Epidermal-binding circulating antibodies in epidermolysis bullosa acquisita: what are they?
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Biomedical subjects
Publications and source records attributed to A Claudy.
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Atopic dermatitis is a pruritic inflammatory skin disorder, involving immunological and non-immunological factors. Substance P seems to be involved in the pathogenesis of atopic dermatitis. Substance P-containing nerve fibers are increased in the lesional skin of patients with atopic dermatitis and a reduced weal and flare reaction to intradermal injection of substance P has been observed. We investigated the distribution of substance P receptors in the involved skin of patients before and after single or repetitive UVA irradiations. Our results indicate that substance P receptors of the NK-1 subtype are expressed on blood vessels and on epidermal keratinocytes of involved skin of patients with atopic dermatitis. UVA irradiations did not modify the epidermal distribution of substance P receptors but decreased their expression intensity on blood vessels. UVA irradiations seem to decrease skin inflammation through the modulation of NK-1 receptor expression on endothelial cells.
The Thomsen-Friedenreich (T) antigen is the core disaccharide of cancer-associated carbohydrates, whose expression allegedly correlates with the prognosis of some carcinomas. We studied the expression of the T antigen and its precursor (Tn) with monoclonal antibodies in formalin-fixed specimens of normal skin and various benign cutaneous tumours and inflammatory lesions (n: 105). In normal skin, both antigens were consistently expressed within the cytoplasm of mature sebocytes and rarely over the luminal surface of secretory sweat gland cells. All (21/21) sebaceous tumours showed strong T/Tn positivity; several (9/16) sweat-gland tumours were also immunoreactive, although more weakly. Pilar (n = 11), non-adnexal tumours (n = 45) and inflammatory lesions (n = 12) were as a rule unreactive. These results suggest that the T antigen is a sensitive marker of sebaceous differentiation that can be used for the study of adnexal skin tumours in routinely processed tissue specimens.
AIM: To study the immunohistochemical expression of the Thomsen-Friedenreich antigen (T) and its precursor, Tn, in the skin in various cancers. METHODS: T and Tn antigens were studied with monoclonal antibodies in 91 primary premalignant and malignant lesions, 13 cases of Paget's disease, and 26 carcinomas metastatic to the skin. The material had been collected over a 10 year period, formalin fixed, and paraffin embedded. Diagnoses had been made after examination of standard histological sections, supplemented when needed by appropriate immunohistochemical staining. RESULTS: 21% and 29% of the primary cutaneous premalignant and malignant epithelial tumours expressed the Tn and T antigens, respectively. By contrast, 81% of metastatic carcinomas to the skin were Tn positive, while only 23% of them expressed the T antigen. All cases of Paget's disease were Tn positive but only 15% of them expressed the T antigen. The 21 nonepithelial tumours (including melanomas) were as a rule unreactive. CONCLUSIONS: The accumulation of the precursor (Tn) antigen in tumours metastasising to the skin highlights the incomplete glycosylation of carbohydrate antigens occurring in these tumours. The predominant Tn versus T antigen expression appears to be a useful immunohistochemical feature which may aid in the differentiation of primary cutaneous carcinomas from metastatic tumours.
BACKGROUND: Merkel cells are neuro-endocrine cells present in the basal layer of the human epidermis and the outer root sheath of hair follicles. OBJECTIVE AND METHOD: In order to gain further insight into the as yet ill-defined involvement of Merkel cells in skin diseases, we studied the distribution of these cells in formalin-fixed, paraffin-embedded sections of 165 inflammatory, hyperplastic or tumoral skin lesions of various anatomic locations, with a monoclonal antibody to keratin 20. RESULTS: Lesions with frequently increased Merkel Cell numbers included actinic keratosis, fibrous papules of the face and some conditions with (immature) hair follicle differentiation. CONCLUSION: These results suggest that Merkel cell hyperplasia is unrelated to epidermal proliferation but that it is rather specific to a limited number of skin diseases.
