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Biomedical subjects

L H Morrison

Publications and source records attributed to L H Morrison.

6 recordsLinked to original sources

When to request immunofluorescence: practical hints.

This review highlights important considerations in obtaining good skin biopsy specimens to optimize results of direct immunofluorescence (IF) studies and also summarizes the various patterns of cutaneous IF deposition and their associated diagnoses. IF findings of immunobullous diseases, lupus erythematosus, vasculitis, lichen planus, and erythema multiforme are included. The uses of indirect IF studies are also reviewed including newer modifications that are valuable in helping to diagnose epidermolysis bullosa acquisita and paraneoplastic pemphigus.

Basement Membrane↗

Bullous and cicatricial pemphigoid.

Bullous pemphigoid (BP) and cicatricial pemphigoid are blistering mucocutaneous diseases characterized by detachment of the overlying epithelium from its stroma. IgG and complement components are deposited in all affected tissue at the level of blister formation--through the lamina lucida of the epithelium. The primary antibody response is of the IgG 4 subclass, and the antigens recognized by these autoantibodies have been shown to be 230 kD and 180 kD transmembrane proteins unique to the hemidesmosome of stratified squamous epithelial cells. Although it is suspected that these antigens are important in cell-substrate adhesion, this has not been proven. Stanley et al. have recently defined the sequence of a portion of the C terminal end of the 230 kD antigen and Diaz et al. have isolated a cDNA encoding for the 180 kD antigen. Structural data regarding these antigens should prove critical to definition of their presumed function. Therefore, BP is felt to be an autoimmune disease where the cutaneous lesions may solely be a consequence of binding of these antihemidesmosome autoantibodies to the specific antigen, but definitive proof of this assumption is incomplete.

Autoantibodies↗

Herpes gestationis.

Herpes gestationis is a rare, self limited bullous disease of pregnancy and the post-partum period with a presumed autoimmune basis. It is characterized clinically by pruritic, urticarial and vesiculobullous lesions, histologically by subepidermal vesicle formation, and immunopathologically by deposition of immunoreactants along the basement membrane zone. These features are shared by bullous pemphigoid which suggests that herpes gestationis may be a related entity. Immunoblotting studies have shown that herpes gestationis sera recognize a 180 kD epidermal antigen; in comparison, bullous pemphigoid sera most often detect a 220-240 kD antigen, but a significant number also recognize a 180 kD epidermal antigen, suggesting immunological similarities between these two diseases. Etiology and pathophysiology are not established, but an immunological basis is implicated by the frequent finding of C3 along the basement membrane zone of perilesional skin, the presence of herpes gestationis factor, increased incidence of HLA-DR3 and HLA-DR4, and association with other putative autoimmune diseases. Treatment usually consists of systemic corticosteroids.

Autoantigens↗

Definition of bullous pemphigoid antibody binding to intracellular and extracellular antigen associated with hemidesmosomes.

Bullous pemphigoid (BP) antibodies are deposited predominantly in the lamina lucida in vivo; however, circulating BP antibodies bind in vitro to the cytoplasmic plaque of basal cell hemidesmosomes. We examined the ability of IgG in nine BP sera to bind to intracellular or extracellular antigen. On skin cryosections, indirect IF showed IgG bound to basement membrane zone (BMZ) and indirect ImmunoEM confirmed intracellular binding on the cytoplasmic plaque of hemidesmosomes. In contrast, when normal skin was exposed to BP serum in organ culture, direct IF showed fainter linear deposition of IgG along the BMZ, and direct ImmunoEM demonstrated extracellular IgG binding in the lamina lucida, predominantly beneath hemidesmosomes. Four of nine sera showed complement fixation on indirect IF samples (IgG bound to intracellular antigen) and three showed complement fixation on direct IF specimens (IgG bound to extracellular antigen). Three of the nine sera contained complement fixing antibodies detectable only in antibody populations specific for intracellular or extracellular antigen. Western immunoblots showed that five of nine sera recognized a 240-kD protein and four of nine recognized a 180-kD protein. There was no correlation between the presence (or absence) of either band and the detection of complement fixing antibodies specific for intracellular or extracellular antigen. BP autoantibodies bind both intracellular and extracellular antigen, and IgG binding exclusively to extracellular antigen that mimics the in vivo situation can be detected by using organ culture. Complement fixation may be restricted to antibodies specific for intracellular or extracellular antigen. These findings underscore the complexity of the autoantibody-antigen system in BP and have implications regarding the proposed pathogenicity of the autoantibodies.

Antigen-Antibody Reactions↗

Persistence of an allergen in hair after glyceryl monothioglycolate-containing permanent wave solutions.

Glyceryl monothioglycolate, a reducing agent used in permanent waving solutions, is a recognized cause of allergic contact dermatitis. Because of an unexplained persistence of dermatitis in beauty shop clients after exposure to permanent wave solutions containing glyceryl monothioglycolate, we looked for the presence of this or a cross-reacting substance in permanent-waved hair as a possible source of continued exposure to the allergen. Seventeen subjects sensitive to glyceryl monothioglycolate underwent patch testing with hair samples collected before and at various times after a permanent wave containing glyceryl monothioglycolate. None reacted to hair that had not received a permanent, while 7 of 17 showed positive reactions to the permanent-waved hair. Positive reactions were seen in hair collected as long as 3 months after the permanent. This suggests that a glyceryl monothioglycolate-related allergen is retained in hair for up to 3 months after the permanent, which may explain the long-lasting dermatitis that occurs in clients sensitive to glyceryl monothioglycolate.

Adult↗

Herpes gestationis autoantibodies recognize a 180-kD human epidermal antigen.

Herpes gestationis (HG) is a putative autoimmune bullous dermatosis of pregnancy which shares many findings with bullous pemphigoid (BP), a disease of the elderly. This study identifies for the first time the antigen detected by HG autoantibodies and compares it with that recognized by BP autoantibodies. Sera from 16 HG and 17 BP patients, and from normal pregnant women were evaluated by immunofluorescent (IF) studies and immunoblotted against human epidermal extracts. 89% of HG sera with circulating antibodies by IF recognized a 180-kD protein by immunoblotting. 71% of BP sera recognized a 240-kD band, but 47% detected a 180-kD protein that comigrated with the antigen detected by HG sera. None of the control sera recognized any specific bands. These findings suggest that the 180-kD epidermal protein may be the antigen detected by the HG factor and they also define immunologic similarities between HG and BP.

Autoantibodies↗