Immunohistochemical study on the pattern of 50 kd cytokeratin in psoriasis.

Three biopsies of normal skin and 15 biopsies collected from patients with psoriasis vulgaris were analyzed for the expression of the 50 kd cytokeratin using direct immunofluorescence and ABC technique before and after local treatment with anthralin 0.1% in a petrolatum base, with 0.05% betamethasone dipropionate cream, and finally, after PUVA treatment. Antiserum against the 50 kd anti-cytokeratin reacted with tissue sections of normal skin, staining cells in the basal layer, while the psoriatic skin sections before the various treatments showed a staining concerning the whole thickness of the epidermis. After the various therapies, the 50 kd cytokeratin immunoreactivity was observed only in the basal layer of those psoriatic skin sections that showed complete clinical clearing, while it was observed in the whole thickness of psoriatic patches that did not clear. These data suggest that the normalization of the 50 kd cytokeratin expression pattern can be considered as a marker of clinical remission of psoriasis.

The role of plasminogen activators in alopecia areata.

Plasminogen activators are serine proteinases which transform the serum zymogen, plasminogen, into plasmin, a broad-spectrum protease with fibrinolytic effect. Two main plasminogen activators have been described in humans: urokinase (UK; molecular weight, 55,000) and tissue-type plasminogen activator (tPA; molecular weight, 74,000). Thirteen subjects were studied who had alopecia areata (AA), nine in the active phase and four in remission. There were alterations in the perivascular and peribulbar fibrinolytic activity in the nine subjects in the active phase of disease, suggesting a possible role of plasminogen activators in AA. A modified Todd's autohistographic method was used to evaluate cutaneous fibrinolytic activity (which depended on the activity of plasminogen activators) in the 13 AA subjects and five volunteer controls. Cutaneous fibrinolytic activity was reduced in perivascular areas, but increased in peribulbar areas, in the nine subjects in the active phase of disease. Tests with monoclonal antibodies directed against the catalytic sites of tPA and UK showed that the perivascular fibrinolytic activity was tPA dependent, and the peribulbar fibrinolytic activity was UK dependent.

Antipsoriatic therapies inhibit epidermal plasminogen activator activity.

Urokinase (UK, Mr 55,000) and tissue-type plasminogen activator (tPA, Mr 74,000) are serine proteinases involved in many biological processes, ie, cell migration, neoplastic transformation, and extracellular proteolysis. Cutaneous fibrinolytic activity (dependent on the activity of UK and tPA) was studied with the autohistographic fibrin film method in 40 patients affected by psoriasis vulgaris before and after topical (anthralin, betamethasone valerate, hydrocolloid occlusive dressing) or systemic psoralen-ultraviolet-light (PUVA) treatments. Autohistographic studies also were performed after apposition of monoclonal antibodies directed against the catalytic site of UK and tPA. Finally, UK and tPA were localized immunohistochemically in the psoriatic plaques and in controls using the immunoperoxidase procedure based on the biotin/avidin system. UK and tPA immunoreactivity was present in the cytoplasm and around the outlines of keratinocytes in the psoriatic patches before treatment and in the patches not cleared after treatment, while it was not detectable in normal epidermis, in the unaffected psoriatic epidermis, and in the cleared psoriatic skin. Cutaneous fibrinolytic activity was present in the cases in which UK and tPA were detected histochemically and, in the psoriatic epidermis, it was abolished by preincubation with anti-tPA but not with anti-UK antibodies. This study suggests that established topical and systemic treatments for psoriasis possess UK and tPA antagonist activity.

[Study of filaggrin in psoriasis]. / Studio della filaggrina nella psoriasi.

Filaggrin is a histidine-rich basic protein that aggregates keratin filaments in fully differentiated cells of the epidermis. Filaggrin is synthesized in the granular cell layer as a high-Mr phosphorylated precursor, profilaggrin, that is processed to form the lower-Mr product present in cornified cells. The catabolism of filaggrin in stratum corneum produces urocanic acid and carboxylic-pyrrolidone acid that, respectively, absorb UV radiations and support cutaneous hydratation. In this study we evaluated by direct-immunofluorescence and by immunoperoxidase staining using rabbit antihuman filaggrin antiserum localization of filaggrin in psoriatic skin and in normal human skin before and after treatment with anthralin 0.1%, betamethasone 0.05% and hydrocolloid dressing. Antiserum against human filaggrin reacted with tissue sections of normal human skin, staining cells in the granular layer and in the stratum corneum, while no staining of human psoriatic skin sections was observed. After treatments, filaggrin resulted present in those psoriatic skin sections that showed complete clinical remission, while it was not observed in psoriatic patches which did not clear. These studies suggest that human skin filaggrin can be considered a marker of clinical remission of psoriasis.