Dermatofibrosarcoma protuberans (DFSP) is typically diagnosed during early adult life at a tumoral stage. It occurs only rarely in children. We report six childhood cases of DFSP which presented initially with the misleading clinical appearance of atrophic plaques, and we review over 140 cases of DFSP in childhood. As compared with adult forms, DFSP in children does not show distinctive features except for a tendency for acral localization. The diagnosis is difficult because of the slow course of the lesions, which present initially as apparently benign atrophic morphoeaor keloid-like plaques. We believe that DFSP in childhood is probably under-estimated, as a significant proportion of patients diagnosed as young adults had an onset several years earlier. Better knowledge of the initial appearance is important for making an early diagnosis and for an easier surgical treatment.
The ability of blood coagulation factor XIII (FXIII) to affect collagen synthesis and degradation led to its use in the treatment of scleroderma. Encouraging initial results were achieved principally in terms of skin sclerosis, musculoskeletal involvement and weakness. Further assessment of this treatment in scleroderma was abandoned when, following the HIV epidemic, FXIII use became strictly regulated. Safer concentrates are now available which may allow us to reconsider this therapy. This paper, which briefly reviews available data related to FXIII use in scleroderma and which proposes general rules for prescribing, is aimed at generating an open debate as to the need to widen the regulated use of FXIII to scleroderma.
There is compelling animal and human experimental evidence that leukocytoclastic vasculitis is a hypersensitivity vasculitis, similar in nature to the experimental Arthus reaction. The immune complexes formed in antigen excess circulate until some event occurs that cause deposition in blood vessel walls. Adhesion molecules and cytokines released by endothelial cells and activated neutrophils represent a key factor in this process. The membrane attack complex of complement plays a significant role in altering the endothelial cell membrane integrity. Activated neutrophils release proteolytic enzymes, especially collagenases and elastases, along with free oxygen radicals that damage the vessel walls and the surrounding tissues. It remains uncertain whether antineutrophilic cytoplasmic antibodies, anti-endothelial antibodies and anti-cardiolipin antibodies are epiphenomena or are directly involved in the disease process. Apoptotic cell death mediated by the Fas/Bc12 system is a feature of leucocytoclastic vasculitis. In conclusion, the post-capillary venule is the active orchestrator of neutrophils in leukocytoclastic vasculitis which mediate a complex series of endothelial/leukocyte interactions.
INTRODUCTION: Epidermolysis bullosa acquisita is a bullous dermatosis. Its etiology remains unknown and the efficacy of its treatment is low. OBSERVATION: We report the first association between epidermolysis bullosa acquisita, chronic hepatitis C and cryoglobulinemia, healing with interferon alpha and ribavirine. DISCUSSION: We suggest a role for hepatitis C virus in the pathogenesis of epidermolysis bullosa acquisita. We suppose a synthesis of autoimmune antibodies in a dysimmune environment. Interferon alpha and ribavirine might be a new therapeutic avenue but further studies are necessary to confirm it.
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BACKGROUND: Papuloerythroderma of Ofuji is an uncommon condition characterized by diffuse pruriginous eruptions of infiltrating papulae. The large folds are not involved. The eruptions are associated with lymphopenia and eosinophilia. Very few cases have been reported in the literature and because of their heterogeneous nature, there is some debate as to whether this is a single clinical entity or a particular presentation of erythrodermia; Immunomodulation is recommended. CASE REPORT: A 73 year-old man of asian origin living in France presented chronic pruriginous erythrodermia with flat purplish-brown confluent papulae which did not involve the large folds. Eosophilia and lymphopenia were present. The biopsy specimen evidenced dermal infiltration with CD4+CD45+RO+ T cells, eosinophils and DC1a+ dendritic cells. Further explorations did not reveal any sign favoring lymphoma, carcinoma or underlying infection. Dermocorticoids, PUVA-therapy and interferon-alpha were ineffective. Considerable clinical improvement was obtained with cyclosporine A. DISCUSSION: We used ciclosporine A in our patient after repeated failure of other therapies reported to be effective in this dermatosis. Despite the favorable outcome, this therapeutic approach should be used with prudence.
