Long-term survival and immunological tolerance of human epidermal allografts produced in culture.

Human epidermal cells from a small skin specimen can be grown in culture into multilayered sheets suitable for the permanent coverage of large burn wounds when used as epidermal autografts. We report here on the long-term survival of such cultured epidermal sheets used as epidermal allografts (EAG) across a major histocompatibility barrier in three nonimmunosuppressed adult patients, suffering from large chronic grafted leg ulcers, where the EAG have been placed to cover the conventional split-thickness skin autograft donor site. The absence of rejection was based upon clinical, histological, and immunopathological observation of the allografted sites at various intervals after grafting of the EAG. The identity of the epidermal cells on the grafted area with cultured cells from allogeneic donor was then established after blood substance typing by indirect immunofluorescence. Furthermore, epidermal cells from cultured sheets, but not control human cells from freshly excised normal epidermis, failed to stimulate the recipient peripheral blood cells in the mixed epidermal cell lymphocyte culture reaction, a finding that is related to the complete absence of class-II-antigen-bearing cells in cultured epidermis. This absence of T cell stimulation was noted not only on the day of grafting but throughout the follow-up. Altogether, these findings show that Langerhans cell and other class-II-antigen-bearing cell-depleted cultured epidermal allografts, are tolerated in unrelated recipients. EAG may serve as a skin substitute in patients with large wounds or burns. Since EAG may be grown continuously, the coverage of burns may not then be limited by the availability of the donor site, or by the time necessary to produce epidermal tissue in cultures.

A sequential study of histological and immunological changes in the skin after allogenic bone marrow transplantation.

Histological and immunopathological studies were performed on serial skin biopsies from thirteen recipients of allogenic and two recipients of autologous bone marrow transplants. Marked dermoepidermal infiltration with Leu 2a+ (OKT8+) phenotype cells was found in two patients with severe graft-versus-host disease, but the infiltration did not precede clinical onset of the graft-versus-host disease. Absence of Langerhans cells was noted during the early posttransplant period in recipients of both allogenic and autologous transplantation. Intercellular epidermal staining with anti-DR was observed in three cases, without relation to graft-versus-host disease.

Effects of aromatic retinoid (Ro 109359) on Langerhans' cells in lichen planus.

Retinoids are used in the treatment of lichen planus (LP) disease, but their mechanism of action remains unknown. We studied the epidermal Langerhans' cells in four patients with chronic LP, before and after treatment with aromatic retinoids. This study uses a new technique of quantification and exploits two monoclonal antibodies-OKT 6 specific for Langerhans' cells and BL 2 specific for HLA-DR antigens. Our results show an increase in the number of dendritic epidermal cells after treatment with oral retinoids. The number of OKT 6-positive cells is greater than the number of BL 2-positive (HLA-DR) cells before and after treatment.

Reactivity of anti-HLA class I polymorphic monoclonal antibodies with normal human skin.

In this work the reactivity of 16 monoclonal antibodies raised against different HLA class I specificities was tested with human skin of healthy donors of known HLA typing. By indirect immunofluorescence, six antibodies reacted strongly with keratinocytes carrying the corresponding alloantigens. The reactivity of 3 other antibodies which was weak or absent using indirect immunofluorescence, was enhanced by various amplification systems such as avidin-biotin-peroxidase method, biotin-streptavidin-fluorescein complex and especially preliminary trypsin treatment that revealed alloantigens masked in the epidermis. The immunostaining of 4 antibodies was negative regardless of the method used. Some of the antibodies we tested cross-reacted with cytoplasmic antigens of keratinocytes. This study has allowed to select a battery of monoclonal antibodies which can specifically detect alloantigens on keratinocytes and will be useful for the recognition the cell origin in allografting experiments.

[Acanthosis nigricans, hyperandrogenism, insulin resistance and mixed hyperlipemia]. / Acanthosis nigricans, hyperandrogénie, insulinorésistance et hyperlipémie mixte.

We report the case of a 22-year old woman who presented skin lesions of acanthosis nigricans, hirsutism and secondary amenorrhoea. She had high plasma levels of adrenal androgens and low plasma levels of sex steroid binding protein. Polycystic ovaries were discovered in the course of a laparotomy performed for paraovarian cyst. An oral glucose tolerance test revealed a state of hyperinsulinism with intolerance to carbohydrates, while the body mass index was normal. This insulin resistant state corresponded in vitro to a decrease in the number of erythrocyte insulin receptors without decrease in their affinity for insulin. Following paradoxical improvement during a full-term pregnancy, there was gradual deterioration of diabetes control requiring insulin therapy. This metabolic decompensation was accompanied by major hyperlipaemia followed by acute haemorrhagic pancreatitis. This case illustrates the course of a type A insulin resistance syndrome which was detected at an early stage in front of an hirsutism-acanthosis nigricans association. The underlying pathogenic mechanisms of these pathologies are discussed.

