PMC1208875_01
Clinical photos of patient 1 during the flare reaction in June 2004 (upper panels), with follow-up photos after standard-dose treatment with efalizumab for three months (lower panels).
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F1
However, he missed a dose in June 2004 and his skin flared again, so he re-attended our clinic (Fig 1).
FACS analysis of peripheral blood lymphocytes (gated) of patient 1, pre-treatment (A) and during flare (B). Isotype (Becton Dickenson) is shaded, solid line shows T cell binding of efalizumab-FITC (custom design, Genetech), and dotted line shows binding of an anti-CD11a antibody which binds to a different epitope (clone 25.3, Immunotech). The pre-treatment sample (A) shows high-level binding of both anti-CD11a antibodies. The sample acquired during flare (B) shows the ex-vivo level of binding of efalizumab-FITC is the same as isotype, as there is already saturation of this CD11a epitope by therapeutic administration of efalizumab. There is also reduced binding of the 25.3 epitope indicating significant down-regulation of CD11a surface expression.
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F2
Despite missing a dose, there was still leukocyte CD11a saturation by efalizumab (Fig. 2B, solid line identical to isotype, shaded).
Immunohistochemistry of lesional skin biopsies during psoriatic flare of patient 1 and 2, showing similar features (magnification x 10). Haematoxylin and eosin (H&E) stain showing epidermal hyperplasia, elongation of rete ridges, dilatation of dermal papilla blood vessels, and mononuclear and neutrophil leukocyte infiltration. Some CD3 (BD) T cells infiltrate the dermis and epidermis, and these are mostly CD8+ (BD Pharmingen), although there are less T cells than during untreated psoriasis. Most of the epidermal T cells are CD103+ (Biodesign, Kennebunnk, ME). CD11c+ (BD Pharmingen) and iNOS+ (R&D Systems) cells are dramatically increased compared to non-lesional skin, and stain in a dendritic pattern.
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F3
Immunohistochemistry at this time (Fig. 3) shows similar results to patient 1: there are relatively reduced CD3+ and CD8+ cells, epidermal T cells are CD103+, and there are abundant CD11c+ and iNOS+ inflammatory cells infiltrating the dermis and epidermis.
PMC1208875_02
Immunohistochemistry of lesional skin biopsies during psoriatic flare of patient 1 and 2, showing similar features (magnification x 10). Haematoxylin and eosin (H&E) stain showing epidermal hyperplasia, elongation of rete ridges, dilatation of dermal papilla blood vessels, and mononuclear and neutrophil leukocyte infiltration. Some CD3 (BD) T cells infiltrate the dermis and epidermis, and these are mostly CD8+ (BD Pharmingen), although there are less T cells than during untreated psoriasis. Most of the epidermal T cells are CD103+ (Biodesign, Kennebunnk, ME). CD11c+ (BD Pharmingen) and iNOS+ (R&D Systems) cells are dramatically increased compared to non-lesional skin, and stain in a dendritic pattern.
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F3
Immunohistochemistry at this time (Fig. 3) shows similar results to patient 1: there are relatively reduced CD3+ and CD8+ cells, epidermal T cells are CD103+, and there are abundant CD11c+ and iNOS+ inflammatory cells infiltrating the dermis and epidermis.