Fumaric Acid Esters Suppress Peripheral CD4- and CD8-Positive Lymphocytes in Psoriasis

Höxtermann, Stefan; Nüchel, C.; Altmeyer, Peter

doi:10.1159/000017903

Cited by 103 publications

(93 citation statements)

References 10 publications

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“…With a rate of 3.8%, our results regarding the occurrence of leukopenia are not as pronounced as the data published in the literature [6,[11][12][13] .…”

Section: Discussioncontrasting

confidence: 74%

Lymphopenia and CD4+/CD8+ Cell Reduction under Fumaric Acid Esters

Sondermann

Rompoti²,

Leister³

et al. 2017

Dermatology

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Background: Fumaric acid esters (FAEs) are a broadly used therapy option for patients suffering from moderate-to-severe plaque psoriasis. Various studies in psoriasis have already shown peripheral blood lymphopenia during oral FAE therapy. Smaller studies also documented a reduction of CD4+ and CD8+ cell counts. Up to now, there are few case reports on opportunistic infections under FAE therapy - all of them associated with lymphopenia. Objective: To examine the influence of FAEs on white blood cells with special regard to leukocytes, lymphocytes, and CD4+ and CD8+ cells during psoriasis therapy. Patients and Methods: A cohort of 105 patients with diagnosed moderate-to-severe chronic plaque psoriasis was enrolled in this single-centre observational trial. For a cohort of 36 patients, T-cell subset analyses were performed. Results: Of the total, 65 patients were male (61.9%) and 40 (38.1%) female; the mean age was 43.3 years (range 16-73 years). The median lymphocyte count was significantly reduced by about 35.8% after the first 6 months of therapy. When assessing the lymphocyte count nadir over the whole period observed, 46.7% of the patients developed lymphopenia. Severe lymphopenia (<500/µL) was documented in 11.4% of the patients. The CD4+ and CD8+ cell counts were significantly reduced by about 30.2 and 45.3%, respectively. Conclusion: To the best of our knowledge this is the largest clinical investigation analysing prospectively CD4+ and CD8+ cell counts in psoriasis patients receiving FAEs. We suggest periodic monitoring of absolute lymphocyte counts as well as the establishment of the determination of T-cell subsets prior to and during therapy.

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“…With a rate of 3.8%, our results regarding the occurrence of leukopenia are not as pronounced as the data published in the literature [6,[11][12][13] .…”

Section: Discussioncontrasting

confidence: 74%

Lymphopenia and CD4+/CD8+ Cell Reduction under Fumaric Acid Esters

Sondermann

Rompoti²,

Leister³

et al. 2017

Dermatology

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“…We now demonstrated that dimethylfumarate at a rather low concentration of 3 ÌM, which did not exhibit special antiproliferative activity, inhibited the IFN-Á-induced K17 overexpression. This finding adds another facet to the understanding of the obviously multimodal, partly anti-inflammatory and immunomodulating [36][37][38][39], and partly antiproliferative mechanism of the drug's action [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Dithranol and Dimethylfumarate Suppress the Interferon-γ-Induced Up-Regulation of Cytokeratin 17 as a Putative Psoriasis Autoantigen in vitro

Bonnekoh

Böckelmann²,

Ambach³

et al. 2001

Skin Pharmacol Physiol

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In psoriasis an etiopathogenetic vicious circle has been hypothesized in which disease manifestation is triggered by skin-specific autoantigen structures. Autoreactive T cells are supposed to mediate inflammation and hyperproliferation in the epidermopapillary compartment, positively feeding back the expression and accessibility of decisive antigen structures. Recently an epitope within cytokeratin 17 (K17) has been described as such a putative psoriasis autoantigen, which is moreover known to be up-regulated under the influence of proinflammatory interferon-γ (IFN-γ), which is abundantly detected in psoriatic plaques. The present study proposes an in vitro model for this presumptive IFN-γ/K17 autoimmune loop, i.e. the incubation of hyperproliferative human HaCaT keratinocytes with 25 U IFN-γ/ml for 72 h. This treatment led to a significant up-regulation of K17 protein expression (≧300%) measured by flow immunocytometry as compared to the untreated control (100%, p ≤ 0.05). Preincubation with a subcytotoxic and antiproliferative dithranol concentration as low as 0.3 µM for 2 h prior to the IFN-γ exposure resulted in a K17 expression that was significantly lower than the IFN-γ-induced K17 expression reference level. The IFN-γ-induced K17 expression was also significantly lowered by coincubation with a subcytotoxic and nonantiproliferative concentration of 3 µM dimethylfumarate. The data indicate for dithranol and dimethylfumarate that a part of their antipsoriatic mode of action may be related to a direct down-regulation of putative psoriasis autoantigen structures.

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“…Flow-cytometric examinations of peripheral blood cells of psoriasis patients showedin parallel to the clinical effect of FAE treatment -decreased numbers of T and B lymphocytes but not of natural killer cells [24].…”

Section: Patient 2 Historymentioning

confidence: 91%