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Biomedical subjects

R E Jordon

Publications and source records attributed to R E Jordon.

At least 19 recordsLinked to original sources
PubMed1995

Neonatal pemphigus foliaceus.

BACKGROUND: Pemphigus refers to a group of autoimmune blistering diseases of the skin. Of the two major types of pemphigus, pemphigus vulgaris and pemphigus foliaceus, only pemphigus vulgaris has been known to affect newborn infants via passive transfer of maternal IgG antibodies across the placenta. Although pemphigus foliaceus antibodies have also been shown to cross the placenta, never before has a newborn been clinically affected. We report the first of neonatal pemphigus foliaceus confirmed by both clinical presentation and immunofluorescence studies. OBSERVATIONS: The distinguishing factors in this case were high antibody titers by indirect immunofluorescence present in both the mother and her fetus (1:640 and 1:80, respectively). CONCLUSIONS: A threshold of fetal antibody titer ( > 1:40) may need to be surpassed before neonatal disease can occur in pemphigus foliaceus. The likelihood of reaching this threshold has been shown to be increased with higher maternal antibody titers. Thus, strict control of maternal pemphigus foliaceus should lower the incidence of placental antibody transfer and improve neonatal outcome.

Fluorescent Antibody Technique, Direct↗
PubMed1992

Bullous pemphigoid autoantibodies reactive with intracellular basal keratinocyte antigens: studies of subclass distribution and complement activation.

Using immunofluorescence (IF) and monoclonal antibodies (MoAbs) to IgG subclasses, terminal complement components, and S-protein/vitronectin, we have extended recent observations concerning reactivity of bullous pemphigoid autoantibodies with intracellular antigens located on the polar tips of basal human keratinocytes (HuK). Using three purified bullous pemphigoid IgG fractions, autoantibody reactivity with these intracellular antigens was present in all four IgG subclasses. When skin sections were used as substrate, an identical IgG subclass distribution of autoantibodies for each bullous pemphigoid IgG fraction was observed, but reactive with the basement membrane zone. All three bullous pemphigoid IgG preparations contained IgG subclass autoantibodies capable of complement fixation. Each IgG fraction resulted in fixation of all of the terminal complement components (C5, C6, C7, C8, and C9) and assembly of the membrane attack complex (MAC) on the polar tips of basal HuK. S-protein/vitronectin was not bound in a similar fashion. Normal IgG fractions yielded consistently negative reactions. Thus, bullous pemphigoid autoantibodies, fixed to polar tips of basal HuK, are found in all four IgG subclasses and will activate complement resulting in generation of MAC.

Antibodies, Monoclonal↗
PubMed1992

The surgical applications and implications of cultured human epidermis: a comprehensive review.

Replacement of skin has long been the ultimate task for surgeons facing skin-resurfacing challenges such as thermal burns and chronic ulcerations. Autologous skin grafts have been the "gold standard" for wound closure, but in patients who are massively burned, the availability of normal skin is the limiting factor. In the past 15 years the technique of in vitro cultivation of human epidermis has been developed in an attempt to deal with the problem of extensive skin loss. Although the technique is costly and arduous, grafting patients who are severely burned with cultured epidermal autografts has proved to be a life-saving measure where few alternatives exist. Cultured allografts have promoted rapid healing and pain relief in patients with chronic ulcers. Although longer follow-up is necessary, recent evidence suggests that cultured epidermis provides a wound cover that is just as durable and esthetically acceptable as conventional split-thickness skin grafts. This article reviews the development and applications of epidermal cell culture.

Animals↗
PubMed1990

Pemphigus immunoglobulin G subclass autoantibodies: studies of reactivity with cultured human keratinocytes.

The subclass distribution of pemphigus vulgaris (PV) autoantibodies has been investigated further. Cultured human keratinocytes (HuKs) were incubated with immunoglobulin G (IgG) fractions prepared from the serum samples of five patients with PV and one patient with pemphigus foliaceus (PF). The binding of IgG subclasses to HuK was detected by the use of indirect immunofluorescence done with monoclonal antibodies that were specific for each of the four human IgG subclasses. IgG1 and IgG4 binding to keratinocytes was detected in all of the pemphigus IgG preparations. In each instance, the titer of bound IgG1 was equal to or greater than the IgG4 titer. IgG3 binding was detected in only one PV IgG, and IgG2 pemphigus antibody activity was not detected. Differences in the immunofluorescence patterns between the five PV and one PF IgG and between the five PV and a second PF serum were noted. PV antigens were detected as a speckled pattern on HuKs, with accentuation in the intercellular spaces. By comparison, the pattern of PF antigen expression varied significantly depending on whether anti-IgG1 or anti-IgG4 antisera were used. Anti-IgG1 bound in a coarse granular pattern without accentuation in the intercellular spaces, but anti-IgG4 bound in a pattern nearly identical to that observed with PV IgG and its subclasses.

