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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1386939
This article is part of the Research Topic Community Series in Advances in Pathogenesis and Therapies of Gout: Volume II View all 4 articles

The Impact of AIM2 Inflammasome-Induced Pyroptosis on Acute Gouty Arthritis and Asymptomatic Hyperuricemia Patients

Provisionally accepted
Jiyan Chu Jiyan Chu 1Jing Tian Jing Tian 2Ping Li Ping Li 3*Diyu Fu Diyu Fu 3Lin Guo Lin Guo 3Rui Sun Rui Sun 3
  • 1 Department of Radiology, Northern Theater General Hospital, Shenyang, Liaoning Province, China
  • 2 Department of Orthopaedics, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China
  • 3 Department of Rheumatology, General Hospital of Northern Theater Command, Shenyang, China

The final, formatted version of the article will be published soon.

    Objective: This study aimed to evaluate the role of absent in melanoma 2 (AIM2) inflammasome-mediated pyroptosis in the pathogenesis of acute gouty arthritis (AGA) and asymptomatic hyperuricemia(AHU). Methods: A cohort of 30 AGA patients, 30 AHU individuals, and 30 healthy controls (HC) was assembled. Demographic and biochemical data, along with blood samples, were collected. Serum double-stranded DNA (dsDNA) levels were quantified using a fluorescent assay. Transcriptomic and proteomic analysis of AIM2, Caspase-1, GSDMD, IL-1β, and IL-18 in peripheral blood mononuclear cells was performed using qRT-PCR and Western blot. Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum IL-1β and IL-18. Spearman correlation analysis was utilized to assess relationships between variables. Results: Both AGA and AHU groups demonstrated elevated metabolic indicators and serum levels of dsDNA, IL-1β, and IL-18 compared to the HC group.AGA patients exhibited higher inflammatory markers than the AHU group. In the AGA group, there was a significant increase in the mRNA and protein levels of AIM2, Caspase-1, GSDMD, IL-1β, and IL-18 (P<0.05 to P<0.001). The AHU group showed higher AIM2, Caspase-1, GSDMD, and IL-18 mRNA levels than the HC group (P<0.001 to P<0.01), with a nonsignificant increase in AIM2, GSDMD, and IL-1β proteins (P>0.05). In contrast, Caspase-1 and IL-18 proteins were significantly higher in the AHU group (P<0.05). Notable correlations were observed between AIM2 protein expression and levels of Caspase-1 and GSDMD in both AGA and AHU groups. In the AGA group, AIM2 protein correlated with IL-1β, but not in the AHU group. The AIM2 protein in the AHU group was positively associated with IL-18, with no such correlation in the AGA group. Conclusion: AIM2 inflammasome may play a role in the inflammatory processes of AGA and AHU and that its activation may be related to the pyroptosis pathway.

    Keywords: Absent in melanoma 2(AIM2), pyroptosis, caspase-1, gasdermin D (GSDMD), Acute gouty arthritis, Asymptomatic hyperuricemia

    Received: 16 Feb 2024; Accepted: 05 Jul 2024.

    Copyright: © 2024 Chu, Tian, Li, Fu, Guo and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ping Li, Department of Rheumatology, General Hospital of Northern Theater Command, Shenyang, China

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