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The epidermolysis bullosa acquisita antigen is a major constituent of the basement membrane zone beneath stratified squamous epithelium. The antigen which is recognized in extracts of skin basement membrane by Western blot analysis with polyclonal or monoclonal antiepidermolysis bullosa acquisita antigen antibodies as 2 chains (a major chain of 290,000 and a minor chain of 145,000) has a native molecular weight over 800,000. Both epidermolysis bullosa acquisita antigen chains contain carbohydrate and the 290K chain is sensitive to collagenase.

Despite recent advancements in therapy, melanoma remains a highly lethal skin cancer. A better understanding of the genetic and epigenetic changes responsible for melanoma formation and progression could result in the development of more effective treatments. Advanced melanomas are known to exhibit widespread promoter region CpG island methylation leading to the inactivation of key tumor suppressor genes. Meta-analyses of relevant microarray data sets revealed the hematopoietic stem cell regulator gene latexin (LXN) to be commonly downregulated in approximately 50% of melanomas. The CpG island in the promoter region of LXN was almost universally hypermethylated in melanoma cell lines and tumors, and treatment of the cell lines with the demethylating drug 5-aza-2'-deoxycytidine resulted in increased LXN expression. In this paper, we demonstrate that the exogenous expression of LXN in melanoma cell lines results in a significant inhibition of tumor cell proliferation. In addition, we show that the increased expression of LXN in these lines correlates with reduction in the expression levels of stem cell transcription factors OCT4, NANOG, SOX2, KLF4, and MYCN, indicating that LXN may exert its tumor-suppressive function by altering the stem cell-like properties of melanoma cells.

Recent papers have reported that there are at least two distinct binding sites of bullous pemphigoid (BP) antibodies; one is the extracellular (lamina lucida) BP antigen (E-BPA) and the other is the intracellular (basal cell cytomembrane-hemidesmosome-cytoskeleton) BP antigen (I-BPA). In attempting to characterize the properties of these two BP antigens (BPA), we have investigated the expression of E-BPA and I-BPA as well as other basement membrane zone (BMZ) components such as type IV collagen, laminin, and epidermolysis bullosa acquisita (EBA) antigen at the dermal-epibolic junction as a model system for BMZ neogenesis. I-BPA was found along the dermal-epidermal junction and throughout the whole length of the dermal-epibolic junction. However, E-BPA and other BMZ components were found along the dermal-epidermal junction and along only the most proximal portion of the dermal-epibolic junction. These results suggest 1) that emergence of E-BPA varies from that of I-BPA in such a model system of BMZ neogenesis, and 2) that the emerged E-BPA may attach to the newly formed basement membrane complex.

Pemphigus foliaceus (PF) and its endemic form, Fogo Selvagem (FS), are characterized by subcorneal vesicles and pathogenic IgG autoantibodies directed against keratinocyte surface antigens. A major pool of FS antigen(s) remains bound to the insoluble epidermal envelope fraction. In this paper we demonstrate that this antigen(s) can be released From the envelope fraction by sonication. By immune precipitation four components can be detected, having molecular weights (MW) of 260, 80, 62, and 45 kD. The 260-kD component is lost by boiling or extraction with glycine HG! at pH 2.8. The major components appear to be the 80- and 62-kD poly-peptides. They chromatograph as a unit by gel filtration in 0.1% SDS, in the MW range of 115-120 kD. The FS antigen(s) appears to be cationic, forming insoluble complexes at low pH with SDS, and is labile to ammonium sulfate and freezing and thawing. It is unaffected by positive pressure concentration, 50% acetone precipitation, and reduction/alkylation. The FS antigen(s) is precipitated by all FS and nonendemic PE sera except those in complete clinical and serologic remission. The FS antigen(s) is also precipitated by 50% of pemphigus vulgaris but none of the bullous pemphigoid sera tested. All FS antigenic components are immunoprecipitated by IgG4 autoantibodies, but the IgG1 subclass from the same patients appear to immunoprecipitate only the 62-kD polypeptide. The ES antigen(s) is able to adsorb human autoantibodies against human desmoglein 1 (DG1), but not rabbit antisera against bovine DG1 or 2. This paper shows that physical stress, i.e., sonication, may be able to solubilize sufficient ES antigen(s) from the epidermal envelope fractions for further chemical characterization. The relationship of these PS antigen(s) to other reported FS antigens is presently unknown. [ABSTRACT FROM AUTHOR]

This article presents the research papers presented in the Thirteenth Annual ADF Meeting, which was held in November 1985 at Vienna, Austria. The paper on "Tac Antigen Expression by Malignant Lymphocytes Infiltrating the Skin-Pathogenetic Considerations," by V. Groh, U. Kö ller and G. Stingi focuses on T cell proliferation. Some other topics covered are cutaneous lesions in histiocytosis X, HTLV-1 positive primary cutaneous B-cell Lymphoma, and human epidermal, Langerhans cells in culture.

