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  • 1
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 208, No. 1_Supplement ( 2022-05-01), p. 104.08-104.08
    Abstract: Several lines of evidence suggest that the pathobiont Porphyromonas gingivalis is involved in the development and/or progression of rheumatoid arthritis. This bacterium produces cysteine proteases, such as gingipain RgpA, endowed with the potential to induce significant inflammation in patients with periodontitis and rheumatoid arthritis. Both diseases involve chronic inflammation with the production of pro-inflammatory cytokines, connective tissue breakdown and bone erosion. Methods A 25-peptide named BR1 from Porphyromonas gingivalis was synthesized for the study. Serum samples from patients with RA, early arthritis, other rheumatic diseases, and normal controls were used in the study. A monoclonal antibody named BR2mAb was derived from BALB/c mice immunized with the 25-mer peptide was produced as the control. Anti-BR1, ACPA and RF were detected by ELISA. Results Anti-BR1 were detected in 56.0% (59/106) of RA patients and were found in 63.8% (23/36) of RA patients without both RF and/or ACPA. The serological positive rates with the two tests of RF and ACPA and with the three tests of anti-BR1, RF, and ACPA were 66% and 84.2%, respectively. Anti-BR1 were detected in 60.0% (9/15) of patients with early arthritis, but neither RF nor ACPA was detected in this group of patients. The sensitivity and specificity for RA were 60.1% and 95%, respectively. The BR2 mAb reacted to Porphyromonas gingivalis as well. Conclusions A specific 25-mer peptide from the cysteine protease of P. gingivalis is the epitope for humoral immune response in rheumatoid arthritis. The anti-25-mer peptide antibody test is an excellent new test for the diagnosis of patients with RA and early arthritis. This study was supported by grants from the Ministry of Science and Technology, Taiwan (MOST-104-2314-B-039-045, MOST-105-2911-I-039-504, MOST-105-2314-B-039-047, MOST-106-2911-I-039-501, MOST-107-2314-B-039-050, MOST-108-2314-B-039-019), and from China Medical University Hospital (DMR-106-188, DMR-108-183, DMR-109-206).
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2022
    detail.hit.zdb_id: 1475085-5
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  • 2
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 210, No. 1_Supplement ( 2023-05-01), p. 85.12-85.12
    Abstract: The use of biological diseases-modifying anti-rheumatic drugs (bDAMRD) including anti-tumor necrosis factor-α (TNF-α) has revolutionized the therapy of rheumatoid arthritis (RA). However, approximately 30–40% of patients with RA do not response to anti-TNF therapy when used as the first-line bDMARD. Objective: The aim of the study is to develop a new, novel monoclonal antibody for the therapy of RA. Methods: Monoclonal antibody development: BALB/c mice were immunized with OVA-conjugated peptide for CIA. Spleen cells were collected for fusion with myeloma cells. The rats were divided into 6 groups: Normal control, CIA, IgG1(15 mg/kg)-treated CIA, low-mAb (3 mg/kg)-treated CIA, High-mAb (9 mg/kg)-treated CIA, and Enbrel (4.5 mg/kg)-treated CIA. Results: The monoclonal is only reacted to the immunized peptide and is IgG1 Kappa, high melting temperature with Tm=4.8, High binding to FCγRIIb and FCγR III, and low dissociation constant (Kd=19.6×10 −9) of Ag-mAb affinity. The mAb stains mainly on cytoplasm with several coarse discrete dots on SW982 cells. After treatment with this mAb in CIA, the mice have showed dose-dependent effects, improving articular index and ankle circumference, reduced inflammation and synovium proliferation, restored joint space narrowing, and cartilage on immunohistochemistry. The therapeutic results in the mAb-treated group has shown to be excellent in CIA animal RA model. Conclusion: We’ve generated a novel monoclonal antibody which has excellent therapeutic effects in the therapy of RA animal model. This study is the first time to demonstrate that targeting on the different signal pathway of CIA can have a promising effect on RA therapy.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2023
    detail.hit.zdb_id: 1475085-5
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  • 3
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 236.18-236.18
    Abstract: Impaired clearance of apoptotic cells (efferocytosis) plays an important role in the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE). Hydroxychloroquine (HCQ) has been widely used to treat autoimmune diseases. We aimed to investigate the underlying mechanism of efferocytosis in the action of HCQ. Methods Eighteen 6-week-old female BALB/c mice were treated Intraperitoneally with pristine in Pristine-induced lupus mice (PIL). Efferocytosis was performed using mouse cell lines EL4 as apoptotic cells and co-cultured with RAW 264.7 and peritoneal macrophages of PIL to investigate the effect of HCQ on efferocytosis which was analyzed with fluorescent microscopy and flow cytometry. Real time PCR was performed to investigate molecular mRNA expressions of signalling pathways. Protein level was measured by ELISA. Results HCQ could enhance efferocytosis with dose-dependent manner in both RAW264.7 cell lines and peritoneal macrophages of PIL with increased expression of GAS6 and MFG-E8 signallings. Both Gas6/Axl and MFG-E8/TG2 Signalling pathways play important roles in HCQ-enhanced efferocytosis. In HCQ-treated mice of PIL, HCQ reduced of IL-6 (p & lt;0.0036) and TNF-α (p & lt;0.06) protein levels in their ascites. Conclusions Our study shows that HCQ can enhance efferocytosis through both Gas6/Axl and MFG-E8/TG2 Signalling pathways and suppress the production of IL-6 and TNF-α. Our findings provide novel insights into understanding the mechanisms of HCQ, which could have the long-term beneficial effects on the therapy of SLE.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2020
    detail.hit.zdb_id: 1475085-5
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  • 4
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2020
    In:  Arthritis Research & Therapy Vol. 22, No. 1 ( 2020-12)
    In: Arthritis Research & Therapy, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2020-12)
    Abstract: Several lines of evidence suggest that the pathobiont Porphyromonas gingivalis is involved in the development and/or progression of auto-inflammatory diseases. This bacterium produces cysteine proteases, such as gingipain RgpA, endowed with the potential to induce significant bone loss in model systems and in patients. Objective We sought to gain further insight into the role of this pathobiont in rheumatoid arthritis (RA) and to identify novel therapeutic targets for auto-inflammatory diseases. Methods We profiled the antibody response to RgPA-specific domains in patient sera. We also tested the potential protective effects of RgpA domains in an experimental arthritis model. Results Pre-immunization of rats with purified recombinant RgpA domains alleviated arthritis in the joints of the rodents and reduced bone erosion. Using a functional genomics approach at both the mRNA and protein levels, we report that the pre-immunizations reduced arthritis severity by impacting a matrix metalloprotease characteristic of articular injury, a chemokine known to be involved in recruiting inflammatory cells, and three inflammatory cytokines. Finally, we identified an amino acid motif in the RgpA catalytic domain of P. gingivalis that shares sequence homology with type II collagen. Conclusion We conclude that pre-immunization against gingipain domains can reduce the severity of experimentally induced arthritis. We suggest that targeting gingipain domains by pre-immunization, or, possibly, by small-molecule inhibitors, could reduce the potential of P. gingivalis to translocate to remote tissues and instigate and/or exacerbate pathology in RA, but also in other chronic inflammatory diseases.
    Type of Medium: Online Resource
    ISSN: 1478-6362
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041668-4
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