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

Kanevets, Uliana; Sharma, Karan; Dresser, Karen; Shi, Yan

doi:10.4049/jimmunol.0803777

Cited by 61 publications

(53 citation statements)

References 44 publications

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“…One can imagine that sufficient uric acid to induce endogenous inflammatory responses only occurs with large-scale cell death and must be associated with uric acid precipitation; in other words, a general antioxidant is converted into a strong inflammatory stimulant only upon its phase transition (6). Although the work of Kono et al did not address this specific issue (5), recent data have suggested that serum antibodies against uric acid may facilitate its crystallization (17).…”

Section: Not So Trivial Triviamentioning

confidence: 69%

Caught red-handed: uric acid is an agent of inflammation

Shi¹

2010

J. Clin. Invest.

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Section: Not So Trivial Triviamentioning

confidence: 69%

Caught red-handed: uric acid is an agent of inflammation

Shi¹

2010

J. Clin. Invest.

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“…Terkeltaub showed that the inflammatory response to MSU crystals could be inhibited by apo B lipoprotein (50). Kanevets et al have recently demonstrated substantial amounts of uric acid-binding antibodies in unimmunized mice (51), and Ig-coated MSU crystals have been observed in gout specimens (summarized in Kanevets,ref. 51).…”

Section: Discussionmentioning

confidence: 99%

“…51). Uric acid-binding antibodies facilitated urate crystal formation but did not block uric acid-mediated activation of dendritic cells (51). Further work is indicated to evaluate for the presence of uric acid-binding antibodies in OA synovial fluids as another possible potentiator of crystal formation.…”

Section: Discussionmentioning

confidence: 99%

Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation

Denoble¹,

Huffman²,

Stäbler³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

232

178

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Uric acid (UA) is known to activate the NLRP3 (Nacht, leucine-rich repeat and pyrin domain containing protein 3) inflammasome. When activated, the NLRP3 (also known as NALP3) inflammasome leads to the production of IL-18 and IL-1β. In this cohort of subjects with knee osteoarthritis (OA), synovial fluid uric acid was strongly correlated with synovial fluid IL-18 and IL-1β. Synovial fluid uric acid and IL-18 were strongly and positively associated with OA severity as measured by both radiograph and bone scintigraphy, and synovial fluid IL-1β was associated with OA severity but only by radiograph. Furthermore, synovial fluid IL-18 was associated with a 3-y change in OA severity, on the basis of the radiograph. We conclude that synovial fluid uric acid is a marker of knee OA severity. The correlation of synovial fluid uric acid with the two cytokines (IL-18 and IL-1β) known to be produced by uric acidactivated inflammasomes and the association of synovial fluid IL-18 with OA progression, lend strong support to the potential involvement of the innate immune system in OA pathology and OA progression.arthritis | inflammation | interleukin-18 | interleukin-1β | tumor necrosis factor alpha U ric acid (UA) is constitutively present in normal cells, increased in concentration when cells are injured, and released from dying cells (1). On the basis of a theory proposed by Matzinger, the products of cell stress and tissue damage may represent "danger signals" that function as endogenous adjuvants recognized by the immune system (2). Matzinger proposed that immunity is controlled by an internal conversation between tissues and the cells of the immune system (3). This proposal introduced a new immunological model of an immune system capable of sensing cellular stress and tissue damage (4). Shi subsequently identified uric acid as one of these principal endogenous danger signals released from injured cells and mediating the immune response to antigens associated with injured cells (1). The molecular mechanism of this innate immune response to uric acid was further shown to be the result of the activation of the NALP3 inflammasome, a cytosolic, multiprotein complex that mediates caspase activation by uric acid crystals, leading to the production of the active forms of IL-1β and IL-18 (5). Recently, Kono et al. demonstrated in an in vivo hepatoxicity mouse model that uric acid is a physiological regulator of the inflammation induced by tissue injury (6). These data form the basis for our hypothesis that synovial fluid uric acid is a factor regulating tissue inflammation, disease severity, and progression in osteoarthritis (OA).Uric acid is best known for its role in gout. When uric acid concentrations exceed the limit of solubility (∼6.8 mg/dL or even lower under conditions of low pH or temperature), crystal formation can ensue, which is capable of activating the NALP3 inflammasome (5) and triggering the acute severe attacks of joint inflammation characteristic of gout (7). Several studies have previously posited an association o...

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“…On one hand, natural IgM reduces the inflammatory response by removing the apoptotic cells and preventing inflammatory arthritis (121) and atherosclerosis (91). On the other hand, natural IgM enhances inflammation through increasing the precipitation of urate crystals, which recruits neutrophils and worsens inflammation (122). Natural IgM is also involved in ischemia-reperfusion injury, including myocardial infarction and intestinal ischemia-reperfusion injury, wherein it targets autoantigen-expressing endothelial cells (123,124).…”

Section: Implications Of Natural Abs In Autoimmunity and Inflammatorymentioning

confidence: 99%

Natural Antibodies Bridge Innate and Adaptive Immunity

Panda

Ding

2015

The Journal of Immunology

268

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Natural Abs, belonging to isotypes IgM, IgG3, and IgA, were discovered nearly half a century ago. Despite knowledge about the role of the polyreactive natural IgM in pathogen elimination, B cell survival and homeostasis, inflammatory diseases, and autoimmunity, there is a lack of clarity about the physiological role of natural IgG and natural IgA because they appear incapable of recognizing Ags on their own and are perceived as nonreactive. However, recent research revealed exciting functions of natural IgG in innate immunity. Natural IgG:lectin collaboration swiftly and effectively kills invading pathogens. These advances prompt further examination of natural Abs in immune defense and homeostasis, with the potential for developing novel therapeutics. This review provides new insights into the interaction between natural Abs and lectins, with implications on how interactions between molecules of the innate and adaptive immune systems bridge these two arms of immunity.

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

Cited by 61 publications

References 44 publications

Caught red-handed: uric acid is an agent of inflammation

Caught red-handed: uric acid is an agent of inflammation

Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation

Natural Antibodies Bridge Innate and Adaptive Immunity

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