This paper describes a sensitive and specific immunoblotting procedure to detect Ro(SS-A) and La(SS-B) autoantibodies in the serum of patients with lupus erythematosus. In order to perform this procedure, we have partially purified the Ro(SS-A) and La(SS-B) antigens from human spleen extracts by DEAE-cellulose and Sephacryl S-300 chromatography. The Ro(SS-A) and La(SS-B) antigens were immobilized on nitrocellulose paper after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tested against a panel of sera at different dilutions: normal bureau sera (n = 14), Ro(SS-A) antisera (n = 6), La(SS-B) (n = 7), Ro(SS-A)/La(SS-B) (n = 8), Sm-nRNP-La(SS-B) (n = 2). We found that Ro(SS-A) antisera react with a protein of an approximate Mr of 58K, whereas the La(SS-B) antisera reacted with two bands of Mr 42 and 40K, respectively. Antisera with both autoantibodies [Ro(SS-A) and La(SS-B)] reacted with both antigens, whereas the control NHS, anti-nRNP, and anti-Sm did not stain the Ro(SS-A) and La(SS-B) protein bands. In addition, some of the positive sera continued reacting with the respective antigens at extremely high dilutions. This procedure can be easily adapted to test many serum samples and produce data which include Mr of the antigen and titer of autoantibodies in the patient's serum. [ABSTRACT FROM AUTHOR]

Ψ-3 is a monoclonal antibody that recognizes a 135,000 molecular weight structural component of maturing keratinocytes in psoriasis (the Ψ-3 antigen) but fails to bind to any constituent of keratinocytes in normal epidermis. This paper describes the occurrence of the Ψ-3 antigen in a variety of dermatopathologic conditions using immunoperoxidase (biotin-avidin-peroxidase) and immunofluorescence methods which show excellent concordance. In 35 of 36 specimens of psoriasis vulgaris, Ψ-3 antibody consistently immunolabels the cytoplasm of keratinocytes above the basal layer. At the edges of psoriatic plaques, Ψ-3 antibody staining extends for a variable distance into lesion-free epidermis. A similar pattern has been found in a certain number of other conditions described in the paper, including squamous cell carcinoma and condyloma acuminatum, but not Darier's disease basal cell carcinoma, nor lamellar ichthyosis. In all but one condition, the outermost or basal layer of cells is never stained. The only disease in which the lowermost cell layer is stained is a lichen planus-like lesion. The occurrence of Ψ-3 antigen cannot be correlated with any histologic feature of psoriasis such as acanthosis, loss of the granular layer, or hyperproliferation. The antigen appears to be a unique keratinocyte constituent which is expressed in certain pathologic conditions and which is not detected by any other histologic or immunophenotyping method. It is a potentially valuable addition to the panel of antibodies available for characterizing epithelial cells. [ABSTRACT FROM AUTHOR]

The article informs about the details of the Thirty-first Annual Meeting of the Society for Investigative Dermatology, Inc, to be held On June 20 and 21, 1970, at the Sheraton Chicago Hotel, Chicago, Illinois. Many papers will be presented at this meeting. The paper titled "Ultrastructural Autoradiographic Study of Molluscum Contagiosum Virus Maturation In Vivo," informs that tritiated thymidine when injected into lesions of molluscum contagiosum incorporates into DNA of germinative cell nuclei, as well as into cytoplasmic inclusions of infected spinous and granular cells. The paper titled "Antigens of Human Wart Tissue," informs about experimental animal tumors caused by papova viruses contain cellular antigens which relate to tumor rejection.

