Mast cells in early rheumatoid arthritis associate with disease severity and support B cell autoantibody production

Rivellese, Felice; Mauro, Daniele; Nerviani, Alessandra; Pagani, S.; Fossati-Jimack, Liliane; Messemaker, Tobias; Kurreeman, Fina; Toes, René; Ramming, Andreas; Rauber, Simon; Schett, Georg; Jones, Gareth Wyn; Jones, Simon A.; Rossi, Francesca Wanda; Paulis, Amato de; Marone, Gianni; Shikh, Mohey Eldin El; Humby, Frances; Pitzalis, Costantino

doi:10.1136/annrheumdis-2018-213418

Cited by 53 publications

(52 citation statements)

References 56 publications

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“…Mast cells have so far not been a major focus of RA research; results from in vitro cellular experiments and in vivo animal studies have been inconsistent. Synovial mast cells have been shown to be associated with inflammation, autoantibody production, and high disease activity in early RA [25]. In this study, we investigated the role of mast cells in bone destruction during RA.…”

Section: Discussionmentioning

confidence: 99%

Joint Destructive Role of Mast Cells in Rheumatoid Arthritis

Kim²,

Won

et al. 2020

Preprint

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Background: We aimed to define the inflammatory and tissue-destructive roles of mast cells in rheumatoid arthritis (RA). Methods: Serum and synovial fluid (SF) concentration levels of tryptase, chymase, and histamine were quantified using ELISA. After activating mast cells using IL-33, the production of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMPs was determined using real-time PCR and ELISA. Osteoclastogenesis was assessed in CD14+ monocytes from peripheral blood and SF, which were cultured with IL-33-activated mast cells, by counting TRAP-positive multinucleated cells. Results: The concentration levels of serum tryptase, chymase, and histamine and SF histamine were higher in patients with RA than in controls. FceR1 and c-kit-positive mast cells were higher in RA synovium than in osteoarthritic (OA) synovium. Stimulation of mast cells by IL-33 increased the number of trypatse+chymase- and tryptase+chymase+ mast cells. IL-33 stimulation also increased the gene expression levels of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMP-9 in mast cells. Furthermore, IL-33 stimulated human CD14+ monocytes to differentiate into TRAP+ multinucleated osteoclasts. When CD14+ monocytes were co-cultured with mast cells, osteoclast differentiation was increased. Additionally, IL-33-activated mast cells stimulated osteoclast differentiation. The inhibition of intercellular contact between mast cells and monocytes using inserts reduced osteoclast differentiation. Conclusions: Mast cells and their mediators such as tryptase, chymase, and histamine were increased in RA synovial tissues and fluid. Mast cells stimulated osteoclast differentiation in monocytes. The inhibition of mast cells could be a new therapeutic option for reducing joint destruction in RA.

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Section: Discussionmentioning

confidence: 99%

Joint Destructive Role of Mast Cells in Rheumatoid Arthritis

Kim²,

Won

et al. 2020

Preprint

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“…Mast cells, strategically located in different sections of the human heart [51,52] and atherosclerotic plaque [32,33], are involved in different phases of atherosclerosis and myocardial infarction. These cells can be involved in several autoimmune disorders, such as rheumatoid arthritis [37], coeliac disease [94], multiple sclerosis [124], and bullous dermatoses [125]. Mast cell-nerve communications are involved in stress, pain, pruritus [126,127], and in inflammatory bowel diseases [35,36].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, these cells can be activated by different viral [25,26] and bacterial proteins [27,28] and thereby represent a potentially important cell during microbial infections. Therefore, the spectrum of diseases in which mast cells and their mediators have been implicated has extended to include bacterial, fungal, viral, and helminth infections [26,[29][30][31]; several diseases of the cardiovascular [14,32,33] and gastrointestinal systems [34][35][36]; and the joints [37,38]. Figure 1 schematically summarizes the wide spectrum of pathophysiological conditions in which mast cells and their mediators have been implicated during the last decades.…”

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confidence: 99%

“…Moreover, contradictory data have been obtained in animal models and from patients with long-lasting disease [101][102][103]. Rivellese and coworkers present a careful revision of the literature on mast cells in rheumatoid arthritis, including recent observations from patients with early disease indicating that these cells are relevant markers of disease severity [37,38].…”

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Mast Cells: Fascinating but Still Elusive after 140 Years from Their Discovery

Varricchi

Marone

2020

IJMS

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“…In addition to other immune cell populations, MCs have been suggested to play a crucial role, because MCs are abundant in inflamed synovial joints of RA patients, especially around blood vessels in the synovial sub-lining, at the cartilage-pannus junction at sites of cartilage erosions, and in joint fluid (Figure 1C) [comprehensively reviewed by Rivellese et al (162)]. Importantly, some of the clinical studies observed a correlation of MC numbers with joint inflammation and disease activity (163)(164)(165)(166)(167). In addition, the levels of MC mediators, including histamine and tryptase, were significantly increased in the synovial tissue of RA patients ( Figure 1C) (8,168,169).…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

The Role of Mast Cells in Bone Metabolism and Bone Disorders

et al. 2020

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Mast cells (MCs) are important sensor and effector cells of the immune system that are involved in many physiological and pathological conditions. Increasing evidence suggests that they also play an important role in bone metabolism and bone disorders. MCs are located in the bone marrow and secrete a wide spectrum of mediators, which can be rapidly released upon activation of mature MCs following their differentiation in mucosal or connective tissues. Many of these mediators can exert osteocatabolic effects by promoting osteoclast formation [e.g., histamine, tumor necrosis factor (TNF), interleukin-6 (IL-6)] and/or by inhibiting osteoblast activity (e.g., IL-1, TNF). By contrast, MCs could potentially act in an osteoprotective manner by stimulating osteoblasts (e.g., transforming growth factor-β) or reducing osteoclastogenesis (e.g., IL-12, interferon-γ). Experimental studies investigating MC functions in physiological bone turnover using MC-deficient mouse lines give contradictory results, reporting delayed or increased bone turnover or no influence depending on the mouse model used. By contrast, the involvement of MCs in various pathological conditions affecting bone is evident. MCs may contribute to the pathogenesis of primary and secondary osteoporosis as well as inflammatory disorders, including rheumatoid arthritis and osteoarthritis, because increased numbers of MCs were found in patients suffering from these diseases. The clinical observations could be largely confirmed in experimental studies using MC-deficient mouse models, which also provide mechanistic insights. MCs also regulate bone healing after fracture by influencing the inflammatory response toward the fracture, vascularization, bone formation, and callus remodeling by osteoclasts. This review summarizes the current view and understanding of the role of MCs on bone in both physiological and pathological conditions.

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Mast cells in early rheumatoid arthritis associate with disease severity and support B cell autoantibody production

Abstract: Synovial MCs identify early RA patients with a severe clinical form of synovitis characterised by the presence of ELS.

Cited by 53 publications

References 56 publications

Joint Destructive Role of Mast Cells in Rheumatoid Arthritis

Joint Destructive Role of Mast Cells in Rheumatoid Arthritis

Mast Cells: Fascinating but Still Elusive after 140 Years from Their Discovery

The Role of Mast Cells in Bone Metabolism and Bone Disorders

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