Epigenetics in systemic lupus erythematosus

Xiao, Gong; Zuo, Xiaoxia

doi:10.3892/br.2015.556

Cited by 20 publications

(15 citation statements)

References 66 publications

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“…SCLE is characterized by annular or psoriasiform cutaneous lesions located above the waist (neck, trunk and outer aspect of the arms) ( 14 ). The following etiologic factors are associated with SCLE: Genetic predisposition (human leukocyte antigen-DR3); immunological factors (60% of cases are positive for total antinuclear antibodies, of which 80% of cases are associated with the presence of anti-Ro antibodies; environmental factors (exposure to ultraviolet radiation, radiotherapy, psoralen combined with ultraviolet A treatment and certain drugs, including thiazide diuretics, calcium blockers, statins, inhibitors of angiotensin converting enzyme, terbinafine and griseofulvin) ( 15 , 19 – 22 ); and an epigenetics study has reported that autoreactive T cells and B cells in patients with SCLE have evidence of altered patterns of DNA methylation, modifications of histones and microRNA) ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Drug-induced Rowell syndrome, a rare and difficult to manage disease: A case report

et al. 2017

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Rowell syndrome is defined as the association between lupus erythematosus, erythema multiforme-like lesions and characteristic immunological changes including positive tests for rheumatoid factor, speckled antinuclear antibody, positive anti-Ro or anti-La antibodies. The present report presents the case of a 45-year-old female patient who was previously diagnosed in January 2010 with terbinafine-induced subacute cutaneous lupus erythematosus and was admitted for a skin eruption consisting of erythematous-papular erythema multiforme-like lesions, primarily on the trunk and limbs. The associated symptoms consisted of fatigability, myalgia and gonalgia. In October 2015, the illness reoccurred ~1 week after the initiation of Helicobacter pylori eradication treatment. Anti-Ro antibodies, rheumatoid factor and antinuclear antibody tests were positive. Given the patient's medical history, clinical manifestations, and laboratory, histopathological and immunofluorescence microscopy findings, a diagnosis of Rowell syndrome was made. Systemic corticosteroids (methylprednisolone; 0.5 mg/kg/day) and immunomodulatory therapy (azathioprine; 50 mg/day) were administered with the associated medication (omeprazole, 20 mg/day; KCl, 1 g/day) and topical dermocorticoids (fluticasone propionate 0.05% cream; 1 application/day), with a favorable outcome. The major diagnostic criteria for Rowell syndrome are the presence of lupus erythematosus (acute, subacute or systemic), erythema multiforme-like lesions and positive testing for antinuclear antibodies. The minor diagnostic criteria for Rowell syndrome are chilblains, the presence of anti-Ro antibodies and positive testing for rheumatoid factor. A diagnosis of Rowell syndrome is made if the patient exhibits all major criteria and at least one minor criterion. The present case met all diagnostic criteria, excluding the presence of chilblains. Notably, in this case there was a co-occurrence of subacute lupus erythematosus and Rowell syndrome lesions, which was drug-induced.

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Section: Discussionmentioning

confidence: 99%

Drug-induced Rowell syndrome, a rare and difficult to manage disease: A case report

et al. 2017

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“…LN occurs in approximately 50% of SLE patients and is a major cause of morbidity and mortality in this disease [9]. Recently, several studies have provided evidence that epigenetic factors play a crucial role in the initiation and progression of the development of SLE, including LN [10]. Epigenetic factors include miRNA, methylation of DNA and acetylation of histones as well as non-histone proteins.…”

Section: Introductionmentioning

confidence: 99%

Selective HDAC6 inhibition decreases early stage of lupus nephritis by down-regulating both innate and adaptive immune responses

Ren

Liao

Vieson

et al. 2017

Clinical and Experimental Immunology

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SUMMARYWe have demonstrated previously that histone deacetylase (HDAC6) expression is increased in animal models of systemic lupus erythematosus (SLE) and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Additionally, we sought to delineate the cellular and molecular mechanism(s) of action of a selective HDAC6 inhibitor in SLE. We treated 20-week-old (early-disease) New Zealand Black (NZB)/White F 1 female mice with two different doses of the selective HDAC6 inhibitor (ACY-738) for 5 weeks. As the mice aged, we determined autoantibody production and cytokine levels by enzyme-linked immunosorbent assay (ELISA) and renal function by measuring proteinuria. At the termination of the study, we performed a comprehensive analysis on B cells, T cells and innate immune cells using flow cytometry and examined renal tissue for immune-mediated pathogenesis using immunohistochemistry and immunofluorescence. Our results showed a reduced germinal centre B cell response, decreased T follicular helper cells and diminished interferon (IFN)-g production from T helper cells in splenic tissue. Additionally, we found the IFN-a-producing ability of plasmacytoid dendritic cells was decreased along with immunoglobulin isotype switching and the generation of pathogenic autoantibodies. Renal tissue showed decreased immunoglobulin deposition and reduced inflammation as judged by glomerular and interstitial inflammation. Taken together, these studies show selective HDAC6 inhibition decreased several parameters of disease pathogenesis in lupusprone mice. The decrease was due in part to inhibition of B cell development and response.

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“…Interactions between DNA methylation and other epigenetic events are briefly discussed. A detailed discussion of involved mechanisms, however, is beyond the scope of this manuscript and reviewed elsewhere [16,17].…”

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confidence: 99%

DNA Methylation in Systemic Lupus Erythematosus

et al. 2016

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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease facilitated by aberrant immune responses directed against cells and tissues, resulting in inflammation and organ damage. In the majority of patients, genetic predisposition is accompanied by additional factors conferring disease expression. While the exact molecular mechanisms remain elusive, epigenetic alterations in immune cells have been demonstrated to play a key role in disease pathogenesis through the dysregulation of gene expression. Since epigenetic marks are dynamic, allowing cells and tissues to differentiate and adjust, they can be influenced by environmental factors and also be targeted in therapeutic interventions. Here, we summarize reports on DNA methylation patterns in SLE, underlying molecular defects and their effect on immune cell function. We discuss the potential of DNA methylation as biomarker or therapeutic target in SLE.

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Epigenetics in systemic lupus erythematosus

Cited by 20 publications

References 66 publications

Drug-induced Rowell syndrome, a rare and difficult to manage disease: A case report

Drug-induced Rowell syndrome, a rare and difficult to manage disease: A case report

Selective HDAC6 inhibition decreases early stage of lupus nephritis by down-regulating both innate and adaptive immune responses

DNA Methylation in Systemic Lupus Erythematosus

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