Idiopathic Myelofibrosis: a Possible Role for Immune‐Complexes in the Pathogenesis of Bone Marrow Fibrosis

Cappio, F. Caligaris; Vigliani, R; Novarino, Anna; Camussi, Giovanni; Campana, Dario; Gavosto, F

doi:10.1111/j.1365-2141.1981.tb07192.x

Cited by 72 publications

(18 citation statements)

References 9 publications

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“…Immunological abnormalities may be also involved in the pathogenesis of idiopathic myelofibrosis. Patients with primary myelofibrosis have an increased incidence of circulating immune complexes, LE cells, antinuclear antibodies and lupus anticoagulant [21][22][23]. Gordon and Day [24], studied 19 patients with myelofibrosis and myeloid metaplasia, and found nine with circulating immune complexes and four with hypocomplementaemia, suggesting that abnormalities of the complement system may be an important part of the disease process.…”

Section: ]mentioning

confidence: 99%

Bone marrow findings in systemic lupus erythematosus patients with peripheral cytopenias

et al. 1998

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We studied 21 bone marrow specimens from 21 patients with systemic lupus erythematosus (SLE) and peripheral cytopenias: anaemia (Hb < 10 g/dl), and/or leucopenia (white blood cell count < 4 x 10(9)/l), and/or thrombocytopenia (platelets < 150 x 10(9)/l). None of the patients had used immunosuppressive drugs in the 2 months before the study, and 11 (52.4%) had never used these drugs. The global and specific series cellularity, degree of fibrosis and necrosis were evaluated by bone marrow trephine; morphological abnormalities and iron stores were evaluated by cytological smears. The most important abnormalities viewed in bone marrow biopsies were: global hypocellularity (47.6%), increased reticulin proliferation (76.2%) with myelofibrosis in one patient, and necrosis (19.0%). The marrow aspirates were difficult to obtain in four patients, who showed an increased reticulin proliferation on histological analysis. Plasmocytosis was present in 26.7% of cases and in one there was a serum monoclonal component (IgG kappa). Iron stores were normal or increased in 26.7% of specimens and decreased or absent in 73.3%. The most frequent peripheral abnormality was leucopenia in 90.4% (19/21) and granulocytic hypoplasia was observed in 47.3% (9/19) of these patients. We conclude that the bone marrow may be a target organ in SLE with cytopenias.

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Section: ]mentioning

confidence: 99%

Bone marrow findings in systemic lupus erythematosus patients with peripheral cytopenias

et al. 1998

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“…Immune-mediated mechanisms of BM fibrosis have been suggested (4,10,11) with up-regulation in the expression of extracellular matrix (ECM) proteins and cytokines such as TGF-␤, basic fibroblast growth factor, platelet-derived growth factor, and thrombopoietin (1, 14 -18). Adhesion molecules are also implicated in the development of BM fibrosis (12), and interactions with ubiquitous ECM proteins in patients with BM fibrosis could probably explain their role in this disease (12, 18 -23).…”

Section: Nf-b As a Central Mediator In The Induction Of Tgf-␤ In Monomentioning

confidence: 99%

NF-κB as a Central Mediator in the Induction of TGF-β in Monocytes from Patients with Idiopathic Myelofibrosis: An Inflammatory Response Beyond the Realm of Homeostasis

Rameshwar

Narayanan

Qian

et al. 2000

The Journal of Immunology

110

100

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Immune-mediated mechanisms have been implicated in the etiology of idiopathic bone marrow fibrosis (IMF). However, the mechanism remains poorly defined. Compared with healthy controls, IMF monocytes are overactivated, with increased production of TGF-β and IL-1. TGF-β is central to the progression of fibrosis in different organs. In the lung, fibrosis is associated with up-regulation of TGF-β-inducible genes. Because IL-1 and TGF-β have pro- and antiinflammatory properties and neither appears to regulate the high levels of each other in IMF, we studied the mechanism of this paradigm. We focused on the role of RelA, a subunit of the transcription factor, NF-κB that is associated with inflammatory responses. We transiently knocked out RelA from IMF monocytes with antisense oligonucleotides and showed that RelA is central to IL-1 and TGF-β production and to the adhesion of IMF monocytes. Because the NF-κB family comprises subunits other than RelA, we used aspirin and sodium salicylate to inhibit kinases that activate NF-κB and showed effects similar to those of the RelA knockout system. It is unlikely that RelA could be interacting directly with the TGF-β gene. Therefore, we determined its role in TGF-β production and showed that exogenous IL-1 could induce TGF-β and adherence of IMF monocytes despite the depletion of NF-κB. The results indicate that IL-1 is necessary for TGF-β production in IMF monocytes, but NF-κB activation is required for the production of endogenous IL-1. Initial adhesion activates NF-κB, which led to IL-1 production. Through autocrine means, IL-1 induces TGF-β production. In total, these reactions maintain overactivation of IMF monocytes.

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“…Platelet-derived growth factor (PDGF), transforming growth factor-|l (TGF-(l) and epidermal growth factor (EGF) are the candidates [12,[16][17][18][19], On the other hand, immunologic factors in the pathogenesis of myelofibrosis have also been suggested because patients with myelofibrosis and myeloid metaplasia have an in creased incidence of autoantibodies and circulating im mune complexes [13,[20][21][22][23][24], An overresponse of fibro blasts to autoimmune bone marrow damage or excess re lease of growth factors from platelets by binding of immune complexes to Fc receptors of platelets is spec ulated. The favorable outcome of immunosuppressive therapy in some patients with biochemical evidence of au toimmune activity supports the involvement of autoim mune bone marrow damage in the development of myelo fibrosis in a subgroup of patients [25,26].…”

Section: Discussionmentioning

confidence: 99%

Myelofibrosis and Systemic Lupus erythematosus: Reversal of Fibrosis with High-Dose Corticosteroid Therapy

et al. 1992

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A case of myelofibrosis in association with systemic lupus erythematosus (SLE) is reported. Acute thrombocytopenia and a bleeding tendency developed in a 24-year-old woman with SLE. Bone marrow aspiration was unsuccessful due to myelofibrosis. Pulse therapy with methylprednisolone reversed both thrombocytopenia and myelofibrosis. A review of the literature revealed that the coexistence of SLE and myelofibrosis is a rare occurrence. Only 7 cases, to our knowledge, have ever been reported in detail. The present case is the 3rd in which myelofibrosis was reversed by corticosteroids.

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Idiopathic Myelofibrosis: a Possible Role for Immune‐Complexes in the Pathogenesis of Bone Marrow Fibrosis

Cited by 72 publications

References 9 publications

Bone marrow findings in systemic lupus erythematosus patients with peripheral cytopenias

Bone marrow findings in systemic lupus erythematosus patients with peripheral cytopenias

NF-κB as a Central Mediator in the Induction of TGF-β in Monocytes from Patients with Idiopathic Myelofibrosis: An Inflammatory Response Beyond the Realm of Homeostasis

Myelofibrosis and Systemic Lupus erythematosus: Reversal of Fibrosis with High-Dose Corticosteroid Therapy

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