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Immunoglobulin G (IgG) antibodies reactive with intracellular components of transformed cells were detected in 26/35 sera from patients with melanoma using immunofluorescence and/or Western blotting. By extracting cellular proteins with either sodium dodecyl sulphate or moderate concentrations of salt (400 mM NaCl), the protein antigens were partially characterized by immunoblotting procedures. Although considerable heterogeneity in the molecular weights of the protein antigens was observed, two common groups were delineated. The anti-Pol antibodies reacted with 30 kd cytoplasmic protein and the anti-Ca antibodies recognized acidic high molecular weight (75 - 95 kd) proteins. These antigens were detected in all transformed cell lines tested, but were not restricted to them. Anti-Ca and anti-Pol antibodies were not found in sera from patients with other solid tumors or in systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

The immunologic specificity of bullous pemphigoid (BP) antigens expressed in human skin was studied by reacting the sera of 34 patients with BP with several specimens of normal skin. Most sera with basement membrane zone (BMZ) antibodies reacted to antigens expressed in all specimens of skin examined. A minority of pemphigoid sera reacted to BP antigens expressed in some specimens of skin but not in others. The pattern of cross-reactivity suggests that BP antigens are heterogeneous and that two different groups can be defined serologically. The first is a universal BP antigen(s) which is expressed in all individuals and to which antibodies are formed in most patients with BP. The other group consists of a family of BP antigens whose expression varies from individual to individual. Several immunologically distinct BP antigens can be expressed concurrently in the same specimen of skin. Lastly, the apparent absence of BMZ antibodies in some patients with BP is occasionally the result of antibodies directed to "minor" BP antigens with restricted expression. [ABSTRACT FROM AUTHOR]

Direct immunofluorescence studies were performed on hairy and alopecic areas of scalp in patients with alopecia areata, alopecia totalis and male pattern alopecia. Abnormal deposits of C3 and occasionally of IgG and IgM were found in 92% of 12 patients with alopecia areata and in 21% of patients with male pattern alopecia. No abnormalities were seen in 4 patients with alopecia totalis. In both alopecia areata and male pattern alopecia, the deposits were most common along the basement zone of the inferior segment of hair follicles and occurred with equal frequency in alopecic and normal scalp. These observations suggest that immune factors may play a role in the pathogenesis of alopecia areata. [ABSTRACT FROM AUTHOR]

Cytoplasmic antigens of 3 different specificities are expressed concurrently in the epidermis of normal human skin. They differ by their location in distinct layers of the epidermis. One type is present in all epidermal cells, another only in cells of the superficial layers, and the third only in basal cells. All 3 antigens were present in 10 specimens of normal human skin. The superficial and basal cell antigens were absent in 4 basal cell epitheliomas and 3 squamous cell carcinomas. This finding, together with the stratification of the antigens in different layers of the skin, suggests epidermal cytoplasmic antigens are differentiation antigens. [ABSTRACT FROM AUTHOR]

The reproducibility of the indirect immunofluorescent test for antibodies to human malignant melanoma cytoplasmic antigens was investigated by testing panels of melanoma and normal sera against cells of each of several different melanomas. Tests were performed in replicate, read blindly by two observers, and repeated on different days. Different observers agreed in the interpretation of replicate assays in approximately 80 to 90% of cases. Variability increased considerably when assays were repeated on different days or when different melanomas were used as substrate. Under these circumstances, similar results were obtained in as few as 21% of test. Thus, the results of the indirect immunofluorescent test for melanoma cytoplasmic antibodies must, at the present time be interpreted with great caution. [ABSTRACT FROM AUTHOR]

