
Experimental Manipulation ◽  
Biological Aging ◽  
Primate Model ◽  
Cynomolgus Monkeys ◽  
Health Decline ◽  
Using Data ◽  
Human Primate

Abstract Social status is a powerful correlate of aging-related health decline. Observational data in humans suggest that disadvantaged social status may be associated with accelerated biological aging. But establishing causality in this relationship poses challenges; experimental manipulation of human social status is not possible. In contrast, social status can be experimentally manipulated non-human primates (e.g. Snyder-Mackler 2016 Science). We conducted analysis to reverse-translate blood-chemistry of biological aging to cynomolgus monkeys using data from several hundred animals in the Wake Primate Center breeding colony. We are applying these measures in an independent sample of monkeys with ascertained dominance rank to test replication in the non-human primate model of the human social gradient in biological aging. Parallel analysis of DNA methylation-based measures of biological aging are ongoing and should be available to present by Fall 2019. Results will inform potential to use this non-human primate model to study social determinants of biological aging.

Multiple antibody reactivities to citrullinated antigens in sera from patients with rheumatoid arthritis: association with HLA-DRB1 alleles

2008 ◽  
Vol 68 (5) ◽  
pp. 736-743 ◽  
Author(s):  
O Snir ◽  
M Widhe ◽  
C von Spee ◽  
J Lindberg ◽  
L Padyukov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Shared Epitope ◽  
Type Ii Collagen ◽  
Cross Reactivity ◽  
Igg Antibodies ◽  
Serum Samples ◽  
Hla Dr ◽  
Citrullinated Proteins ◽  
The Relationship ◽  
Citrullinated Protein

Background:Autoantibodies to cyclic citrullinated peptides (anti-CCP) are present in most patients with rheumatoid arthritis (RA), and associate with HLA-DRB1 shared epitope (SE) alleles.Objective:To investigate reactivities of anti-CCP to various citrullinated proteins/peptides, which represent potential autoantigens in RA, and to examine the relationship between such antibodies, and their association with genetic variants within HLA-DRB1 SE alleles.Methods:Serum samples from 291 patients with established RA and 100 sex- and age-matched healthy subjects were included in this study. Sera were first analysed for presence of anti-CCP antibodies and further for IgG and IgA antibodies towards candidate autoantigens in both their native and citrullinated form including: fibrinogen, α-enolase peptide-1 and the C1-epitope of type II collagen (C1III). Antibody specificity was confirmed by cross-reactivity tests. HLA-DR genotyping was performed.Results:72% of patients with RA were anti-CCP positive. Among the candidate autoantigens examined, IgG antibodies to citrullinated fibrinogen were found in 66% of patients’ sera and in 41% for both citrullinated α-enolase peptide-1 and citrullinated C1III. These antibodies were mainly seen in the anti-CCP-positive patient group; they were specific for their respective antigen and displayed limited cross reactivity. IgA responses were also detected, but less frequently than IgG. Anti-CCP and anti-citrullinated protein antibodies were associated with HLA-DRB1*04 rather than with HLA-DRB1*01 alleles.Conclusions:Antibodies directed against several citrullinated antigens are present in CCP-positive RA, with many patients displaying multireactivity. All specific reactivities were primarily associated with the HLA-DRB1*04 alleles, suggesting common pathways of anti-citrulline immunity.

Hexachlorobenzene toxicity in the monkey ovary: III. Ultrastructure induced by high (10 mg/kg) dose exposure

1991 ◽  
Vol 49 ◽  
pp. 130-131
Author(s):  
A. Singh ◽  
A. Dykeman ◽  
J. Jarrelf ◽  
D. C. Villeneuve
Keyword(s):  
Present Report ◽  
Reproductive Toxicity ◽  
Control Group ◽  
Primate Model ◽  
Human Follicular Fluid ◽  
Thin Sections ◽  
Cynomolgus Monkeys ◽  
Cacodylate Buffer ◽  
Induction Cycle ◽  
Comprehensive Study

Hexachlorobenzene (HCB), a persistent and mobile organochlorine pesticide, occurs in environment. HCB has been shown to be present in human follicular fluid. An objective of the present report, which is part of a comprehensive study on reproductive toxicity of HCB, was to determine the cytologic effects of the compound on ovarian follicles in a primate model.Materials and Methods. Eight Cynomolgus monkeys were housed under controlled conditions at Animal facility of Health and Welfare, Ottawa. Animals were orally administered gelatin capsules containing HCB mixed with glucose in daily dosages of 0.0 or 10 mg/kg b.w. for 90 days; the former was the control group. On the menstrual period following completion of dosing, the monkeys underwent an induction cycle of superovulation. At necropsy, one-half of an ovary from each animal was diced into ca. 2- to 3-mm cubed specimens that were fixed by immersion in 2.5% glutaraldehyde in 0.1 M cacodylate buffer (pH 7.3). Subsequent procedures followed to obtain thin sections that were examined in a Hitachi H-7000 electron microscope have been described earlier.

