The expression of BAFF in the muscles of patients with dermatomyositis

Baek, Ahmi; Park, Hyung Jun; Na, Sang-Jun; Shim, Dong Suk; Moon, Jean; Yang, Young; Choi, Young Chul

doi:10.1016/j.jneuroim.2012.04.006

Cited by 42 publications

(29 citation statements)

References 33 publications

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“…Therefore, it can be speculated that IFN-g2modulated BAFF expression in mucosal epithelial cells is responsible for diverse mucosa-associated diseases linked to intestinal inflammation and autoimmunity. Available evidence indicates that locally concentrated BAFF plays critical roles in a number of autoinflamed tissue types in which lymphoid neogenesis occurs (62)(63)(64)(65). Furthermore, increases in BAFF levels are positively correlated with the intensities of local inflammatory responses (10,66).…”

Section: Discussionmentioning

confidence: 99%

SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress

Hun

Choi

Kim

et al. 2013

The Journal of Immunology

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Although the activation of B cells in the gastrointestinal tract is of great importance in the context of immunity to pathogens and mucosal inflammatory diseases, little is known about the mechanisms responsible for the local activation of B cells in the subepithelial area of the intestine. Epithelium-derived BAFF is the major modulator of B cell development and Ig class switching. The present study was performed to address the molecular mechanism of BAFF expression in gut epithelial cells in the presence of proinflammatory stimuli. Inflammation-induced BAFF expression in mucosal epithelial cells might be responsible for diverse mucosa-associated diseases linked to intestinal inflammation and autoimmunity. Although BAFF was marginally expressed in unstimulated epithelial cells, BAFF mRNA was significantly upregulated by proinflammatory IFN-γ. Furthermore, IFN-γ triggered JAK/STAT1 signals via the cytokine receptor, which contributed to epithelial BAFF upregulation. In terms of signaling intervention, ribosomal insult attenuated IFN-γ–activated JAK/STAT signal transduction and subsequent BAFF induction in gut epithelial cells. Ribosomal insults led to the superinduction of SOCS3 by enhancing its mRNA stability via HuR RNA-binding protein. Upregulated SOCS3 then contributed to the blocking of the JAK/STAT-linked signal, which mediated BAFF suppression by ribosomal stress. All of these findings show that ribosomal stress–induced SOCS3 plays a novel regulatory role in epithelial BAFF production, suggesting that epithelial ribosomal dysfunction in association with SOCS3 may be a promising therapeutic point in BAFF-associated human mucosal diseases.

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Section: Discussionmentioning

confidence: 99%

SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress

Hun

Choi

Kim

et al. 2013

The Journal of Immunology

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“…Pairwise comparisons demonstrated that 23 proteins had significantly higher concentrations in IFN-hi ( P < 0.05) but not IFN-lo patients compared with HCs, suggesting a unique proteomic feature of IFN-hi myositis patients. Twenty cytokines were up-regulated in our DM or PM patient cohort, many of which have been reported to be overexpressed in muscle tissue sections of IIMs, such as IL-18, monocyte chemoattractant protein 1 (MCP-1), and B-cell activating factor (BAFF) [15, 16]. Several soluble cytokine receptors and adhesion molecules [IL-2RA, TNF receptor 1 (TNFR1), TNFR2, and vascular cell adhesion molecule 1 (VCAM-1)] demonstrated elevated levels in DM or PM patients, which was consistent with previous reports [17–19].…”

Section: Resultsmentioning

confidence: 99%

“…IL-18 is a Th1 cytokine that induces proliferation and differentiation of naive T cells. Previous reports have demonstrated overexpression of three T cell-associated proteins in the serum of IIM patients [15–18, 30–32]. BAFF, MCP-1 and MCP-2 are also involved in T cell regulation and chemotaxis, among other functions.…”

Section: Discussionmentioning

confidence: 99%

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Suppression of soluble T cell-associated proteins by an anti-interferon- monoclonal antibody in adult patients with dermatomyositis or polymyositis

et al. 2013

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Objective. The aim of this study was to identify serum markers that are modulated by an investigational anti-IFN-α mAb, sifalimumab, in adult DM or PM patients.Methods. In a phase 1b clinical trial, sera were collected from a total of 48 DM or PM adult patients receiving either placebo for 3 months or sifalimumab for 6 months. Samples were tested for 128 selected proteins using a multiplex luminex immunoassay. Muscle biopsies from selected patients were stained for T cell infiltration using an anti-CD3 antibody.Results. A robust overexpression of multiple serum proteins in DM or PM patients was observed, particularly in patients with an elevated baseline type I IFN gene signature in the blood or muscle. Neutralization of the type I IFN gene signature by sifalimumab resulted in coordinated suppression of T cell-related proteins such as soluble IL-2RA, TNF receptor 2 (TNFR2) and IL-18. Muscle biopsies from two patients with the highest serum protein suppression were selected and found to have a pronounced reduction of muscle T cell infiltration. Down-regulation of IL-2RA correlated with favourable manual muscle test 8 (MMT-8) alterations in sifalimumab-dosed patients.Conclusion. A reduced level of multiple T cell-associated proteins after sifalimumab but not placebo administration suggests a suppressive effect of blocking type I IFN signalling on T cell activation and chemoattraction that may lead to a reduction of T cell infiltration in the muscle of myositis patients. Further, soluble IL-2RA changes from baseline may serve as a responsive and/or predictive marker for type I IFN-targeted therapy in adult DM or PM patients.

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“…BAFF can be induced by type 1 IFN stimulation of myeloid DCs [55] and has been shown induced in epithelial cells treated with IFN-c [56]. Increased levels of BAFF mRNA were detected in DM muscle compared to normal controls, and expression of BAFF protein localised to the perifascicular muscle fibres [57].…”

Section: Cytokinesmentioning

confidence: 96%

Interferons as components of the complex web of reactions sustaining inflammation in idiopathic inflammatory myopathies

Paepe

2015

Cytokine

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The expression of BAFF in the muscles of patients with dermatomyositis

Cited by 42 publications

References 33 publications

SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress

SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress

Suppression of soluble T cell-associated proteins by an anti-interferon- monoclonal antibody in adult patients with dermatomyositis or polymyositis

Interferons as components of the complex web of reactions sustaining inflammation in idiopathic inflammatory myopathies

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