Antibodies to epidermal cytoplasmic antigens were present in 25 to 34% of 32 normal persons and in 34 to 50% of 53 patients with melanoma. There were at least two different types of cytoplasmic antibodies. The most common reacted to cytoplasmic antigens present only in the upper layers of the epidermis. This type of antibody occurred with equal frequency in patients with melanoma and in normal persons. The increased incidence of cytoplasmic antibodies in melanoma was due to antibodies to cytoplasmic antigens present throughout the epidermis. These antibodies were 2½ times more common in patients with melanoma than in normal persons. The presence of different cytoplasmic antigens in distinct strata of the epidermis suggests they result from epidermal cell differentiation. The epidermal cytoplasmic antigens present throughout the epidermis appear to partially cross-react with cytoplasmic antigens in melanoma cells. [ABSTRACT FROM AUTHOR]

The growth of fresh and I issue cultured B-16 malignant melanoma cells in C57BL/6 mice was quantitated, using as parameters the latent time to tumor appearance, tumor incidence, and mortality rate. The tumor was antigenic, as evidenced by the appearance of humoral antibodies to melanoma-associated antigens during the natural growth of this tumor and by the induction of resistance to lethal doses of tumor by immunization with repeated injections of irradiated, or sublethal doses of viable, melanoma cells. This immunity was not entirely specific, since mice immunized to B-16 melanoma were slightly resistant to challenge with BW10232 mammary adenocarcinoma and, conversely, mice immunized to mammary adenocarcinoma were slightly resistant to melanoma. [ABSTRACT FROM AUTHOR]

The diagnosis of autoimmune blistering skin disease is increasingly based on the skin antigen(s) that is the target of the autoimmune process. Some patients with bullous diseases have unusual basement membrane autoantibodies that react to antigens present in both the epidermal and dermal sides of skin split with 1 M NaC1. This combined staining pattern is due to antibodies directed in part to a 160-kilodalton (kD) basement membrane antigen present on the epidermal side of the split skin and to different antigen(s) present on the dermal side. The identity of the current antigen(s), and the significance of this unusual type of combined staining antibody response is not known. Sera of five patients with combined staining antibodies, 19 patients with other types of basement membrane antibodies (15 directed only to the epidermal and four only to the dermal side of split skin), and 23 patients without basement membrane antibodies were tested by Western immunoblot for reactivity to 4% sodium dodecyl sulfate + 2 M urea extracts of dermal and epidermal side of salt-split skin. Three (60%) of the combined staining sera had antibodies to an 82- 84-kD antigen (p84) reproducibly present in dermal, but not epidermal, extracts of normal human skin. Antibodies to this antigen were absent in the 42 control sera. Western blot affinity-purified antibody to p84 bound only to the basement membrane, on the dermal side of 1 molar salt-split skin. By co-migration experiments, p84 differed from other basement membrane antigens including the major and minor bullous pemphigoid, cicatrizing pemphigoid, and epidermolysis bullosa acquisita antigens, types III and IV collagen, laminin, and epiligrin. Thus, combined staining antibodies are directed in part to an 82-84-kD antigen (p84), a normal but previously undescribed component of the basement membrane of human skin. This antigen differs from the basement membrane antigens recognized by autoantibodies in other subepidermal bullous diseases. The antibody response to p84 provides a specific marker for a novel autoimmune subepidermal blistering skin disease. [ABSTRACT FROM AUTHOR]

The expression of U-CYT antigens, tissue-specific cytoplasmic antigens of keratinocytes that are markers of the terminal differentiation of these cells, was studied in normal skin adjacent to malignant epidermal tumors. Ten basal-cell carcinomas were studied. In all cases, it was found that the expression of U-CYT antigens in normal epidermis gradually decreased with increasing proximity to the tumors and finally disappeared completely within the tumor tissue itself. This finding suggests that basal-cell carcinoma can alter the normal differentiation of adjacent nonmalignant cells. [ABSTRACT FROM AUTHOR]

There is considerable indirect and some direct evidence that immune mechanisms can play an important role in controlling the growth of melanoma. In mice, melanoma can be prevented with vaccines. Consequently, even though naturally occurring immunosurveillance may not be sufficiently potent to prevent melanoma, it is possible that the prophylactic augmentation of immunity to melanoma with vaccines may eventually permit this cancer to be prevented in humans. [ABSTRACT FROM AUTHOR]

Presents a response by the author to a letter to the editor about epidermal cytoplasmic antigens.

