Treatment of Chronic Plaque Psoriasis by Selective Targeting of Memory Effector T Lymphocytes

Ellis, Charles N.; Krueger, Gerald G.

doi:10.1056/nejm200107263450403

Cited by 543 publications

(445 citation statements)

References 19 publications

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“…A potential drawback of this approach might be an increased risk of infection. However, we did not observe any increase in infection rate, which is consistent with previous observations (26).…”

Section: Discussionsupporting

confidence: 93%

“…For that reason, we focused on the number of memory-effector T cells in serial samples of both the PB and the synovial compartment. In the PB, we confirmed the reduction of circulating CD4ϩ,CD45ROϩ T cells during the course of treatment, as previously observed in patients with plaque psoriasis (26). Moreover, there was a similar reduction in the synovial compartment.…”

Section: Discussionsupporting

confidence: 89%

“…The importance of T cells in the pathogenesis of PsA has encouraged the development of compounds such as alefacept, which interferes with T cell activation and induces selective T cell apoptosis (21)(22)(23)(24)(25). The data presented in this report support the notion that targeted therapies are effective in patients with PsA, as recently shown in plaque psoriasis (26).…”

Section: Discussionsupporting

confidence: 80%

“…The LFA-3 portion binds to the CD2 receptor on T lymphocytes, blocking T cell activation and proliferation in vitro and in vivo, while the IgG1 domain interacts with Fc␥ receptor type III on accessory cells (e.g., macrophages and natural killer cells) to induce selective apoptosis of memory-effector T lymphocytes (21)(22)(23)(24)(25). In a recently completed phase II clinical trial, alefacept was documented to be safe and clinically efficacious compared with placebo in patients with active plaque psoriasis (26). In this same study, it was documented that alefacept administration resulted in a significant and selective reduction in effector T cells without major safety problems.…”

mentioning

confidence: 99%

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Alefacept treatment in psoriatic arthritis: Reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis

Kraan

Kuijk

Dinant

et al. 2002

Arthritis & Rheumatism

135

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Objective. To investigate whether alefacept (a fully human lymphocyte function-associated antigen 3 [LFA-3]/IgG1 fusion protein that blocks the LFA-3/CD2 interaction) is able to reduce the signs and symptoms of joint inflammation in patients with active psoriatic arthritis (PsA).Methods. Eleven patients with active PsA were treated with alefacept for 12 weeks in an open-label and explorative study. Clinical joint assessment and laboratory assessments were performed at baseline and after 4, 9, 12, and 16 weeks of treatment. Serial synovial tissue (ST) biopsy specimens from an inflamed index joint (knee, ankle, wrist, or metacarpophalangeal joint) were obtained by arthroscopy at baseline and after 4 and 12 weeks of treatment.Results. At the completion of treatment, 6 of 11 patients (55%) fulfilled the Disease Activity Score (DAS) response criteria. Nine patients (82%) fulfilled the DAS response criteria at any point during the study. There was a statistically significant reduction in CD4؉ lymphocytes (P < 0.05), CD8؉ lymphocytes (P ‫؍‬ 0.05), and CD68؉ macrophages (P < 0.02) in the ST after 12 weeks of treatment compared with baseline. The ST and peripheral blood of those patients fulfilling the DAS response criteria contained more CD45RO؉ cells at baseline and displayed a significant reduction in these cells compared with nonresponding patients.Conclusion. The changes in ST, together with the improvement in clinical joint scores, after treatment with alefacept support the hypothesis that T cell activation plays an important role in this chronic inflammatory disease. Furthermore, since alefacept, a T cellspecific agent, led to decreased macrophage infiltration, the data indicate that T cells are highly involved in synovial inflammation in PsA.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

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Alefacept treatment in psoriatic arthritis: Reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis

Kraan

Kuijk

Dinant

et al. 2002

Arthritis & Rheumatism

135

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“…Accordingly, several components of the pathways involved in T-cell activation are well-established targets in psoriasis antibody-based therapies, for example anti-TNF-alpha, anti-LFA-1, anti-LFA-3, and more recently anti-IL-12/IL-23 [14,27]. However, recent studies acknowledge the importance of anti-inflammatory signals that counterbalance the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

Fuente

Pérez‐Gala

Bonay

et al. 2012

The Journal of Pathology

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2 ABSTRACT.We have investigated the expression and role of galectin-1 and other galectins in psoriasis and in the Th1/Th17 effector and dendritic cell responses associated with this chronic inflammatory skin condition. To determine differences between psoriasis patients and healthy donors, galectins expression was analyzed by RT-PCR assays in skin samples and specifically on epidermal and peripheral blood dendritic cells by immunofluorescence and flow cytometry.In skin of healthy donors galectins 1, 3 and 9 were expressed in a high proportion of Langerhans cells. Also, galectins were differentially expressed in peripheral blood dendritic cell subsets; galectin-1 and galectin-9 were highly expressed in peripheral myeloid dendritic cells compared with plasmacytoid dendritic cells. We found that non-lesional as well as lesional skin samples from psoriasis patients had low levels of galectin-1 at mRNA and protein level in parallel with low levels of IL-10 mRNA compared with skin from healthy patients. However, only lesional skin samples expressed high levels of

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The Demographics of Aging in the United States: Implications for Dermatology

Kosmadaki¹,

Gilchrest²

2002

Archives of Dermatology

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Treatment of Chronic Plaque Psoriasis by Selective Targeting of Memory Effector T Lymphocytes

Cited by 543 publications

References 19 publications

Alefacept treatment in psoriatic arthritis: Reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis

Alefacept treatment in psoriatic arthritis: Reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

The Demographics of Aging in the United States: Implications for Dermatology

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