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Background An increasing number of patients with severe psoriasis are failing to respond to antitumour necrosis factor (TNF)-α therapy (etanercept, infliximab and adalimumab). Objectives We observed that many of these patients developed antinuclear antibodies (ANA) and antidouble-stranded DNA (anti-dsDNA) antibodies while on treatment prompting us to investigate whether their development is associated with anti-TNF treatment failure. Methods All patients with psoriasis who had received anti-TNF therapies were identified and their blood results and treatment histories were obtained from electronic patient records and case notes. Results A total of 97 patients had been treated with anti-TNF agents (60 were on their first agent, 22 had been on and stopped one agent, nine had been on and stopped two agents and six had been on and stopped all three agents). ANA developed in 17% of patients on their first treatment, 54% of patients who had failed one treatment, 78% of patients who had failed two treatments and 83% of patients who had failed all three treatments. Anti-dsDNA antibodies developed in 2%, 27%, 33% and 83% of patients from the same respective groups. Significantly, the antibodies developed before treatment had failed with all three agents and their development was not related to the total time that patients had been on anti-TNF therapy. Conclusions This study suggests that the development of ANA and anti-dsDNA antibodies on anti-TNF treatment may act as a marker of forthcoming treatment failure. Large-scale prospective studies are required to assess the importance of this observation. [ABSTRACT FROM AUTHOR]

Tissue from the acute, non-infected eruption of sixteen atopic eczema subjects was subjected to an indirect immunoperoxidase technique using monoclonal antibodies recognizing T-lymphocyte subsets, Langerhans cells and natural killer cells. Over half the cells infiltrating the dermis were T lymphocytes, including a large majority of helper T cells and relatively few suppressor T cells. Langerhans cells were present in significant proportions in the dermis and probably reflected increased antigen presentation within the affected skin. There was no evidence of increased natural killer cell presence. This study suggests that type IV hypersensitivity may be implicated in the aetiology of atopic eczema. [ABSTRACT FROM AUTHOR]

Cellular adhesion molecules play a central role in leucocyte migration through peripheral blood and tissues. A crucial stage in these events is selectin-mediated adhesion involving E-selectin expressed on activated endothelium interacting with a range of carbohydrate ligands expressed by specific subpopulations of leucocytes. As such mechanisms may be relevant to bone marrow-derived dendritic epidermal Langerhans' cell (LC) migration, expression of these carbohydrate ligands was assessed immunocytochemically in whole skin biopsies and in epidermal cell suspensions obtained from adult humans. Double-labelling experiments revealed that sialyl Lewis x, recognized by the monoclonal antibody CSLEX1, was expressed on epidermal LC (n = 9). Furthermore, expression was enhanced at 24 hr following epicutaneous application of antigen and in the inflammatory disorder psoriasis (n = 10). E-selectin was concomitantly strongly expressed on dermal endothelium in psoriasis and allergic contact dermatitis. Intradermal injection of the T-cell-derived cytokine interferon-γ, (IFN-γ) led to increased LC expression of sialyl Lewis x. In epidermal cell suspensions, in contrast to keratinocytes, CD1a+ cells expressed sialyl Lewis x, in tensity of which was enhanced after 4 days in culture. CSLEX1 staining could be abolished and CD115 (non-sialated Lewis x) expression induced by saponification and treatment with neuraminidase. Expression of other selectin ligands was also examined. While the cutaneous lymphocyte antigen defined by the monoclonal antibody HECA-452 reacted with a small minority of LC, sialyl Lewis a and sulphatide were not expressed under any experimental conditions. These studies indicate that E-selectin-sialyl Lewis x interactions are potentially important in LC migration, both into and out of skin. [ABSTRACT FROM AUTHOR]

In a study of the direct effects of interferon-gamma (IFN-γ) on normal human skin, healthy adult male volunteers received either 3 μg (n = 4) or 30 μg (n=9) of recombinant IFN-γ administered intradermally over 3 days. Biopsies were taken on day 6 and histopathological examination of fixed paraffin-embedded sections from sites which had received 30 μg IFN-γ revealed a moderate perivascular lymphohistiocytic dermal infiltrate with mast cells. Immuno- phenotyping of 5 μm cryostat sections demonstrated that 3 μg IFN-γ induced keratinocyte HLA-DR expression in the absence of any significant infiltrate. More intense keratinocyte HLA-DR expression was produced by 30 μg IFN-γ in all specimens, with HLA-DP concurrently expressed in three biopsies. The ratio of CD4:CD8 cells within the infiltrate was approximately 3:I. CDI+ cells within the epidermis were markedly depleted by 30 μg IFN-γ, while CDI-labelled cells were observed in the dermal perivascular infiltrate. Intradermal IFN-γ induces similar immunopathological changes to those observed in many of the inflammatory dermatoses. [ABSTRACT FROM AUTHOR]

Keratinocyte expression of the monocyte/macrophage surface antigens defined by OKMI and OKM5 antibodies (Ortho Diagnostics) was examined using the peroxidase anti-peroxidase immunohistochcmical technique. A range of inflammatory cutaneous disorders were investigated, including lichen planus, psoriasis and atopic dermatitis. Positive suprabasal keratinocyte expression of OKM5 antigen was observed in all disorders, while keratinocyte staining with OKMI antibody was consistently negative. These results provide further evidence that keratinocytes may play an important role in cutaneous immune responses. Furthermore, they are consistent with the recent observation that HLA-DR positive keratinocytes may modulate cutaneous immunological reactions by inducing T-cell unresponsiveness. [ABSTRACT FROM AUTHOR]

Immunogold-silver staining (IGSS) was evaluated for the localization of eutaneous antigens in frozen and paraffin-embedded tissue, employing antibodies to a variety of intracellular, cell-surface and extracellular epitopes in an indirect immunogold reaction, followed by silver enhancement. The principal advantages of IGSS are the avoidance of toxic reagents and the production of a silver precipitate that is permanent, clearly visible and of sufficient contrast with the reaction products of alternative immunolocalizing techniques to be of value in double-labelling procedures. It seems to localize antigenic determinants well, but does not appear to be particularly sensitive, especially for the demonstration of antibodies to extracellular constituents. Limitations of IGSS include the propensity to non-specific staining, and the need to vary the duration of the development stage during silver enhancement. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about expression of the myelomonocytic antigens in human epidermis.