Macromolecules expressed on the external surface of human keratinocytes in tissue culture were radioiodinated by the lactoperoxidase technique and solubilized by lysing the cells in nonionic detergent. Soluble labeled proteins were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The pattern of proteins expressed by keratinocytes was distinct for these cells. The major labeled components had Mrs of 28K, 40K, 68K, 72K, and 77K. The expression of several macromolecules changed with the length of time the cells were in culture, suggesting that their expression was linked to epidermal differentiation. Lastly, many but not all of the macromolecules expressed on the surface of keratinocytes were selectively and rapidly released into medium by the cell. [ABSTRACT FROM AUTHOR]

Patients with vitiligo have been found to have circulating antibodies to pigment cells. To evaluate the functional activity of these antibodies, a highly sensitive europium release assay was used to compare complement-mediated cytolysis of human melanocytes by sera of 56 patients with vitiligo (20 with active disease, 25 with inactive disease, 11 with unidentified disease activity) and 47 control individuals. Significant melanocyte lysis was mediated by 32 (57%) of the patients with vitiligo but by only three (6%) of the control sera (p < 0.00 1), and by 17 (85%) of 20 patients with active vitiligo versus 11(44%) of 25 patients with inactive disease (p < 0.025). Mean melanocyte lysis by vitiligo sera was 24% versus 6% by control sera (p <0.0001). A subset of 12 vitiligo sera with high titers of cytolytic antibodies to melanocytes (34% mean cytolysis) reacted minimally (<2% mean cytolysis) to a panel of control cells that included human and murine melanomas, human fibroblasts, lung carcinoma, and rhabdomyosarcoma. These findings indicate that antibodies present in patients with vitiligo have the functional ability to selectively kill melanocytes and are more common in active disease. These observations support, but do not prove, the hypothesis that vitiligo is an autoimmune disease and that antipigment cell antibodies have a role in inducing the disease. [ABSTRACT FROM AUTHOR]

Our laboratory has recently reported that over 80% of patients with common vitiligo have circulating antibodies to cell-surfacer antigens on normal human melanocytes. The slow growth rate of these cells limits the assays that can be performed for antibody detection. We now have found that the antigens defined by vitiligo sera on melanocytes are also expressed on FF cells, a revertant line of hamster melanoma cells. These antigens can be detected both by indirect immunofluorescence and specific immunoprecipitation assays. The presence of "vitiligo" antigens on hamster FF cells will aid further study of the abnormal immune response in vitiligo. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which responds to the study by I.J. Vergilis and colleagues entitled "Presence and prognostic significance of melanoma-associated antigens CYT-MAA and MNW-MAA in serum of patients with melanoma," previously published in the "Journal of Investigative Dermatology".

Patients with vitiligo have circulating antibodies to pigment cells. To characterize this response further and to identify the antigens defined by vitiligo antibodies, sera of 23 patients with vitiligo and 22 patients with unrelated conditions were analyzed by immunoprecipitation and SDS-PAGE analysis of 125I-labeled cell antigens on pigment and control cells. Antibodies to pigment cell antigens were present in 18 (78%) of the patients with vitiligo but in only three (14%) of the control patients (p < 0.05). The antibodies were directed to one or more antigens with molecular weight (MW) in kilo-daltons (kD) of approximately 35, 40-45, 75, 90, or 150. The responses were most commonly directed to the 40-45-kD, 75-kD, and 90-kD antigens. Antibodies to these antigens were present in 74%, 57%, and 35% of vitiligo patients versus in 14%, 9%, and 0% of control individuals. The 35-kD and 90-kD antigens were preferentially expressed on human pigment cells, whereas the 40-45-, 75-, and 150-kD antigens were expressed on both pigment and control cells. These antigens were labeled by the lactoperoxidase technique, suggesting that they are cell surface antigens. These results confirm that antibodies to pigment cells are associated with vitiligo. These antibodies are directed to several cell surface antigens, some of which are preferentially expressed on pigment cells. [ABSTRACT FROM AUTHOR]