Pemphigus antibody action on skin explants: kinetics of acantholytic changes and stability of antigens in tissue cultures of normal monkey skin explants

Deng, Jau‐Shyong

doi:10.1001/archderm.113.7.923

Cited by 33 publications

(6 citation statements)

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“…Skin cultured with normal human serum did not undergo acantholytic changes. Similar results were seen using organ cultures of monkey skin [5,16]. Ultrastructural analysis of organ cultures grown in the presence of pemphigus serum demonstrated changes similar to those observed in the skin of pemphigus patients [29].…”

Section: Experimental Studies On the Mechanism Of Acantholysis In Pemsupporting

confidence: 70%

Antibody-induced proteinase activation: A proposed mechanism for pemphigus

Singer

Hashimoto

Lazarus

1981

Springer Semin Immunopathol

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The current state of understanding of pemphigus includes the following: 1. Pemphigus is an autoimmune disease. In all variants a circulating autoantibody is found which binds to epidermal cells. In vivo antibody may be found deposited in the epidermis of patients. 2. The autoantibody levels generally correlate with disease activity indicating a relationship between antibody and clinical disease. 3. Although complement components are found in lesional skin, complement does not appear to be necessary for dissolution of the epidermal cement substance. 4. The treatment of pemphigus with corticosteroids has drastically reduced mortality rates. 5. Three different groups have presented results in two different experimental systems which indicate that subsequent to binding of pemphigus antibody to epidermal cells a proteinase is activated. This proteinase(s) degrades the intercellular cement substance of epidermis which results in loss of cellular adhesion and acantholysis. There are numerous questions still remaining. What is the nature of the proteinase(s) and the surface protein(s) it cleaves? Does the binding of pemphigus antibody to the cell surface induce enzyme synthesis, specific enzyme activation, or generalized lysosomal secretion? The answers to these questions will have broad biologic relevance since they may elucidate the role of anticell surface antibodies in disease states.

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Section: Experimental Studies On the Mechanism Of Acantholysis In Pemsupporting

confidence: 70%

Antibody-induced proteinase activation: A proposed mechanism for pemphigus

Singer

Hashimoto

Lazarus

1981

Springer Semin Immunopathol

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“…Definitive evidence that serum from pemphigus patients can produce the characteristic histological lesion of pemphigus has been established in organ culture studies with human (4)(5)(6)(7)(8) or monkey (9) skin. The antibody binds to the epidermal cells before the onset of acantholysis.…”

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confidence: 99%

Pemphigus antibody interaction with human epidermal cells in culture.

Schiltz¹,

Michel²,

Papay³

1978

J. Clin. Invest.

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A B S T R A C T The mechanism of pemphigus acantholysis has been studied with an in vitro system. Freshly prepared human skin epidermal cells were incubated in F-10 medium which contained the immunoglobulin G fraction from either pemphigus serum or normal human serum. During 18-h incubation periods, the pemphigus antibody became bound to the surface ofthe epidermal cells, caused the destruction of 75% of the viable cells as compared to only 14% in the normal immunoglobulin G controls (trypan blue exclusion), prevented the accumulation of newly synthesized proteins by nearly 60% as determined by radioactive tracer studies, and caused a dramatic shift in distribution of the newly synthesized proteins from an insoluble cell-associated fraction to an extracellular soluble fraction. These effects on the accumulation and partitioning of newly synthesized proteins were antibody concentration-dependent. Kinetic studies showed that at a fixed pemphigus antibody concentration the inhibition of protein accumulation preceded solubilization by about 1 h, at which time rapid solubilization of up to 70% of the insoluble cellular material occurred. Several lines of evidence suggested that this phenomenon was caused by enzymatic activity. Epidermal extracts solubilized a prepared substrate of radioactively labeled insoluble epidermal cell material. This activity was heat labile and pH dependent, with pH optima ranging from 4.5 to 6.5. Enzymes with pH optima between 6 and 6.5 were recovered in the culture medium after a 2-day incubation of pure, intact epidermis with the pemphigus antibody.We propose the following hypothesis to account for pemphigus acantholysis. The pemphigus antibody reacts with the epidermal cell surface and produces such a severe disturbance that the integrity of the cell

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“…Another important difference between in vitro and in vivo phenomena is that the acantholysis in culture is not accompanied by formation of bullae in the skin of patients at the site from which culture material was obtained. The studies of Deng et al (1977) on the disappearance of the pemphigus antigen in tissue culture (i.e., differentiation) suggests one possible mechanism, i.e., the failure of bullae to develop in vivo adjacent to the sites of biopsy may be due to the fact the pemphigus antigen is synthesized in vivo more rapidly than the bound pemphigus antibodies can induce acantholytic change, while little or no such synthesis of antigen occurs in vitro. This problem obviously merits further study.…”

Section: Discussionmentioning

confidence: 99%

“…Skin cultures were performed as described previously (Binder et al 1978, Deng et al 1977. Biopsy specimens were taken under topical anesthesia (Xylocain Spray) with a scalpel.…”

Section: Methodsmentioning

confidence: 99%

“…The pathogenicity of pemphigus antibodies has now also been demonstrated with skin explants maintained in tissue culture with pemphigus antibodies (Binder et al 1978, Deng et al 1977, Michel & Ko 1977, Schlitz & Michel 1976. That is, normal skin incubated in the presence of serum containing pemphigus antibodies or isolated IgG fractions bind the pemphigus antibodies to the intracellular areas of the epidermis after 12 to 18 h, and after 24 to 48 h acantholytic fissures form.…”

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confidence: 96%

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Immunopathologic and Histologic Studies on Skin from Pemphigus Patients in Tissue Culture

1979

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Explants of skin from patients with pemphigus vulgaris and pemphigus foliaceus taken in the active stages of the disease had in vivo bound IgG in the intercellular area. After 24-48 h incubation of these explants in normal sera acantholytic bullae developed above the stratum basale, thus indicating that the bound IgG is probably in vivo bound pemphigus antibody. In both cases, skin from the inactive stage of the disease contained no in vivo bound pemphigus antibodies. Explants of these skin specimens failed to develop acantholysis in culture.

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Pemphigus antibody action on skin explants: kinetics of acantholytic changes and stability of antigens in tissue cultures of normal monkey skin explants

Cited by 33 publications

References 5 publications

Antibody-induced proteinase activation: A proposed mechanism for pemphigus

Antibody-induced proteinase activation: A proposed mechanism for pemphigus

Pemphigus antibody interaction with human epidermal cells in culture.

Immunopathologic and Histologic Studies on Skin from Pemphigus Patients in Tissue Culture

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