Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis-0

<p><b>Copyright information:</b></p><p>Taken from "Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis"</p><p>http://www.translational-medicine.com/content/5/1/27</p><p>Journal of Translational Medicine 2007;5():27-27.</p><p>Published online 7 Jun 2007</p><p>PMCID:PMC1906741.</p><p></p

Clinical photographs of two representative patients with disease relapse upon cessation of efalizumab treatment.

<p>(<b>A</b>) Baseline lesions (left), response to efalizumab (center) and a marked erythematous psoriatic reaction 5 weeks after ceasing treatment (right). (<b>B</b>) Baseline photographs showing upper leg psoriatic plaques (left) which responded to efalizumab at week 12 (center) and a relapse in the same location (right). Note the inflammatory nature of the lesions during relapse.</p

Genomic characterization of relapsed psoriasis lesions.

<p>(<b>A</b>) Venn diagram showing DEGs for different comparisons, week 12 versus LS; week 12 versus relapse; relapse versus LS. There were no unique DEGs in relapse compared to LS skin. (<b>B</b>) Scatter plot showing an excellent correlation between the “treatment effect” and “relapse effect”. (<b>C</b>) Number of genes improved by treatment and reversed by relapse. Red blocks were increased DEGs, green blocks were decreased DEGs.</p

GSEA analysis of published gene sets.

a<p>Size, number of genes in gene set.</p>b<p>ES, enrichment score.</p>c<p>NES, normalized enrichment score.</p>d<p>CS, connectivity score.</p>e<p>REF, reference for gene set.</p

Increased inflammatory myeloid DCs in relapsed lesions.

<p>(<b>A</b>) Representative immunohistochemistry and (<b>B</b>) counts of CD11c⁺ cells per mm in non-lesional skin (NL), lesional skin (LS), and in the index lesional plaque at weeks 2, 6 and 12 and time of disease relapse. (<b>C</b>) The numbers of CD1c⁺ cells did not change with treatment or relapse. (<b>D</b>) CD83⁺ mature DCs followed the same pattern as CD11c⁺ DCs. (<b>E</b>) There were many inflammatory myeloid DCs in the relapsed lesions, shown by immunofluorescence as CD11c⁺ cells (red) that were not co-expressing CD1c (and thus were not yellow), and (<b>F</b>) quantified as CD11c⁺ minus CD1c⁺ cells. (<b>G</b>) Inflammatory CD11c⁺ DCs were co-expressing TNFSF10/TRAIL. (<b>H</b>) TNF- and iNOS-producing DCs (TIP-DCs) were found in relapsed lesions. CD11c⁺ cells (red) co-expressing (<b>I</b>) CD14 and (<b>J</b>) CD16 (both green). Cells that co-express the two markers in a similar location are yellow in color. A white line denotes the dermo-epidermal junction. Bar is 100 µm.</p

Enrollment flowchart.

<p>Enrollment flowchart.</p

Clinical and histological response to efalizumab and during relapse.

<p>(<b>A</b>) Mean PASI scores, (<b>B</b>) circulating absolute lymphocyte count, (<b>C</b>) epidermal thickness (µm), (all n = 8) and (<b>D</b>) normalized keratin 16 (K16) mRNA expression (n = 4), throughout the trial and at time of relapse. Non-lesional (NL) and lesional skin (LS), error bars represent the standard error of the mean. ^* p<0.05; ^** p<0.01; ^*** p<0.001. Representative (<b>E</b>) haematoxylin and eosin (H&E), (<b>F</b>) K16 protein, (<b>G</b>) neutrophil elastase, (<b>H</b>) CD3⁺ T cell immunohistochemistry, and (<b>I</b>) CD3⁺ T cell counts, showing the psoriasiform nature of the relapse lesion, with characteristic K16 staining, neutrophils and CD3⁺ T cells. Bar is 100 µm.</p