Background/Purpose:  The regulation of Ca²⁺ entry by targeting a store-operated calcium release-activated channel (CRAC), known as ORAI, has shown benefits in the treatment of rheumatoid arthritis (RA). This study was undertaken to investigate the feasibility and efficiency of CRAC inhibitors in the treatment of RA.

Methods:  Peripheral T cells and B cells were obtained from RA patients and health donors. We engrafted pannus tissue from synovia, articular cartilage, bone, and peripheral blood mononuclear cells from RA patients who underwent prosthetic replacement arthroplasty for therapeutic purposes into NOD/ShiJic-scid mice (SCID-HuRAg mice) and treated them with CRAC inhibitors, including YM-58483, a specific short hairpin RNA and a monoclonal neutralizing antibody.

Results:  The treatment of CRAC inhibitors suppressed the Ca²⁺ entry and the activation in peripheral cells. CRAC inhibitors declined the production of human IgG2 and IgM in SCID-HuRAg mice. According to the results of histological evaluation, treatment of SCID-HuRAg mice with CRAC inhibitors markedly suppressed invasion of synovial tissue into cartilage. A decrease in mature osteoclast activity was also observed in CRAC inhibitor-treated SCID-HuRAg mice.

Conclusion:  These results indicate that the regulation of Ca²⁺ entry through CRAC channel is beneficial in the treatment of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-efficiency-of-the-regulation-of-ca2-entry-through-calcium-release-activated-calcium-channel-in-the-treatment-of-rheumatoid-arthritis/