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Biomedical subjects

E H Beutner

Publications and source records attributed to E H Beutner.

At least 19 recordsLinked to original sources

A characteristic cutaneous direct immunofluorescent pattern associated with Ro(SS-A) antibodies in subacute cutaneous lupus erythematosus.

BACKGROUND: Antibodies to Ro(SS-A) are present in most patients with subacute cutaneous lupus erythematosus (SCLE). Patients with SCLE also have cutaneous immune deposits. However, no correlation of Ro(SS-A) antibodies with immune deposits in skin biopsy specimens has been described. OBJECTIVE: The purpose of this study is to describe characteristic direct immunofluorescence (IF) findings in 32 patients and their association with serum antibodies and clinical diagnosis. METHODS: Serum from patients with characteristic cutaneous direct IF findings was examined for antinuclear antibodies by indirect IF and for antibodies to ribonucleoprotein, Sm, Ro(SS-A), and La(SS-B) by gel immunodiffusion. RESULTS: Twenty-two of 32 patients who exhibited discrete speckled IgG staining predominantly, but not exclusively, of the basal cell cytoplasm had SCLE. Ro(SS-A) antibodies were identified in 23 of 26 patients and Ro(SS-A) and/or La(SS-B) in 25 of 26 patients. CONCLUSION: Direct IF staining characterized by discrete speckled IgG deposits in the basal cell cytoplasm is associated with Ro(SS-A) antibodies and SCLE.

Acute Disease

Differentiation of bullous pemphigoid from epidermolysis bullosa acquisita on frozen skin biopsies.

Patients with bullous pemphigoid and epidermolysis bullosa acquisita may have similar clinical, histologic, and routine immunohistologic features. These two diseases can be distinguished by routine diagnostic studies either on a patient's serum tested by indirect immunofluorescence on salt-split normal skin or by obtaining a fresh perilesional skin biopsy, inducing a split at the lamina lucida, and testing for the site of IgG deposition by direct immunofluorescence. Often the serum studies are negative, while direct immunofluorescent studies yield the characteristic linear IgG staining of the basement membrane zone. To eliminate the need for a repeat biopsy to make a laboratory differential diagnosis, we studied the efficacy of salt-splitting perilesional skin biopsies that had been previously submitted and frozen for routine direct immunofluorescent studies. The biopsies were thawed, salt-split, and processed for direct immunofluorescence. Three epidermolysis bullosa acquisita biopsies and seven bullous pemphigoid biopsies examined demonstrated IgG staining at sites consistent with their respective diagnoses. The IgG appeared in the dermal side of the split biopsies in epidermolysis bullosa acquisita and predominantly, or exclusively, in the epidermal side in bullous pemphigoid. Thus the direct immunofluorescent study of previously frozen and subsequently salt-split skin biopsies may be used for the differential diagnosis of bullous pemphigoid from epidermolysis bullosa acquisita. In most cases, it may eliminate the need for a repeat biopsy.

Basement Membrane

A distinct stratum corneum antigen in psoriasis and its reactions with stratum corneum autoantibodies.

Stratum corneum antibodies are ubiquitous and can be detected by various immunological methods. Of these, the ones detected by hemagglutination undergo changes in antibody titers and have been implicated in psoriasis. The purpose of our study was to examine if differences exist in the activities of the antigens isolated from psoriatic scales in comparison to normal callus. Stratum corneum antigens were prepared by trypsin-phenol-water extraction. The water phase, which contains the stratum corneum antigen, was used to sensitize the red blood cells in the hemagglutination assay. The antibody activity in human sera was determined before and after absorption with antigens isolated from callus, psoriatic scales, and cell envelopes. We found notable differences in the antigens obtained from callus and psoriatic scales. These include higher antibody titers to the antigens of the scales, the presence of unique antigenic determinants on psoriatic scales and the localization of the antigen on cell envelopes. These immunological differences were corroborated by the marked biochemical differences of certain amino acids, most notably glycine and proline, and these differences were unique to psoriatic scales as they were not shared with other hyperproliferative disorders.

Amino Acids

Quantitative studies of immunofluorescent staining. VII. Quantitative reference standard slide for standardization of fluorescence microscopes.

We evaluated a quantitative reference standard (QRS) slide with 10-microns beads with different concentrations of Coulter Electronics green dye No. 1. Microfluorospectrophotometric readings of the QRS slides provided quantitative comparisons between the sensitivity of the different fluorescence microscopes. The visual comparisons between beads with a range of intensities of fluorescence of Coulter Electronics green dye No. 1 indicated that the end points vary with different optical systems as do the end points in standard indirect immunofluorescent titrations. Fluorescent emission wavelength of QRS slide beads gave the same peak as fluorescein-labeled beads; both differed from the peak of orange beads of an 'Optical Standard' slide. Since shelf life studies show no changes in fluorescence intensity of beads over a period of 27 months or longer, QRS slide beads can afford a device for standardization of fluorescence microscopes used for immunofluorescent tests.

