Session Information
Session Title: B cell Biology and Targets in Autoimmune Disease: Rheumatoid Arthritis and Related Diseases
Session Type: Abstract Submissions (ACR)
Background/Purpose Whole blood flow cytometric analysis and serum protein profiling were commonly utilized to characterize disease-specific alterations in a wide variety of autoimmune diseases. However, precise mechanisms underlying their pathophysiological conditions were still obscure because each experimental approach was carried out independently and not well integrated. Therefore, we performed comprehensive flow cytometric analysis by multi-colored staining in combination with serum protein profile to fully understand pathophysiological aspects in rheumatoid arthritis (RA) and primary Sjogren’s syndrome (pSS).
Methods Heparinized peripheral blood was collected from untreated RA patients (N = 51), pSS patients (N = 60), and healthy controls (N = 36). Fresh whole blood was immediately stained with fluorescent-labeled antibodies and analyzed with 3-laser, 8-color FACS equipment. Over a thousand of serum protein profile were also obtained with aptamer technology from SomaLogic, Inc. Serum immunoglobulin concentrations were evaluated by ELISA and gene expression levels were analyzed using quantitative real-time PCR.
Results Among over 40 immune cell subsets we investigated, surface IgD+ CD38++ B cells, called pre-germinal center B (pre-GC B), were significantly increased in both RA and pSS patients. Interestingly, serum IgG but not IgM and IgA was positively correlated with the number of pre-GC B cells in pSS but not RA, suggesting their distinct role in pSS pathogenesis. Consistent with this, GC-related serum proteins such as PD-L2, SLAMF2, and CD30 ligand were significantly elevated and correlated with pre-GC B in pSS but not RA. Furthermore, pre-GC B cells isolated from pSS patients exhibited higher GC-related gene expressions including XBP1 and BACH2 than those from healthy controls.
Conclusion Our findings suggest possible role of pre-GC B in pSS pathogenesis through IgG production and germinal center formation. By integrating multiple comprehensive analyses, we identified a novel immune cell phenotype, indicating this strategy as a useful tool to highly impact on better understanding of autoimmune diseases.
Disclosure:
Y. Kassai,
Takeda Pharmaceutical Company Limited,
3;
K. Suzuki,
None;
R. Morita,
None;
M. Takiguchi,
Takeda Pharmaceutical Company Limited,
3;
R. Kurisu,
Takeda Pharmaceutical Company Limited,
3;
T. Miyazaki,
Takeda Pharmaceutical Company Limited,
3;
A. Yoshimura,
None;
T. Takeuchi,
Abbott Japan Co., Ltd., Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Sanofi–Aventis K.K., Santen Pharmaceutica,
2,
Abbott Japan Co., Ltd., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Astellas Pharma, Daiichi Sankyo Co.,Ltd.,
8,
Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., Abbvie GK, Daiichi Sankyo Co.,Ltd.,
5.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/integrated-comprehensive-analysis-of-immune-cell-subsets-and-serum-protein-profile-identifies-the-role-of-pre-germinal-center-b-cells-in-sjogrens-syndrome-pathogenesis/