| Tumour necrosis factor-alpha release in peripheral blood mononuclear cells of cutaneous lupus and dermatomyositis patients. | |
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MedLine Citation:
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PMID: 22217359 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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ABSTRACT: INTRODUCTION: Several studies have reported that tumour necrosis factor-alpha (TNFalpha) is substantially increased within skin lesions of patients with discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and dermatomyositis (DM) compared to healthy controls. Elevated TNFalpha has been reported in the sera of some patients with systemic lupus erythematosus, DLE, SCLE, but not DM. Because of the key pathogenic role of autoimmunity in these diseases, we now sought to evaluate TNFalpha production by a readily available source of immune cells - namely, peripheral blood mononuclear cells (PBMCs), taken from healthy controls and from patients with cutaneous lupus or DM. METHODS: Freshly isolated PBMCs were cultured overnight and TNFalpha protein accumulation in conditioned medium was determined. In addition, flow cytometry using cell type-specific markers was performed to determine the sources of TNFalpha. Statistical comparisons used one-way analysis of variance (ANOVA) followed by the Dunnett's multiple comparison test. RESULTS: Accumulation of TNFalpha protein in conditioned medium of PBMCs from DLE patients, but not SCLE, TLE, or DM, was significantly greater (19-fold) than controls (P < 0.001). In DLE PBMCs, increased TNFalpha was produced by circulating monocytes and myeloid dendritic cells (mDCs). The mean TNFalpha fluorescence intensity, but not total number, of both monocytes and mDCs (P < 0.01) from DLE patients was significantly greater (2.3-fold) compared to healthy controls. There were significantly greater (13.3- fold) numbers of mDCs with intracellular TNFalpha in blood from DLE (P < 0.001) and DM (P < 0.001) patients compared to controls. Most importantly, a positive correlation was seen in DLE patients between their disease activity by cutaneous lupus erythematosus disease area and severity index (CLASI) and TNFalpha protein secretion (r = 0.61, P<0.08). CONCLUSIONS: TNFalpha protein production by PBMCs is greater in DLE patients than in other cutaneous forms of lupus, DM, or healthy controls. Flow cytometry studies demonstrate that circulating monocytes and mDCs contributed to this increased TNFalpha production. Monocytes and mDCs are present in lesional skin, and the increased TNFalpha production by these cells and other PBMCs likely increase the numbers of inflammatory cells seen in DLE skin relative to other subsets of CLE and dermatomyositis. These results provide a possible biological explanation for the denser infiltrate seen in DLE relative to dermatomyositis. |
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Authors:
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Adam S Nabatian; Muhammad M Bashir; Maria Wysocka; Meena Sharma; Victoria P Werth |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-4 |
Journal Detail:
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Title: Arthritis research & therapy Volume: 14 ISSN: 1478-6362 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101154438 Medline TA: Arthritis Res Ther Country: - |
Other Details:
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Languages: ENG Pagination: R1 Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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