Animals

IgA pemphigus foliaceus with a clinical presentation of pemphigus herpetiformis.

A patient with clinical features of herpetiform pemphigus of the foliaceus type had histologic findings consistent with pemphigus. Intercellular IgA deposits in a pattern like that of IgG in pemphigus were present. Circulating pemphigus-type IgA-class antibodies reacted first only with guinea pig and later in the disease also with monkey esophagus sections. IgG-class pemphigus antibodies were blocked by the IgA-class antibodies of this patient. In addition, the IgA-class pemphigus antibodies in this patient were blocked by the IgG-class pemphigus antibodies in tests on guinea pig and monkey esophagus. This indicates that the IgA-class antibodies in this patient were directed either to the same antigen as the IgG-class pemphigus foliaceus antibodies or to one that is close enough to it to give steric hindrance. The skin lesions responded poorly to systemic corticosteroid therapy. Dapsone therapy initially produced dramatic improvement, but the condition flared to the point that plasmapheresis, in addition to high doses of corticosteroids and cyclophosphamide, had to be used to control it.

Acantholysis

Studies of laminin and type IV collagen in blisters of porphyria cutanea tarda and drug-induced pseudoporphyria.

Blisters from five patients with porphyria cutanea tarda and two patients with drug-induced pseudoporphyria were examined by direct immunofluorescence and by immunofluorescence mapping with antibodies against laminin and type IV collagen to determine the level of subepidermal separation. Primary screening by direct immunofluorescence revealed the characteristic immune deposits in the vessel walls of the upper dermal plexus in all cases and at the dermoepidermal junction in five of seven cases. Type IV collagen and laminin were reactive in six and five cases, respectively, and appeared in the floor of the bulla. The findings were identical in porphyria and pseudoporphyria. In one case in which the bullous pemphigoid antigen could be detected, it appeared in the epidermal roof of the bulla. These findings indicate that the split in porphyria and pseudoporphyria occurs in the lamina lucida. We propose that a multistep mechanism involved in the induction of blisters may be similar in porphyria and pseudoporphyria.

Autoantigens

In-vivo epidermal nuclear reactions: a selective process.

Epidermal in-vivo nuclear reactions of IgG occur primarily in patients with mixed connective tissue disease or systemic lupus erythematosus and have been associated with high titres of circulating antibodies to ribonucleoprotein (RNP). This study was carried out to examine whether these epidermal nuclear reactions are true or simply an excision artefact. We observed the epidermal nuclear reactions for IgG only and not for other immunoglobulins in both in-vivo and in-vitro organ-culture studies, despite the presence of antinuclear antibodies (ANA) of all immunoglobulin classes. The association of the in-vitro epidermal nuclear reactions with serum RNP antibodies, although not absolute was statistically significant. The absorption of the serum with extractable nuclear antigen (ENA) preparation diminished the nuclear reactivity on tissue explants. In addition, the penetration of ANA into the nuclei of skin explants was both time and temperature dependent and was inhibited by sodium azide and by oligomycin. We conclude that the epidermal nuclear staining reactions observed by direct immunofluorescence on skin biopsies is selective and that the penetration of IgG into the epidermal cell nuclei is an active process and not an artefact.

Antibodies

Studies on criteria of the European Academy of Dermatology and Venerology for the classification of cutaneous lupus erythematosus. I. Selection of clinical groups and study factors.

A group of 140 cases of various forms of lupus erythematosus (LE) were examined for 24 variables, including the 11 criteria of the American Rheumatism Association (ARA) for the classification of systemic lupus erythematosus (SLE), and 13 additional criteria suggested by the European Academy of Dermatology and Venerology (EADV) for studies of cutaneous LE with or without systemic involvement. The EADV study factors included skin histopathology and immunopathology, complement and IgG levels, and other laboratory tests, as well as selected clinical findings, most notably the papulosquamous and/or annular lesions that characterize subacute cutaneous LE (SCLE). The patients examined included 50 SLE, 35 SCLE, 30 discoid LE (DLE), 25 disseminated DLE (DDLE), and 17 polymorphous light eruption (PMLE) cases. Preliminary analyses of the data reveal the following: (1) The SCLE cases differed significantly from SLE, DLE, and DDLE in 10 of 11 ARA criteria (all but photosensitivity). (2) The frequencies of positive findings in SCLE also differed significantly for 11 of 13 EADV study factors. (3) While no significant differences appeared in the frequency of photosensitivity between the five study groups, photo-testing revealed significant increases in the frequency of persistence of the photo reactions for 10 days and their Koebnerization in the SCLE cases. (4) The presence of SS-A (Ro)/SS-B (La) antibodies had some predictive value for the appearance of systemic involvement in SCLE, as seen by the increased frequencies of five or more ARA criteria, although highly significant differences from SLE occurred in the absence of renal involvement and lower frequency of ANA and LE band test.(ABSTRACT TRUNCATED AT 250 WORDS)

Dermatology

Stratum corneum antibodies detected by hemagglutination are not directed against keratin intermediate filaments.

