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Biomedical subjects

J F Nicolas

Publications and source records attributed to J F Nicolas.

At least 73 records · Page 4Linked to original sources
PubMed1994

Human monoclonal autoantibodies specific for the bullous pemphigoid antigen 1 (BPAg 1).

Bullous pemphigoid (BP) is an acquired blistering skin disease associated with the production of IgG autoantibodies to the 230-kDa BP Ag (BPAg1). To better characterize the epitopes of BPAg1, we generated immortalized B cell lines secreting human mAbs (HumAbs) to BPAg1 from two BP patients whose sera reacted with native BPAg1 but not with a recombinant BP55 carboxyl-terminal peptide. Ab-producing B cell lines were established by EBV infection of CD40-activated PBMCs. Three independent clonal lines were obtained that secreted IgG HumAbs, including one IgG1 kappa (BP3) and two distinct IgG4 kappa (BP1 and BP2). These three HumAbs immunoprecipitated BPAg1. Blocking immunofluorescence experiments and phylogenetic studies showed that these Abs recognize different epitopes of BPAg1. This analysis with HumAbs further extends the serologic demonstration of the wide variety of epitopes recognized by BPAg1 autoantibodies which contrasts with the limited number of epitopes recognized by thyroid peroxidase monoclonal autoantibodies.

Antibodies, Monoclonal↗
PubMed1994

Establishment of nickel-specific T cell lines from patients with allergic contact dermatitis: comparison of different protocols.

Allergic contact dermatitis is a delayed-type hypersensitivity reaction, secondary to hapten-specific T lymphocyte activation in sensitized individuals. The present study reports on the establishment of T cell lines from peripheral blood mononuclear cells (PBMC) of nickel-allergic patients, initially cultured with nickel, IL-2, or PHA and IL-2. It was possible to derive hapten-specific T cell lines from the three protocols, and the best proliferative responses to nickel were observed when PBMC were cultured in the presence of nickel in vitro. T cell lines initially cultured with IL-2 always gave better specific proliferative responses to nickel than those derived with PHA and IL-2. Phenotypical analysis of the nickel-specific T cell lines showed that they were mainly composed of activated CD8+ TcR alpha beta + T lymphocytes. These results emphasize the importance of initial culture conditions for the generation of hapten-specific T cell lines and suggest that CD8+ lymphocytes could play an important role in the pathogenesis of allergic contact dermatitis.

CD4-CD8 Ratio↗
PubMed1994

Comparative study of indirect immunofluorescence and immunoblotting for the diagnosis of autoimmune pemphigus.

The diagnosis of pemphigus relies on immunopathological criteria including the detection of circulating autoantibodies to desmosomal components. In the present work we compared the usefulness of immunoblotting (IB) and indirect immunofluorescence (IIF) in the diagnosis of pemphigus using monkey oesophagus (MO) and rabbit lip (RL) as epithelial substrates. Among 54 sera from patients with well-documented pemphigus (40 pemphigus vulgaris, PV, and 14 pemphigus foliaceus, PF), 46 (85%) proved positive by IIF (46 on MO and 41 on RL) as compared with 44 (81.5%) positive by IB. IIF and IB were equally sensitive (90%) for the diagnosis of PV whereas IIF (on RL) was more sensitive (71%) than IB (57%) for the detection of PF autoantibodies. However, when the two techniques were considered in combination, the sensitivity of the detection of pemphigus autoantibodies rose to 94.5%. An IB study would therefore be warranted in the presence of an (alleged) pemphigus serum that was IIF-negative since approximately 10% of these were found to be positive. Furthermore, the pattern of IB reactivity may assist in classification, since the 130- and the 160-kDa antigens seem specifically correlated with PV and PF, respectively.

Adult↗
PubMed1994

The effect of anti-CD4 monoclonal antibody treatment on immunopathological changes in psoriatic skin.

Recent clinical studies which showed the therapeutic effect of cyclosporin A and of anti-CD4 MoAb emphasized the role of activated CD4+ T cells infiltrating the lesional skin in the pathogenesis of psoriasis. The aim of the present study was to analyze the mode of action of anti-CD4 MoAb in 3 psoriatic patients who experienced an anti-CD4 MoAb-induced clinical improvement maximal 3-4 weeks after the onset of an 8-day therapy. We evaluated the effect of anti-CD4 MoAb treatment on the phenotype of resident and passenger inflammatory skin cells in lesional skin samples. We observed a gradual improvement of 3 out of 4 histopathologic features including parakeratosis, papillomatosis and acanthosis. In the dermis there was no modification in the density of the dermal mononuclear cell infiltrate, which consisted mainly of CD3+, CD45RO+, TCR alpha beta+, CD11a+, HLA-DR+T cells with a CD4/CD8 cell ratio of 1.5/1. Therefore as previously observed for peripheral blood mononuclear cells, the number of CD4+ T cells infiltrating the dermis remained unaffected by the treatment. In contrast, CD4 MoAb treatment was associated with drastic changes in the epidermis. These included a decrease in both CD4+ and CD8+ epidermal T cell infiltrate, diminished numbers of ICAM-1+ and HLA-DR+ keratinocytes and restored numbers of CD1a+ epidermal Langerhans cells. We conclude from this study that clinical improvement of psoriasis by anti-CD4 MoAb therapy paralleled: (1) a decrease in epidermal T cells, and (2) a down-regulation of keratinocyte activation markers (ICAM-1 and HLA-DR). These results suggest that the observed changes are secondary to down-regulation of inflammatory cytokine production by T cells in situ.