[Kaposi angiosarcoma in renal transplant recipients]. / L'angiosarcome de Kaposi chez les transplantés rénaux.

Four cases of Kaposi's sarcoma in recipients of renal transplants are reported. The 4 patients of Italian origin were male. Kaposi's sarcoma, began during pre-transplantation haemodialysis, then extended in one of the patients; in the remaining 3 patients it developed 20 months on average after transplantation. All patients were receiving an immunosuppressive treatment (azathioprine, systemic corticosteroids, anti-lymphocyte serum). Kaposi's sarcoma was located in the skin and mucosae, sometimes in lymph nodes and viscera. In 2 patients the cutaneous and mucosal lesions responded well to vindesine: in the other two patients withdrawal of the immunosuppressive therapy had no effect on the course of the disease. This study highlights the multiple factors involved in the development of Kaposi's sarcoma, notably immunosuppression and the ethnic factor.

[Antiprothrombinase type of circulating anticoagulants during acute disseminated lupus erythematosus]. / [Les anticoagulants circulants de type antiprothrombinase au cours du lupus érythémateux aigu disséminé.]

We report the observations of 4 young women suffering from SLE witha circulatig antiprothrombinase anticoagulant. Antiprothrombinase is the most frequent circulating anticoagulant found in SLE (5 to 10 p. 100). SLE is the main aetiology for antiprothrombinase (over 50 p. 100). It is called 'lupus anticoagulant'. Some symptoms seem to be more frequent in SLE with antiprothrombinase. Such are biological signs (false positive tests for syphilis. Coombs test, thrombopenia, prothrombin deficiency) and clinical signs (venous or arterial thrombosis particularly if oestroprogestative treatment is taken, bleeding if thrombocytopenia or deficiency of prothrombin; repetitive abortion and may be neuropsychiatric signs). Antiprothrombinase is an autoantibody (IgG or IgG + M) polyclonal in SLE, with antiphospholipid activity. It could decrease the production of prostacyclin (PGI2) from free arachidonic acid derived from membrane bound phospholipids. Immunological properties of antiprothrombinase could account for clinical and biological associated signs.

[Treatment of severe alopecia areata with topical applications of cyclosporin A]. / Traitement des pelades sévères par applications locales de cyclosporine A.

Cyclosporin A (CyA) is a fungal peptide used as immunosuppressor in human organ transplantation. Increased hair growth appears to be a common side-effect of treatment, occurring in almost all patients treated with oral CyA. The development of hypertrichosis during CyA administration is not hormone-dependent; it may be mediated by a direct effect of the drug on the hair growth process. We used CyA topically (5 p. 100 oily solution) in 14 patients with severe alopecia areata (totalis 5, ophiasis 3, bald plaques 6). The drug was applied on the alopecia twice a day for 5 +/- 1.5 months. Patients were examined monthly. No clinical adverse effect was observed. Routine blood examination did not show any change, except for a transient increase of hepatic enzymes in one patient. CyA determinations were performed monthly by radioimmunoassay. No CyA was detected in the patients' serum. Treatment resulted in no regrowth in 8 patients, development of vellus hair in 3 patients (alopecia areata totalis 2, ophiasis 1) at the end of therapy, and normal hair growth in 3 patients with bald plaques. We may conclude that CyA is capable of inducing regrowth of hair when applied topically. However, the drug does not seem to be useful for the treatment of alopecia areata.

[Granular-cell tumor (Abrikosov). Immunohistological study of 4 cases with review of the literature]. / Tumeur à cellules granuleuses (Abrikossoff). Etude immunohistologique de 4 cas avec revue de la littérature.

