ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 80

The Role of Adopter Protein SH3BP2 in a Murine Systemic Lupus Erythematosus Model

Kyoko Kawahara1, Tomoyuki Mukai 2, Akiko Nagasu 1, Masanori Iseki 3, Hajime Nagasu 4, Shoko Tshuji 1, Takahiko Akagi 1, Yasuyoshi Ueki 5 and Yoshitaka Morita 1, 1Department of Rheumatology, Kawasaki medical School, Kurashiki, Okayama, Japan, 2Department of Rheumatology, Kawasaki medical School, Kurashiki, Okayama, Okayama, Japan, 3Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki, Okayama, Japan, 4Department of Nephrology and Hypertension, Kawasaki medical School, Kurashiki, Okayama, Japan, 5Department of Biomedical Sciences and Comprehensive Care Indiana University School of Dentistry, Indianapolis, IN

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: , , ,

Session Information

Date: Sunday, November 10, 2019

Title: SLE – Animal Models Poster

Session Type: Poster Session (Sunday)

Session Time: 9:00AM-11:00AM

Background/Purpose: An adaptor protein SH3BP2 (Src homology 3 domain-binding protein 2) is widely expressed in immune cells and controls intracellular signaling pathways, such as Syk, Src, Vav, and PLCγ. In previous reports, SH3BP2 has been reported to regulate the production of antibodies in B cells. We have previously reported that, in a collagen-induced arthritis model, SH3BP2 loss-of-function mutation suppresses antibody production against type II collagen and markedly prevents the development of arthritis (Mukai T, et al. Arthritis Rheumatol 2015). To further investigate the role of SH3BP2 in autoimmune diseases, we examine the effect of SH3BP2 deficiency in a murine systemic lupus erythematosus (SLE) model.

Methods: For the lupus model, we used Faslpr mice (C57BL6 background), which possess impaired Fas signaling. SH3BP2-deficient mice and Faslpr mice were crossed to create SH3BP2-deficient Faslpr double mutant mice. These mice were observed until 35-week old, and then serum, urine, spleen, inguinal lymph nodes, kidney and bone marrow samples were collected. We evaluated proteinuria, splenomegaly, serum anti-dsDNA antibody titer, and histological renal damage. In addition, we analyzed B- and T-cell subsets by flow cytometry.

Results: Wild-type, SH3BP2-deficient, Faslpr, and SH3BP2-deficient Faslpr double mutant mice were analyzed. Faslpr mice exhibited splenomegaly, proliferative glomerulus lesions, and increased anti-dsDNA antibody levels compared to wild-type and Faslpr mice. All of them were significantly ameliorated by SH3BP2 deficiency. Furthermore, SH3BP2 deficiency suppressed the accumulation of CD3+B220+CD4−CD8−(double negative) T cells in spleen and lymph nodes, which are characteristic of Faslpr mice.

Conclusion: In the murine lupus model, SH3BP2 deficiency suppressed the development of the autoantibody (anti-dsDNA antibody), organ damage, and the accumulation of double negative T cells in the spleen. SH3BP2 could be a potential therapeutic target for autoimmune diseases.

Disclosure: K. Kawahara, Chugai Pharmaceutical Co., Ltd., 2, Glaxo Smith Kline K.K., 2; T. Mukai, Chugai Pharmaceutical Co., Ltd., 2, Glaxo Smith Kline K.K., 2; A. Nagasu, Chugai Pharmaceutical Co., Ltd., 2, Glaxo Smith Kline K.K., 2; M. Iseki, None; H. Nagasu, None; S. Tshuji, Chugai Pharmaceutical Co., Ltd., 2, Glaxo Smith Kline K.K., 2; T. Akagi, Chugai Pharmaceutical Co., Ltd., Glaxo Smith Kline K.K., 2; Y. Ueki, None; Y. Morita, Chugai Pharmaceutical Co., Ltd., 2, Glaxo Smith Kline K.K., 2.

To cite this abstract in AMA style:

Kawahara K, Mukai T, Nagasu A, Iseki M, Nagasu H, Tshuji S, Akagi T, Ueki Y, Morita Y. The Role of Adopter Protein SH3BP2 in a Murine Systemic Lupus Erythematosus Model [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/the-role-of-adopter-protein-sh3bp2-in-a-murine-systemic-lupus-erythematosus-model/. Accessed .

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