Adult↗
PubMed1994

Linear IgA bullous dermatosis with autoantibodies to a 290 kd antigen of anchoring fibrils.

We describe a patient with a papulovesicular eruption associated with scarring and severe mucosal lesions that led to blindness. Direct immunofluorescence showed linear IgA deposits at the dermoepidermal junction. Indirect immunofluorescence microscopy showed that the patient's serum reacted with the dermal side of salt-split skin. Direct immunoelectron microscopy showed the IgA deposits to be associated with anchoring fibrils, whereas with Western blot analysis the patient's serum reacted with a 290 kd dermal antigen. On the basis of these findings, we suggest that our case may represent a form of IgA-mediated epidermolysis bullosa acquisita.

Adult↗
PubMed1994

Disseminated superficial porokeratosis in a patient with AIDS.

We report the case of a 50-year-old male homosexual suffering from AIDS, who developed diffuse annular hyperkeratotic lesions on the arms and legs. Histopathological examination revealed typical features of porokeratosis, which clinically was of the disseminated superficial type. Ultrastructural examination showed a paucity of keratohyalin granules and lamellar bodies. Immunohistochemical studies showed an almost complete absence of Langerhans cells in lesional epidermis. Involucrin and filaggrin expression were altered in areas of cornoid lamella formation, whereas basal keratinocytes in these areas expressed PCNA/cyclin and, to a lesser degree, p53 protein. Porokeratosis may affect immunocompetent patients, but has also been reported in the setting of immunosuppression following organ transplantation. As far as we are aware, the development of porokeratosis during the course of HIV infection has not been reported previously.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Optimization of the mouse ear swelling test for in vivo and in vitro studies of weak contact sensitizers.

Murine models for the assessment of the contact sensitizing properties of chemicals rely on mouse ear swelling tests (Mest), which are not sensitive enough to detect weak sensitizers. The aim of the present study was to develop in mice an adjuvant-free Mest appropriate for in vivo detection of any type of sensitizer (weak to strong), and useful for in vitro assessment of contact sensitivity (CS). 3 haptens were tested: dinitrochlorobenzene (DNCB), para-phenylenediamine (pPD) and isoeugenol. We compared various protocols for induction of the CS reaction, differing by the site of induction, the number of applications and the concentrations of the 3 haptens. Comparison of the induction site for optimal CS reaction showed that, in Balb/c mice, the back was a better site of induction than the abdomen. Detection of the sensitizing properties of weak sensitizers (pPD, isoeugenol) was possible using an adjuvant-free protocol, provided that the induction phase comprised hapten applications on 3 consecutive days on the backs of animals. For DNCB, one application was sufficient to obtain optimal CS reaction. For all 3 haptens, a secondary response in vitro was obtained using semi-purified lymph node T cells from animals sensitized 5 days before with the optimized Mest. These results demonstrate that the Mest could be a useful experimental model for the study of all types of contact sensitizers.

Animals↗
PubMed1994

Immunohistopathological study of autoimmune pemphigus. Lack of strictly specific histological and indirect immunofluorescence criteria for paraneoplastic pemphigus.

Paraneoplastic pemphigus (PNP) is a form of pemphigus considered to bear characteristic immunohistopathological features (vacuolar-interface dermatitis, keratinocyte dyskeratosis and reactivity of patients' sera with transitional epithelia). The present study was undertaken in order to investigate whether these criteria are specific enough so as to allow the diagnosis of PNP in the absence of clinical data. A retrospective study of 66 biopsies of pemphigus revealed that one third of them comprised histological signs of PNP; one of the corresponding sera reacted with mouse bladder epithelium. However, no evidence of a neoplastic disease was present in any of the patients, and Western blotting further excluded the diagnosis of PNP. These results suggest that some of the features considered characteristic of PNP are not strictly specific for this variety of pemphigus; hence this diagnosis cannot be reliably established by histology or immunofluorescence but requires biochemical studies.

Acantholysis↗
PubMed1994

[The desmosome: structure, function and acquired pathology].

The essential function of the skin is that of a barriere against the outside. The epidermis is the tissue which assures the solidity and the resistance of the skin against forces of traction. The desmosomes, allowing the adhesion of epidermal cells, the keratinocytes, between them, are the structures of resistance of the epidermis. This adhesion function is possible thanks to the interactions between the desmosomial molecules and cytosqueletal filaments. Currently fifteen desmosomal proteins implicated in this process have been characterized. The role of desmosome in integrity of epidermis is demonstrated by the existence of the auto immune dermatosis, the pemphigus, in which the inflammatory reaction against desmosomal proteins results in the loss of the cohesion of keratinocytes.

Cytoskeletal Proteins↗
PubMed1994

The yeast I-Sce I meganuclease induces site-directed chromosomal recombination in mammalian cells.

Double-strand breaks in genomic DNA stimulate recombination. Until now it was not possible to induce in vivo site-directed double-strand breaks in a mammalian chromosomal target. In this article we describe the use of I-Sce I meganuclease, a very rare cutter yeast endonuclease, to induce site-directed double-strand breaks mediated recombination. The results demonstrate the potential of the I-Sce I system for chromosome manipulation in mammalian cells.

Animals↗