Granular-cell tumour (GCT) is a benign neoplastic proliferation first described by Abrikossoff (1), who considered it to be of muscular origin. Since then, however, the histogenesis of GCT has been a matter of serious controversy, and various cell types have been considered as being the origin of GCT. In this work we investigated the immunohistochemical profile of four cases of GCT using antibodies to several neural differentiation markers: S-100 protein, neurofilaments (NF), glial fibrillary acidic protein (GFAP). The results were compared to those obtained on three cases of schwannomas (S) and to those already reported in literature. Four cases of GCT were retrieved from the files of the Laboratory of Histopathology of the Clinic of Dermatology, Hôp. E.-Herriot. The tumours had been observed during a two-year-period (1983-1984), fixed in Bouin's fixative and embedded in paraffin. In parallel, three cases of S that were treated in the same way were also studied. This was performed on 3 mu-thick paraffin sections using the avidin-biotin-peroxidase complex method (kit Vectastain, Vector Lab., Burlingame, USA). The following antibodies were used: a) antiserum to protein S-100 (Dakopatts, Denmark) (working dilution 1: 50); b) monoclonal antibody to 200 Kd NF (Labsystem, Helsinki) (working dilution 1: 40): C) monoclonal antibody to GFAP (Biosoft, Paris) (working dilution 1: 10).(ABSTRACT TRUNCATED AT 250 WORDS)

[Severe psoriasis induced by chloroquine (nivaquine)]. / Psoriasis grave induit par la chloroquine (nivaquine).

The adverse effects of a variety of drugs on psoriasis are well documented, and they generally result in aggravation of the disease. We report the case of a 75-year old man who developed a psoriatic erythroderma and a generalized pustular psoriasis two weeks after the beginning of an antimalarial treatment. The psoriasis responded poorly to etretinate alone, and an etretinate-methotrexate combination was needed to cure the patient. Some psoriasis vulgaris plaques persisted for six months after the acute complication. Thus, chloroquine should be entered in the list of drugs which may induce psoriasis.

[Association of mycosis fungoides and Hodgkin's disease]. / Association mycosis fongoïde et maladie de Hodgkin.

A 69-year-old man developed a Hodgkin's disease 2 years after he started a mycosis fungoides. He presented cutaneous plaques of mycosis fungoides. The first signs of Hodgkin's disease was acquired ichthyosis and loss of weight. Echotomography of the abdomen showed retroperitoneal nodes. A laparotomy was performed and the histopathologic examination of the lymph nodes revealed a Hodgkin's disease type 2 (sclero-nodular). The liver and the bone marrow were involved. A chemotherapy was completed but the patient died 10 months later. The review of the literature showed 24 patients with Hodgkin's disease and mycosis fungoides or Sézary syndrome. Relation between mycosis fungoides, Hodgkin's disease and lymphomatoid papulosis are discussed.

[Cyclosporin in the treatment of bullous pemphigoid: preliminary study]. / La ciclosporine dans le traitement de la pemphigoïde bulleuse: étude préliminaire.

Bullous pemphigoid is a typical autoimmune disease. It is classically treated with systemic corticosteroids alone or combined with immunosuppressants. Cyclosporine A (CyA), a new immunosuppressive agent with high activity in organs and bone marrow transplantation, could be expected to prove effective in this disease owing to its action on lymphocytes. Seven patients with bullous pemphigoid were treated with CyA in daily doses of 6 to 8 mg/kg bodyweight. Treatment was monitored by measurements of serum CyA, creatinine and liver enzyme levels. The effectiveness of treatment was assessed on clinical changes. The seven cases are dealt with individually, with a brief case-report for each of them. The only side-effects observed were reversible rises in serum creatinine levels and hypertrichosis in two cases; these are usual reactions to the drug. Hormonal assays were normal in two female patients. Concerning results, our patients fell into two groups. Among those treated with CyA alone there were two failures and two sustained satisfactory results. Treatment was successful in all patients treated with CyA during relapses under corticosteroid therapy, but two patients relapsed after CyA was discontinued. It is concluded that CyA is of no interest in the acute phase of bullous pemphigoid, that the long-term stability of the results obtained is doubtful and that this potentially nephrotoxic drug should be avoided or administered with extreme caution in elderly people, since their renal function may be at the limit of normality.

[Lichen planus. Study of the T-lymphocyte population and Langerhans cells using monoclonal antibodies]. / Liquen plano. Estudio de la población linfocitaria T y células de Langerhans a través de los anticuerpos monoclonales.

The purpose of the present study was to examine the phenotype of the immunocompetent cells in cutaneous infiltrates and peripheral blood in Lichen Planus. 14 patients have been studied using Monoclonal Antibodies directed against T cell populations. We have used in this study the indirect immunofluorescence technique. Helper cells (OKT4+) and Suppressor/cytotoxic cells (OKT8+) have been observed in all cutaneous infiltrates, and numerous Langerhans cells identified by OKT6 in epidermis and dermis. In peripheral blood, the balance between the two major T cell subsets (OKT4+ and OKT8+) was increased by a reduction of the percentage of Suppressor/cytotoxic cells. This balance is statistically significant (P 0,02). Our results confirm the existence of a lymphocytotoxic process in Lichen Planus.