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Vascular endothelial growth factor (VEGF), an endothelium-specific growth factor and microvessel hypermeability factor, is expressed and secreted by several kinds of cells and is implicated in angiogenesis of tumors. The present study was performed to determine the relationship between the expression of VEGF in normal skin, benign and malignant epithelial lesions and cultured keratinocytes and the proliferative activity and degree of differentiation of keratinocytes. Skin lesions were studied immunohistochemically by staining with two anti-VEGF antibodies and secretion and production of VEGF by keratinocyte cultures were evaluated using an enzyme-linked immunosorbent assay. Low to moderate VEGF expression was observed in normal epidermis. In epithelial tumors, different reactivity patterns were observed and different areas of the same tumor expressed different amounts of VEGF. A more prominent labelling occurred in proliferative layers and/or more differentiated cells of virus-induced lesions, squamous cell carcinomas and Bowen's disease, whereas basal cell carcinomas always stained weakly for VEGF. In cultured keratinocytes, the amount of cell-associated and secreted VEGF increased with time, and the constitutively produced VEGF was mostly released extracellularly. High calcium concentrations upregulated the intracellular content of VEGF but downregulated its release. Taken together, these results showed a modulated expression and release of VEGF in relation to the stage of cell differentiation and in rapidly growing or activated keratinocytes.
Substance P (SP) is distributed in both the central and peripheral nervous system. It has various effects on immunocompetent cells, such as macrophages and lymphocytes. The aim of our study was to search for the presence of SP receptors (SP-R) on human cutaneous Langerhans cells (LC), and to determine the effects of SP on LC immunological functions in a model of mixed epidermal cell-lymphocyte reaction (MELR). Radioligand binding studies showed that LC-enriched epidermal cell suspensions reversibly bound SP, and that the specific binding increased with the percentage of LC. Functional assays showed that SP had no effect when added at concentrations from 10(-6) M to 10(-12) M to the MELR. The addition of SP at concentrations of 10(-4) M and 10(-5) M was able to inhibit the allogeneic T-cell response (98.3 +/- 1.8% and 92.8 +/- 8.9% inhibition, respectively) without modifying the cell viability. This inhibition was through an effect of SP on both T-cell and LC function. We conclude that SP has receptors on LC and may inhibit antigen presentation.
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory dermatosis that probably involves a dysregulated activation of helper T cells, type 2 (Th2 cells). Severe refractory AD can be controlled by cyclosporine treatment. OBJECTIVE: We attempted to determine whether short-term CD4 monoclonal antibody (mAb) therapy could improve severe AD in adults. METHODS: The CD4 mAb, B-F5, was infused over 2 days in three patients with severe refractory AD and, for control purposes, in two patients with severe psoriasis. RESULTS: Administration of B-F5 was well tolerated, despite moderate first dose side effects. Clinical improvement was observed in two patients. In the third patient, a dramatic worsening occurred between 8 and 30 days after treatment, associated with an increased percentage of activated CD4+, CD25+, HLA-DR+, and CD45RO+ cells and peripheral blood eosinophilia. The same CD4 mAb administered to two patients with severe psoriasis induced marked clinical improvement of the lesions. CONCLUSION: Although CD4 mAb infusion may be potentially useful in the treatment of AD, the risk of aggravating the Th1/Th2 imbalance in AD should be considered in the design of future protocols.
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This study describes the presence in sera from patients with linear IgA bullous dermatosis (LABD) of IgA antibodies specific for 230- or 180-kDa epidermal antigens. Of 11 patients' sera with IgA antibodies reactive with the epidermal antigens obtained from cultured keratinocytes, 6 sera recognized the 230-kDa antigen and co-migrated with the polypeptide recognized by a human monoclonal antibody against the 230-kDa bullous pemphigoid antigen (BPAgl). Five sera recognized the 180-kDa antigen and co-migrated with the polypeptide stained by a polyclonal antibody to the 180-kDa bullous pemphigoid antigen (BPAg2). None of these LABD sera contained IgG antibodies reactive with the basement membrane zone antigens and none labeled a 97-kDa epidermal antigen or a 290-kDa dermal antigen. Immunoaffinity-purified IgA antibodies from the 230 kDa band further reacted with the epidermal side of the skin basement membrane zone. Epitope mapping with rBP55, a fusion protein containing the C-terminal end of BPAg1, suggested that the major antigenic epitopes for LABD and BP antibodies on the 230-kDa antigen are different. Only one serum with IgA antibodies was found to label rBP55, contrasting with nine of ten BP sera reacting with this protein. Our study demonstrates the presence of an exclusive IgA response against the 230- or 180-kDa antigens in a subset of patients with LABD.
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