Development of concepts of etiology, pathogenesis and treatment of pemphigus vulgaris based on the hypothesis of atavistic origin of the disease.

Atavistically dependent expression of pemphigus vulgaris 'immune' antigen (PVIA) on the human epidermocyte surface is hypothetically the key factor of autoimmune aggression onset in pemphigus patients. Normal epidermocytes can express PVIA in response to a putative factor of 'sheding' as well as to certain biologic, chemical and physical effects. Taking into account the fact that the antibodies against 'shedding' factor carry out the function of anti-idiotypic ones, they can be used as blocking antibodies in treatment of pemphigus vulgaris.

Pemphigus antibodies and shedding snake serum enhance susceptibility of epidermal keratinocytes in natural cytotoxic reactions.

In order to clarify the role of natural cytotoxicity (NC) in the damage of epidermal keratinocytes (EK) in pemphigus vulgaris (PV) we used the direct 51Cr-release assay in studying the cytotoxic activity of large grandular lymphocytes (LGL), obtained from 34 acute PV patients and 19 healthy donors against EK of PV patients, donors, intact newborn BALB/c mice and mice with experimental PV, shedding and non-shedding grass snakes. We also investigated the effect of pemphigus antibodies and shedding snake serum protein (SSSP) upon EK sensitivity to cytotoxic effects of NC effectors. In other experiments, studied were the amount of serine proteinase secreted by donor LGL in the presence of membrane antigen of antibody- or SSSP-transformed EK, and direct effect of pemphigus antibodies and SSSP upon the release of radioactive label and endoproteinases from EK.

Stimulating effect of pemphigus antibodies upon interleukin inhibitor production by normal human epidermocytes.

The present study deals with the effect of pemphigus antibodies upon immunoregulatory activity of normal human keratinocytes. In vitro experiments were carried out to determine the effect of epidermal keratinocyte culture supernatants (EKCS) upon the ability of peripheral blood mononuclear cells from healthy subjects to give lymphoproliferative response to lectins, and to induce production of interleukin I and interleukin 2 activity, and exogenous interleukin 2 absorption. It was found that EKCS, obtained in response to epidermal keratinocyte cultivation in the presence of I mg/ml pemphigus antibodies, inhibit both interleukin cascade reactions and mitogen-induced lymphoproliferative response.

The effect of experimental haemocarbofiltration upon activity of mononuclear cells from normal and autoimmune patients.

We examined the functional activity of peripheral blood mononuclears (PBM) of 18 healthy subjects, 18 patients with pemphigus vulgaris, 12 with bullous pemphigoid and nine with discoid lupus erythematosus, after haemofiltration on carbon haemo-adsorbents of 'SKN' type. Proliferation in the response to PHA and Con A, for IL-1 and IL-2 production, and exogenous IL-2 absorption were assayed. The presence of IL-1 and IL-2 inhibitors in haemocarbo-adsorbent eluants was shown.

Cytotoxic proteases in blister fluid of pemphigus and pemphigoid patients.

Investigation of blister fluid (BF) from 49 pemphigus vulgaris and 27 bullous pemphigoid patients revealed direct interrelation between proteolytic and cytotoxic activities of BF. Human epidermal keratinocytes proved to be more sensitive to the cytolytic effect of BF as compared to human endotheliocytes and fibroplasts. Epidermal keratinocyte cultivation in patients' BF led to proteolytic activity enhancement in culture supernatant.

Fixation of pemphigus vulgaris and foliaceus antibodies in shedding snake epidermis.

The fixation of pemphigus antibodies was revealed by indirect immunofluorescence in shedding grass snake epidermis. The antibodies of patients with pemphigus vulgaris (PV) were specifically binding to the antigenic substance which appears in the snake epidermis at the initial stage of integument change. At the peak of shedding, the fixation of PV antibodies was observed only in the upper layers of the 'old' epidermis, although the intensity of fluorescent staining was considerably reduced.

Autoreactive cytotoxic T lymphocytes in pemphigus and pemphigoid.

In order to know whether effector cells are capable of recognizing the epidermal targets in pemphigus vulgaris (PV) and bullous pemphigoid (BP), non-adherent cells (NAC) of peripheral blood from 27 primary PV, 19 BP patients and 12 healthy volunteers were used in cytotoxic tests. Autologous, allogenic and murine epidermal keratinocytes as well as autologous and allogenic fibroblasts were employed as targets. Total esterase activity of serine proteinases was measured in supernatants of samples and the results obtained were compared with the data received in 51Cr-release assay.

Interleukin cascade reaction inhibition by supernatants of the cultures of antibody-transformed human basal keratinocytes.

We investigated the ability of normal human basal keratinocytes, treated with antibodies against basal keratinocytes, to produce an effect upon the activity of allogenic peripheral blood mononuclear cells. We determined the influence of basal keratinocyte culture supernatants (BKCS) upon the mononuclear cell ability for proliferation in the response to PHA and Con A, for IL 1 and IL 2 production as well as for absorption of exogenous IL 2. It was found that BKCS inhibit the lectin-dependent transformation of mononuclears and interleukin cascade reactions.