Exploiting CD22 To Selectively Tolerize Autoantibody Producing B-Cells in Rheumatoid Arthritis
| العنوان: | Exploiting CD22 To Selectively Tolerize Autoantibody Producing B-Cells in Rheumatoid Arthritis |
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| المؤلفون: | Kyle J. Bednar, Tadimeti S. Rao, Wai-Ping Fung-Leung, Matthew S. Macauley, Corwin M. Nycholat, James C. Paulson |
| المصدر: | ACS Chemical Biology. 14:644-654 |
| بيانات النشر: | American Chemical Society (ACS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | musculoskeletal diseases, 0301 basic medicine, Sialic Acid Binding Ig-like Lectin 2, Monophosphoryl Lipid A, 01 natural sciences, Biochemistry, Article, Arthritis, Rheumatoid, Mice, 03 medical and health sciences, chemistry.chemical_compound, Antigen, immune system diseases, medicine, Citrulline, Animals, Humans, skin and connective tissue diseases, B-cell activating factor, Autoantibodies, Autoimmune disease, B-Lymphocytes, 010405 organic chemistry, business.industry, CD22, Autoantibody, General Medicine, medicine.disease, 0104 chemical sciences, 030104 developmental biology, chemistry, Case-Control Studies, Rheumatoid arthritis, Immunology, Molecular Medicine, business, Immunologic Memory |
| الوصف: | Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects the synovial joints and can lead to bone erosion and cartilage damage. One hallmark of RA is anti-citrullinated protein autoantibodies (ACPA) and memory citrulline-specific B-cells, which have been implicated in RA pathogenesis. While depletion of B-cells with Rituximab improves clinical responses in RA patients, this treatment strategy leaves patients susceptible to infections. Therefore, using Siglec-engaging Tolerance-inducing Antigenic Liposomes (STALs) to selectively target the citrulline-specific B-cells may be beneficial. ACPA production from purified human RA patients’ B-cells in vitro was achieved through a set stimulation conditions, which includes: BAFF, anti-CD40, IL-21, and LPS. In vivo generation of citrulline specific B-cells and ACPA production was accomplished by antigenic liposomes consisting of monophosphoryl lipid A (MPLA) and a cyclic citrullinated peptide (CCP) administered to SJL/J mice. We show that STALs that co-display a high affinity CD22 glycan ligand and synthetic citrullinated antigen (CCP STALs) can prevent ACPA production from RA patients’ memory B-cells in vitro. These CCP STALs were also effective in inducing tolerance to citrullinated antigens in SJL/J mice. The results demonstrate that tolerization of the B-cells responsible for ACPA can be achieved by exploiting the inhibitory receptor CD22 with high affinity glycan ligands. Such a treatment strategy could be beneficial in the treatment of RA. |
| تدمد: | 1554-8937 1554-8929 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed233698323b0d19afa0066e4c8c8427Test https://doi.org/10.1021/acschembio.8b01018Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ed233698323b0d19afa0066e4c8c8427 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15548937 15548929 |
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