scholarly journals FRI0596 NOVEL AUTOANTIBODY BIOMARKERS FOR THE PREDICTION OF THERAPY RESPONSE IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 904.1-904
Author(s):  
P. Vandormael ◽  
A. Pues ◽  
E. Sleurs ◽  
P. Verschueren ◽  
V. Somers
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapy Response ◽  
Autoimmune Disorder ◽  
First Line ◽  
Research Support ◽  
Serum Samples ◽  
Glucocorticoid Treatment ◽  
Baseline Serum ◽  
Disease Remission ◽  
Antibody Reactivity

Background:Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by chronic inflammation of the joint synovium and presence of autoantibodies in most patients. For RA, many treatments are currently available but each treatment will only induce disease remission in a subset of patients. Moreover, finding out which patients respond well to first-line therapy with classical synthetic disease modifying anti-rheumatic drugs (csDMARDs), still largely depends on trial and error.Objectives:In this study, we aim to find novel RA autoantibody biomarkers that predict therapy response to csDMARDs before the initiation of treatment.Methods:In the CareRA trial, a Flemish multicenter study of different treatment regimes, serum samples were collected from RA patients that did or did not show disease remission (DAS28(CRP)<2.6) in response to csDMARDs, combined with a step down glucocorticoid treatment. In our study, baseline samples, collected before the start of treatment, were used to determine predictive antibody reactivity. A cDNA phage display library, representing the antigens from RA synovial tissue, was constructed and screened for antibody reactivity in baseline serum samples of RA patients that failed to reach remission at week 16. Using enzyme-linked immunosorbent assays (ELISA), antibody reactivity against the identified antigens was initially determined in pooled baseline serum samples of RA patients that did (n=50) or did not (n=40) reach disease remission at week 16. Antigenic targets that showed increased antibody reactivity in pools from patients that did not reach disease remission, were further validated in individual serum samples of 69 RA patients that did not reach DAS28(CRP) remission at week 16, and 122 RA patients that did.Results:Screening and validation of antibody reactivity resulted in 41 novel antigens. The retrieved antigenic sequences correspond to (parts of) known proteins and to randomly formed peptides. A panel of 3 of these peptide antigens could be composed, whose baseline antibody reactivity correlated with lack of therapy response at week 16. Presence of antibodies against at least one of these 3 antigens was significantly higher in individual samples of RA patients that did not reach DAS28(CRP) remission (43 vs. 29%, p=0.041), or that failed to reach ACR 70 (42 vs. 26%, p=0.029) response criteria at week 16, compared to RA patients that did reach these respective criteria. In addition, RA patients which were positive for this antibody panel at baseline, also showed less DAS(CRP) remission at week 4 and week 8.Conclusion:We have identified a set of 3 antibody biomarkers that can predict failure of early disease remission after first-line RA therapy, which might contribute to personalized medicine decisions.Disclosure of Interests:Patrick Vandormael: None declared, Astrid Pues: None declared, Ellen Sleurs: None declared, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies, Veerle Somers Grant/research support from: Research grant from Pfizer and BMS

scholarly journals Probiotics and Amelioration of Rheumatoid Arthritis: Significant Roles of Lactobacillus casei and Lactobacillus acidophilus

2021 ◽  
Vol 9 (5) ◽  
pp. 1070
Author(s):  
Alok K. Paul ◽  
Anita Paul ◽  
Rownak Jahan ◽  
Khoshnur Jannat ◽  
Tohmina A. Bondhon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Air Pollution ◽  
Lactobacillus Acidophilus ◽  
Lactobacillus Casei ◽  
Autoimmune Disorder ◽  
Cartilage Degradation ◽  
Preclinical Studies ◽  
Gastrointestinal Microbiota ◽  
Specific Factors ◽  
Lactobacillus Spp

Rheumatoid arthritis is a chronic autoimmune disorder that can lead to disability conditions with swollen joints, pain, stiffness, cartilage degradation, and osteoporosis. Genetic, epigenetic, sex-specific factors, smoking, air pollution, food, oral hygiene, periodontitis, Prevotella, and imbalance in the gastrointestinal microbiota are possible sources of the initiation or progression of rheumatoid arthritis, although the detailed mechanisms still need to be elucidated. Probiotics containing Lactobacillus spp. are commonly used as alleviating agents or food supplements to manage diarrhea, dysentery, develop immunity, and maintain general health. The mechanism of action of Lactobacillus spp. against rheumatoid arthritis is still not clearly known to date. In this narrative review, we recapitulate the findings of recent studies to understand the overall pathogenesis of rheumatoid arthritis and the roles of probiotics, particularly L. casei or L. acidophilus, in the management of rheumatoid arthritis in clinical and preclinical studies.

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