Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: Results of a pilot, multicenter, multiple-dose, placebo-controlled study

Gottlieb, Alice B.; Lebwohl, Mark; Shirin, Sophie; Sherr, Amelia; Gilleaudeau, Patricia; Singer, Giselle; Solodkina, Galina; Grossman, Rachel; d, Elvira Gisoldi; Phillips, Stephanie; Neisler, H.Mike; Krueger, James G.

doi:10.1067/mjd.2000.107945

Cited by 120 publications

(75 citation statements)

References 35 publications

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“…However, this model describes an acute and simple skin inflammation, and thus, it has disadvantages in evaluating the maintenance of human chronic disease. Regarding cell types responsible for IL-17 production, gd-T cells are main producers of IL-17 in a murine model of psoriasiform dermatitis 33,36 , whereas gd-T cells take up a minority of IL-17-producing cells and conventional ab-T cells produce most of IL-17 in the inflammation site of human psoriasis 58,59 . Thus, we also examined the effect of adiponectin on IL-17 production by human CD4-and CD8-positive T cells.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

et al. 2015

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Accumulating epidemiologic evidence has revealed that metabolic syndrome is an independent risk factor for psoriasis development and is associated with more severe psoriasis. Adiponectin, primarily recognized as a metabolic mediator of insulin sensitivity, has been newly drawing attention as a mediator of immune responses. Here we demonstrate that adiponectin regulates skin inflammation, especially IL-17-related psoriasiform dermatitis. Mice with adiponectin deficiency show severe psoriasiform skin inflammation with enhanced infiltration of IL-17-producing dermal Vg4 þ gd-T cells. Adiponectin directly acts on murine dermal gd-T cells to suppress IL-17 synthesis via AdipoR1. We furthermore demonstrate here that the adiponectin level of skin tissue as well as subcutaneous fat is decreased in psoriasis patients. IL-17 production from human CD4-or CD8-positive T cells is also suppressed by adiponectin. Our data provide a regulatory role of adiponectin in skin inflammation, which would imply a mechanism underlying the relationship between psoriasis and metabolic disorders.

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Section: Discussionmentioning

confidence: 99%

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

et al. 2015

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“…Taken together, psoriasis is regarded as a type 1 T cell (Th1)-associated disease, since alterations in cytokine production both locally and systemically have been demonstrated (Schön and Boehncke, 2005;Lowes et al, 2007). As a result, systematically administered anti-lymphocyte and anti-tumor necrosis factor alpha (TNF-α) antibodies have been proven to provide impressive improvement of psoriasis (Krueger et al, 2000;Gottlieb et al, 1995Gottlieb et al, , 2000Gottlieb et al, , 2003Kupper, 2003).…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of Id1 in peripheral blood of psoriatic patients

Ronpirin

Achariyakul²,

Tencomnao³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. Although the precise causes of psoriasis are unclear, it is widely accepted that psoriasis is a disorder in which factors in the immune system, enzymes, and other biochemical substances that regulate skin cell division are impaired, leading to rapid proliferation of keratinocytes and incomplete keratinization. Expression of the helix-loop-helix transcription factor Id1 (inhibitor of differentiation/DNA binding), functioning as an inhibitor of differentiation, is known to increase in psoriatic skin. However, the molecular involvement of this particular biomarker in the psoriatic immune system remains to be elucidated. We measured Id1 mRNA expression in peripheral blood mononuclear cells (PBMCs) of psoriatic patients and healthy controls using semi-quantitative reverse transcriptase- PCR. The normalized level of Id1 transcripts in psoriatic patients was about 2-fold higher than that in controls (P < 0.05). When we examined the proliferation rate of PBMCs, the stimulation index obtained from the phytohemagglutinin stimulation assay was not significantly different in psoriatic patients. In patients with psoriasis, there was no correlation between the stimulation index and the psoriasis area severity index. We suggest that Id1 has a role in causing psoriatic immune cell symptoms.

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“…For example, an LFA-3 Ig fusion protein (alefacept) has been found to reduce psoriatic lesions (36), and a different fusion protein, CTLA4Ig, which blocks CD28:CD80/CD86 interactions, also improved psoriatic lesions (37). Attempts to modulate T cells directly in psoriasis include the use of antibodies directed against CD3 (38) and CD4 (39), and a fusion protein containing the cell-binding domain of diphtheria toxin (i.e., denileukin diftitox) has been produced to target and kill activated T cells bearing receptors for IL-2 (40).…”

Section: The Immunological Synapse and Psoriasismentioning

confidence: 99%

Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities

Nickoloff¹,

Nestle²

2004

J. Clin. Invest.

278

221

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psoriasis patients. As a prevalent T lymphocyte-mediated disorder, psoriasis, as well as the side effects associated with its treatment, affects patients globally. In this review, recent progress is discussed in the areas of genetics, the immunological synapse, the untangling of the cytokine web and signaling pathways, xenotransplantation models, and the growing use of selectively targeted therapies. Since psoriasis is currently incurable, new management strategies are proposed to replace previous serendipitous approaches. Such strategic transition from serendipity to the use of novel selective agents aimed at defined targets in psoriatic lesions is moving rapidly from research benches to the bedsides of patients with this chronic and debilitating disease.

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Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: Results of a pilot, multicenter, multiple-dose, placebo-controlled study

Cited by 120 publications

References 35 publications

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

Up-regulation of Id1 in peripheral blood of psoriatic patients

Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities

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