Antibodies, Monoclonal↗
PubMed1989

Chronic cutaneous lupus erythematosus.

Chronic cutaneous LE is a diverse disease, characterized by predominantly cutaneous disease with few systemic complications. Discoid lesions are commonly seen, but they are not specific for chronic cutaneous LE. These scarring and disfiguring changes are also present in neonatal LE, SLE, and complement deficiency LE. Because definitive diagnosis cannot be made by cutaneous examination alone, all patients should initially be evaluated for systemic disease. A small percentage of patients with chronic cutaneous LE will ultimately develop SLE, and therefore, patients should be re-evaluated periodically. The pathogenesis of the cutaneous lesions is not definitively known. There is suggestive evidence implicating T-cell mediated injury, especially in discoid LE. Antibody-dependent cellular cytotoxicity may also play a significant role in cellular damage in subacute cutaneous LE and neonatal LE, especially in the presence of anti-Ro antibody. Immunoglobulin deposition in association with membrane attack complex, has been associated with epidermal injury in some cases. Treatment of chronic cutaneous LE is largely symptomatic and nonspecific, focusing on reduction of inflammation. Further knowledge of pathogenesis will, hopefully, provide for specific immunologic therapy.

Humans↗
PubMed1989

Deposition of the membrane attack complex of complement in pemphigus vulgaris and pemphigus foliaceus skin.

The present study was performed to determine whether complement activation in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) results in the assembly of the terminal complement sequence or membrane attack complex (MAC) in skin lesions. Biopsy specimens of skin lesions from five patients with PV and three patients with PF contained C5, C7, C9, and the MAC related neoantigen (C5b-9 neoantigen) in intercellular substance areas (ICS), as well as IgG and the early complement components Clq, C4, and C3. The presence of these late complement components and the C5b-9 neoantigens in ICS sites of the skin lesions is indicative of complement activation by the pemphigus antibody, with subsequent assembly of the MAC. The binding of IgG and early complement components to ICS was observed in both non-lesional (normal appearing) skin and in skin lesions. However, no MAC could be detected in the normal appearing skin of our pemphigus patients. It was also noted that the MAC could be generated in vitro on cryostat sectioned normal human skin by pemphigus antibody in the presence of complement. Results of these studies suggest that complement activation may be related to membrane damage of epidermal cells in both PV and PF.

Complement Membrane Attack Complex↗
PubMed1989

Humoral immunopathological mechanisms in the skin.

Thus the skin is a unique organ in terms of location. Our skin directly interfaces with our environment and thus, unlike any other organ, is constantly subjected to foreign substances and microorganisms. Many of its structures are unique, and many of the proteins expressed by epidermal cells are also unique. Exposure to ultraviolet light affects the expression of some of these proteins as well as other biochemical substances. Although the skin also functions as an immunologic organ, it is not surprising that it can be the subject of immunologic attack. Thus, all of the major humoral immune mechanisms, cytotoxic or cytolytic, immune complex and atopic or anaphylactic, are manifested in terms of skin diseases.

Anaphylaxis↗
PubMed1988

Subclass distribution of human IgG autoantibodies in pemphigus.

The distribution of IgG subclasses in the intercellular substance (ICS) reactive autoantibodies in serum of 10 patients with pemphigus was analyzed by semiquantitative indirect immunofluorescence (IF) using the HP series of monoclonal antibodies specific for the four human IgG subclasses. IgG4 ICS specific autoantibody was present in all 10 sera at a titer of 10 to 320, while IgG1 antibodies were found in 9 of 10 sera at a seemingly lower level. IgG3 autoantibodies were detected in the serum of one patient, only after isolation of IgG using ion-exchange chromatography. Autoantibodies of IgG subclass 2 were not detectable in any of the 10 sera tested. One of the ten patients displayed circulating anti-ICS antibodies of only the IgG4 isotype.

Antibodies, Monoclonal↗
PubMed1988

Expression of pemphigus vulgaris antigen in cultured human keratinocytes: effect of inhibitors, tunicamycin, and lectins.

