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A Role of IgM Antibodies in Monosodium Urate Crystal Formation and Associated Adjuvanticity¹

Uliana Kanevets^*, Karan Sharma^*, Karen Dresser and Yan Shi^2,*

^* Immunology Research Group and Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada; and Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655

Uric acid is released from injured cells and can act as an adjuvant signal to the immune system. Uric acid crystals invoke strong inflammatory responses in tissues. Although their biological effects are evident and the associated signaling mechanisms are becoming clear, it remains unexplained as to why uric acid precipitates rapidly in vivo, in sharp contrast to the minimal crystallization in vitro. We report in this study that a group of IgM Abs is able to bind to these crystals, which is interesting in light that B cell-deficient mice do not sense the proinflammatory adjuvant effect of uric acid. The titers of these Abs increase upon immunization with uric acid crystals. We have produced large quantities of such mAbs. The purified IgM Abs can significantly facilitate uric acid precipitation to form the inflammatory crystals in vitro. Infusion of these Abs into B cell-deficient mice significantly increases the basal level of inflammation in these recipients and restores the host’s ability to sense uric acid’s adjuvanticity. Therefore, we have identified a factor in determining uric acid precipitation and possibly its ability to function as an endogenous adjuvant. This finding suggests a new mechanism of the pathogenesis of gouty arthritis and uric acid-induced immune activation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants to Y.S. from Alberta Heritage Foundation for Medical Research and Canadian Institutes of Health Research.

² Address correspondence and reprint requests to Dr. Yan Shi, 4A18 HRIC, 3330 Hospital Drive NW, University of Calgary, Calgary, Alberta, Canada T2N 4N1. E-mail address: yshi{at}ucalgary.ca

³ Abbreviations used in this paper: MSU, monosodium urate; DC, dendritic cell; MPO, myeloperoxidase; UBA, uric acid-binding Ab.