The Association Between Activation of Inflammasome and HLA-B27 in Dendritic Cells of Patients with Axial Spondyloarthritis

Jina Yeo¹, Min-Gang Kim², Hye Eun Lee³, Yeonsoo Yang², Mi Ryoung Seo¹, Hyo-Jin Choi¹, Eun Young Lee⁴, Dae Ho Lee³ and Han Joo Baek⁵, ¹Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea, ²Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea, ³Division of Endocrinology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea, ⁴3Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, ⁵Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Inchon, South Africa

Meeting: ACR Convergence 2024

Keywords: Autoinflammatory diseases, Dendritic cells, Inflammasome, innate immunity, spondyloarthritis

Session Information

Date: Saturday, November 16, 2024

Title: SpA Including PsA – Basic Science Poster

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Axial spondyloarthritis (axSpA) exhibits a predominant involvement of the innate immune system, marked by abnormal functions of innate immune cell such as dendritic cells (DCs). While it has been well established that HLA-B27 and T helper 17 (Th17) cells play a central role in the pathogenesis of axSpA, the precise link between the two factors remains unclear. Some evidence has been presented that an enhanced Th17 cells is linked to interleukin (IL)-1β secreted by activation of the inflammasome in axSpA. This study aims to evaluate that 1) the association between HLA-B27 and activation of inflammasome in DCs and 2) the role of inflammasome in mediating IL-23/IL-17 axis in patients with axSpA.

Methods: We collected blood samples from patients with axSpA. The levels of IL-1β and IL-18 in serum of axSpA patients were measured by ELISA assay, and the protein expression of cleaved caspase-1 and IL-1β in monocyte-derived DCs (moDCs) from peripheral blood mononuclear cells of axSpA was assessed by western blot assay. Flow cytometry analysis was performed to evaluate the fraction of IL-1β, IL-6 and IL-23/p19 producing DC (CD11c⁺HLA-DR⁺) of peripheral bloods obtained from the patients with axSpA. The comparison was made between HLA-B27 positive and HLA-B27 negative axSpA.

Results: Serum levels of IL-1β (p < 0.05) and IL-18 (p = ns) were higher in HLA-B27 positive-axSpA than in HLA-B27 negative axSpA. Similarly, protein expression of cleaved caspase-1 and IL-1β in moDCs cultured supernatants were higher in HLA-B27 positive axSpA compared to HLA-B27 negative axSpA. Treatment of moDC with 10 μM of nigericin induced strong expression of cleaved caspase-1 and IL-1β in cell supernatants in HLA-B27 positive axSpA (Figure 1). The percentages of IL-1β, IL-6 and IL-23/p19 producing DCs were similar between HLA-B27 positive and negative axSpA. After moDCs were stimulated with 10 μM nigericin, the rate of increase in IL-1β and IL-23/p19 was significantly higher in HLA-B27 positive axSpA compared to HLA-B27 negative axSpA (p < 0.05).

Conclusion: The activation of the inflammasome may play a pathogenic role in axSpA, with HLA-B27 potentially involved in this mechanism, though further elucidation is needed.

Figure 1. Comparison of the expression of inflammasome activation markers in monocyte-derived dendritic cells according to the presence of HLA-B27 in axial spondyloarthritis patients

Disclosures: J. Yeo: None; M. Kim: None; H. Lee: None; Y. Yang: None; M. Seo: None; H. Choi: None; E. Lee: None; D. Lee: None; H. Baek: None.

To cite this abstract in AMA style:

Yeo J, Kim M, Lee H, Yang Y, Seo M, Choi H, Lee E, Lee D, Baek H. The Association Between Activation of Inflammasome and HLA-B27 in Dendritic Cells of Patients with Axial Spondyloarthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/the-association-between-activation-of-inflammasome-and-hla-b27-in-dendritic-cells-of-patients-with-axial-spondyloarthritis/. Accessed .

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