We have investigated expression of pemphigus vulgaris antigen(s) in cultured human keratinocytes induced by the addition of extracellular calcium. Cycloheximide (10(-4) M) inhibited pemphigus antigen expression and stratification but actinomycin D (2 micrograms/ml) had no effect. Tunicamycin, which inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues specifically, was used to study the role of glycosylation. When calcium switching was carried out in the presence of tunicamycin, human keratinocytes did not stratify, and the expression of pemphigus antigen was partially inhibited and limited to cell-cell contact areas. Analysis of biosynthetically labeled proteins showed that the synthesis of high-molecular-weight proteins was markedly reduced in the tunicamycin-treated cells. A reciprocal blocking test demonstrated that concanavalin A and wheat germ agglutinin receptor share an epitope with pemphigus vulgaris antigen(s). These results suggest that Ca++, newly synthesized protein, and N-asparaginyl glycosylation are required for normal pemphigus antigen expression and epidermal stratification in vitro. Pemphigus vulgaris antigen may have a highly glycosylated, high-molecular-weight protein chain with carbohydrates playing an important role in epidermal cell morphology, adhesion, and stability of cell surface antigens.

Anti-Bacterial Agents↗
PubMed1988

Complement fixation by pemphigus antibody. V. Assembly of the membrane attack complex on cultured human keratinocytes.

Previous studies have shown that pemphigus vulgaris (PV) IgG will fix early complement components (C1q, C4, and C3) to cultured murine epidermal cell surfaces and that PV IgG and complement alter epidermal cell membrane integrity. The present study was undertaken to determine if assembly of terminal complement components (C5, C6, C7, C8, and C9) and expression of C5b-9 neoantigens occur when PV IgG interacts with human keratinocyte (HuK) cell surface antigens in the presence of a source of complement. Monoclonal antibodies specific for C5, C6, C7, C8, C9, and C5b-9 neoantigens were screened for reactivity to the individual complement components in an assembled complex of human C5b-9 on rabbit red blood cell ghosts. Monoclonal antibodies (tissue culture supernatants) that bound to antigenic determinants accessible in the C5b-9 complex were selected for this study using immunofluorescence methods. HuK treated with PV IgG fixed C5, C6, C7, C8, C9, and C5b-9 neoantigens in a characteristic speckled pattern, while normal IgG did not. Heat inactivation or EDTA treatment of the complement source, or substitution of C2-depleted serum abolished C5, C6, C7, C8, C9, and C5b-9 neoantigen staining. PV IgG and complement also resulted in significant cytotoxicity to cell membranes as assessed using an ethidium bromide-fluorescein diacetate assay. These results suggest that PV IgG will activate the membrane attack complex of the complement system on HuK cell surfaces, resulting in cytotoxicity to cell membranes, further implicating complement in the pathogenesis of pemphigus.

Autoantigens↗
PubMed1988

Complement fixation by Brazilian Pemphigus foliaceus autoantibodies.

This study was undertaken to determine if Brazilian Pemphigus foliaceus (BPF) autoantibodies will fix complement as do P. vulgaris (PV) autoantibodies. When sections of human skin were examined following indirect immunofluorescence (IF) staining, BPF autoantibodies reacted with the upper layers of epidermis, while PV autoantibodies were reactive with the lower layers. When tissue culture epidermal cells were used for indirect IF, BPF autoantibodies were not detected after plating until 24 h, while PV autoantibodies reacted within 18 h of plating. Using complement IF staining methods, BPF autoantibodies were found to fix C1q, C4 and C3 to whole skin sections in an intercellular pattern and to the surface of cultured keratinocytes. Although reactive with different epidermal cell surface antigens, autoantibodies in BPF will fix complement in a fashion similar to autoantibodies in PV.

Animals↗
PubMed1988

Complement fixation by pemphigus antibody. IV. Enhanced epidermal cell detachment in the absence of human plasminogen.

It has been reportedly previously that complement enhances pemphigus vulgaris antibody-induced epidermal cell detachment. The present studies were designed to eliminate the possibility of the human plasminogen-plasmin system contributing to the cell detachment observed in previous complement-mediated studies. To assay for the presence of protease contamination in the reagents, a simple, sensitive, caseinolytic-fluorometric assay was used. Confluent murine or human epidermal cell cultures were incubated with pemphigus IgG with and without complement and plasminogen. Detached epidermal cells, as determined by light microscopy and cell-counter analysis, were enumerated at 48 hours. Incubating pemphigus IgG with complement resulted in marked cell detachment, compared with minimal cell detachment when pemphigus IgG was incubated with plasminogen. Culture media were collected after 48 hours and assayed for activation of plasminogen. It was determined that the added plasminogen had not been activated, particularly in experiments where significant detachment was observed. The plasminogen could still be activated by streptokinase and urokinase. These studies suggest that epidermal cell detachment in pemphigus appears to be mediated at least in part by complement activation.

Acantholysis↗