Erdheim‐Chester Disease

Khokhar, K. S; Fascia, Daniel; Scullion, David; Gough, Andrew

doi:10.1002/art.39426

Cited by 2 publications

(2 citation statements)

References 1 publication

(1 reference statement)

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“…However, the induction of other proteins that are usually regulated by S100A8/A9, such as MIP-1a, was affected to a lesser extent by blocking canonical Wnt signaling. These proteins are all well-known targets of S100A8/A9 signaling, and their association with OA has been elegantly described previously (2,3,36,37). Taken together, these data indicate that S100A8 exerts its effects partly via activation of canonical Wnt signaling, but that in addition S100A8 has b-catenin-independent effects.…”

supporting

confidence: 70%

Induction of Canonical Wnt Signaling by the Alarmins S100A8/A9 in Murine Knee Joints: Implications for Osteoarthritis

Bosch

Blom

Schelbergen

et al. 2015

Arthritis & Rheumatology

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Objective Both alarmins S100A8/A9 and canonical Wnt signaling have been found to play active roles in the development of experimental osteoarthritis (OA). However, what activates canonical Wnt signaling remains unknown. This study was undertaken to investigate whether S100A8 induces canonical Wnt signaling and whether S100 proteins exert their effects via activation of Wnt signaling. Methods Expression of the genes for S100A8/A9 and Wnt signaling pathway members was measured in an experimental OA model. Selected Wnt signaling pathway members were overexpressed, and levels of S100A8/A9 were measured. Activation of canonical Wnt signaling was determined after injection of S100A8 into naive joints and induction of collagenase‐induced OA in S100A9‐deficient mice. Expression of Wnt signaling pathway members was tested in macrophages and fibroblasts after S100A8 stimulation. Canonical Wnt signaling was inhibited in vivo to determine if the effects of S100A8 injections were dependent on Wnt signaling. Results The alarmins S100A8/A9 and members of the Wnt signaling pathway showed coinciding expression in synovial tissue in an experimental OA model. Synovial overexpression of selected Wnt signaling pathway members did not result in increased expression of S100 proteins. In contrast, intraarticular injection of S100A8 increased canonical Wnt signaling, whereas canonical Wnt signaling was decreased after induction of experimental OA in S100A9‐deficient mice. S100A8 stimulation of macrophages, but not fibroblasts, resulted in increased expression of canonical Wnt signaling members. Overexpression of Dkk‐1 to inhibit canonical Wnt signaling decreased the induction of matrix metalloproteinase 3, interleukin‐6, and macrophage inflammatory protein 1α after injection of S100A8. Conclusion Our findings indicate that the alarmin S100A8 induces canonical Wnt signaling in macrophages and murine knee joints. The effects of S100A8 are partially dependent on activation of canonical Wnt signaling.

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supporting

confidence: 70%

Induction of Canonical Wnt Signaling by the Alarmins S100A8/A9 in Murine Knee Joints: Implications for Osteoarthritis

Bosch

Blom

Schelbergen

et al. 2015

Arthritis & Rheumatology

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“…Uniquely, however, our patient presented with arthritis of several joints without intraosseous sclerosis. There have been reports of arthropathy in patients with ECD, 12 as well as arthritis and arthropathy in patients with RDD. 13–15 Monarthritis has been described before, with synovial infiltration of the affected joint by histiocytes.…”

Section: Discussionmentioning

confidence: 99%

Erdheim-Chester disease with Rosai-Dorfman-like lesions: treatment with methotrexate, anakinra and upadacitinib

et al. 2023

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Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis characterised by clonal expansion of histiocytes in various organs. These induce an inflammatory environment, which leads to damage of the affected areas. Recently, a new disease entity was proposed encompassing key features of ECD but also of Rosai-Dorfman-Destombes disease, another histiocytosis. Mitogen-activated protein kinase kinase 1 (MAP2K1)mutations seem to present a specific genetic lesion for this subtype.Here, we describe a case of this new disease entity with clinical, radiological and genetic findings compatible with ECD but histological findings compatible with Rosai-Dorfman-Destombes disease. In particular, there were intraabdominal and retroperitoneal lesions, which tested positive for a (c.167A>C; p.Q56P) mutation of the MAP2K1 gene. On histological examination, S100-positive, giant histiocytes with focal emperipolesis of haematological cells in addition to infiltration by lymphocytes and granulocytes were seen.As described for this rare variant of ECD, there was also bilateral testicular infiltration. We also describe a manifestation of oligoarthritis in this patient with ECD.The patient was treated with methotrexate and prednisolone. While radiological response to this regime was excellent, arthritis persisted. We added anakinra, which induced a response of the arthritis for more than a year. Due to treatment failure therapy was switched to upadacitinib, which induced a remission of the arthritis as well.This case adds a rare phenotype to an already rare presentation of ECD. The patient responded to immunosuppressive therapy.

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Erdheim‐Chester Disease

Cited by 2 publications

References 1 publication

Induction of Canonical Wnt Signaling by the Alarmins S100A8/A9 in Murine Knee Joints: Implications for Osteoarthritis

Induction of Canonical Wnt Signaling by the Alarmins S100A8/A9 in Murine Knee Joints: Implications for Osteoarthritis

Erdheim-Chester disease with Rosai-Dorfman-like lesions: treatment with methotrexate, anakinra and upadacitinib

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