This paper presents a study of autoantibodies (autoAB) to keratins and to epidermis by a double approach associating a specific immunoenzymatic technique and immunofluorescence. The existence of natural autoAB to keratins in all normal human sera was asserted and the heterogeneity of natural autoAB to the epidermis explored. By a sensitive enzyme-linked immunosorbent assay we detected natural IgM and IgG auto AB to keratin polypeptides extracted from human plantar stratum corneum (SC) in 60 randomly selected normal human sera. The interindividual variation factors of their titers were about 100 ×in IgM and 50 × in IgG antikeratin (AK) autoAB. The IgM and IgG AK autoAB titers varied independently. By a semiquantitative indirect immunofluorescence assay we detected in these sera IgM and IgG autoAB that labeled normal epidermis according to various morphologic patterns. The IgG autoAB labeled SC and suprabasal layers (SBL) in 57.4% of sera, SC in 20.4% and SBL in 7.4%. The IgM autoAB labeled SC and SBL in 52% of sera, SC in 24%, SC and SBL plus basal layer (BL) in 18%, and SBL in 2%. Like the titers, the patterns of IgM and IgG autoAB to epidermis were found to be unrelated. The IgG AK autoAB titers were found to significantly correlate only with the IgG autoAB directed to SC + SBL; the IgM AK autoAB titers only with the IgM autoAB directed to SC + SBL + BL. This showed that these patterns of labeling are typical for AK autoAB and that autoAB to SC, which could not be related to AK autoAb, exist in some normal sera. Antikeratin and antiepidermis IgM autoAB titers were found to be strongly correlated to total amounts of IgM assayed by radial immunodiffusion, indicating that the synthesis of these natural IgM autoAB vary in the same way as that of general IgM autoAB vary in the same way as that of general IgM synthesis. For the AK and antiepidermis IgG autoAB, however, the same correlation to total serum IgG was found to be much weaker. [ABSTRACT FROM AUTHOR]

Photosensitivity associated with lupus erythematosus (LE) is well established. The photobiologic basis for this abnormal response to ultraviolet radiation, however, has not been determined. This paper summarizes the criteria for elucidating possible photobiologic mechanisms and reviews the literature relevant to the mechanism of photosensitivity in LE. In patients with LE, photosensitivity to wavelengths shorter than 320 nm has been demonstrated; wavelengths longer than 320 nm have not been adequately evaluated. DNA is a possible chromophore for photosensitivity below 320 nm. UV irradiation of skin produces thymine photodimers in DNA. UV-irradiated DNA is more antigenic than native DNA and the antigenicity of UV-irradiated DNA has been proposed, but not proven, to be involved in the development of clinical lesions. UV irradiation of mice previously injected with anti-UV-DNA antibodies produces Ig deposition and complement fixation that appears to be similar to the changes seen in lupus lesions. Antibodies to UV-irradiated DNA occur in the serum of LE patients although a correlation between antibody titers and photosensitivity was not observed. Defective repair of UV-induced DNA damage does not appear to be a mechanism for the photosensitivity in LE. Other mechanisms must also be considered. The chromophore for photosensitivity induced by wavelengths longer than 320 nm has not been investigated in vivo. In vitro studies indicate that 360-400 nm radiation activates a photosensitizing compound in the lymphocytes and serum of LE patients and causes chromosomal aberrations and cell death. The mechanism appears to involve superoxide anion. Further research is required to establish the action spectrum for long wavelength photosensitivity in vivo and to elucidate the mechanisms for the photosensitivity at all wavelengths. [ABSTRACT FROM AUTHOR]

The article introduces research papers included in the September 1992 issue of "Journal of Investigative Dermatology." In this issue of the journal main focus has been drawn towards the study of bullous pemphigoid (BP) which is an autoimmune disorder associated with subepidermal blistering and disruption of interactions between basal keratinocytes and the cutaneous basement membrane. Sera from affected individuals contain antibodies that recognize two distinct antigenic elements of the hemidesmosome. In this issue three papers fully analyze the composition of the BP180 antigen.

Epidermal Langerhans cells are dendritic bone marrow-derived cells which synthesize and express Ia antigens. During the past decade, in vitro studies have demonstrated that they play a critical role in the induction of many types of T-cell responses. Specifically, Langerhans cells are effective antigen-presenting cells in allogeneic and antigen specific proliferative and cytotoxic T-cell responses. This paper reviews these functions and suggests areas of future investigations into the mechanisms involved in T-cell activation by Langerhans cells. [ABSTRACT FROM AUTHOR]

This is the third and final portion of a report of a project designed for the purpose of improving standard methods of detecting contact allergens. The first dealt with the theoretical and technical insufficiencies of the conventional "predictive" tests. The second presented a compendium of experimental information on the various agencies which conduce to the establishment and measurement of human contact sensitization. It is the purpose of this paper to present a new method of bioassay, hereafter called the "Maximization Test," and to record the performance of this test with a score of well known substances. The objective of the maximization test is to establish whether specified substances have allergenic potentialities and to what degree. The test is primarily designed to yield allergenicity ratings for individual substances, not complex mixtures, finished products or formulations, it must be thoroughly understood that the maximization procedure does not directly assess safety in use .