Autoantibodies to stratum corneum (SC) occur in virtually all normal adult human sera. These antibodies may be directed against various antigens of the SC. They have been detected by indirect immunofluorescence, passive hemagglutination (HA), immune adherence, and most recently by enzyme immunoassay and immunoblot methods. The purpose of our study was to examine whether antibodies to SC antigens as detected by passive HA are similar to the keratin intermediate filament (KIF) reactive antibodies. SC antigen preparation was prepared from psoriatic scales by the trypsin-phenol-water (TPW) extraction method. KIFs were prepared by 8 M urea extraction of normal callus or psoriatic scales. The anti-SC antibody titers of normal human sera were determined by passive HA before and after absorption with TPW-SC antigen preparation and upon absorption with KIFs. Similarly, titers of anti-KIF antibodies were determined on absorbed and unabsorbed sera by immunoblot assay. The results of this study indicate that the absorption of the sera with KIFs did not affect the titer of antibodies to TPW-extractable SC antigens whereas the titer of KIF antibodies dropped. KIF-reactive antibodies, on the other hand, were not affected by absorption with TPW-SC antigen, whereas the latter absorbed out the corresponding reactive antibodies. These results indicate that antibodies directed against SC antigen are different from the KIF-reactive antibodies.

Amino Acids

Chronic ulcerative stomatitis associated with a specific immunologic marker.

Four elderly women with chronic oral ulcerations are described. The lesions are chronic, erosive, or ulcerative; occur on the gingival, buccal, or lingual mucosa; and may occur in the form of desquamative gingivitis. The histopathologic findings are nondiagnostic. The disease is refractory to local and systemic corticosteroids, but treatment with hydroxychloroquine may be effective. Both in vivo binding to the oral mucosa and skin of a stratified epithelium-specific antinuclear antibody and high titers of these antibodies in serum are markers of this disease, which we refer to as chronic ulcerative stomatitis associated with stratified epithelium-specific antinuclear antibody.

Aged

Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita.

Bullous pemphigoid and epidermolysis bullosa acquisita may have indistinguishable clinical, histologic, and routine immunohistologic features. In those cases these two diseases can be reliably distinguished in routine diagnostic studies only in seropositive cases by tests on lamina lucida-split skin and in research studies by direct immunoelectron microscopy or, in patients with circulating autoantibodies, by immunoblotting studies. The use of these methods is limited by the expense and unavailability of the methods, the requirement for circulating autoantibodies, or both. We describe a method to distinguish between the two diseases on the basis of findings of direct immunofluorescence of a biopsy specimen after separation through the lamina lucida with 1.0 mol/L sodium chloride. The IgG appeared in the dermal side of the split specimens in epidermolysis bullosa acquisita and predominantly or exclusively in the epidermal side in pemphigoid. The method was found to be relatively simple, inexpensive, applicable to specimens preserved in transport media, and 100% reliable in our group of 22 patients.

Basement Membrane

Autoantibodies to nucleolar antigens in systemic scleroderma: clinical correlations.

Indirect immunofluorescence(IIF) and double immunodiffusion (DID) were performed on the sera of 64 patients who had a nucleolar immunofluorescence pattern on HEp-2 cells. Forty-nine of the sera were from 296 patients with systemic scleroderma (SSc) and 15 sera were from 214 patients with systemic lupus erythematosus (SLE). A homogeneous nucleolar staining pattern was found in 45 of the 64 sera (70.3%), a clumpy fluorescence associated with fibrillarin antibody in 14 (21.8%) and a speckled pattern was found in five of the sera (7.8%). There was a clear correlation between the sera which showed a homogeneous nucleolar staining pattern with symptoms of the polymyositis/scleroderma overlap syndrome that differed from SSc with concomitant myositis. The clumpy pattern was mainly associated with diffuse scleroderma and the speckled pattern with limited scleroderma (previously called acrosclerosis).

Adult

Immunology of celiac disease: tissue and species specificity of endomysial and reticulin antibodies.

Patients with celiac disease and dermatitis herpetiformis have circulating antibodies to reticulin and endomysium, the 'extracellular matrix' components as defined by their detection on rodent and primate tissues, respectively. Because both types of antibodies occur in both forms of gluten-sensitive enteropathy, studies were conducted to determine if the two types of antibodies can be distinguished by species and organ specificity. The results of these studies indicate that distinct endomysium-specific and reticulin-specific antibodies can be found and that these differ in their species specificity; i.e., endomysium antigen occurs in primate and not in rodent tissues while the reticulin antigen occurs in rodent and not in primate tissues. However, the activity of both endomysium and reticulin antibodies demonstrates similar tissue distribution, in that both react to antigens associated with gastrointestinal smooth muscles, peritubular and periglomerular areas of the kidney, and sinusoidal and periportal areas of the liver. Also, both antigens seem to be present in sheep and goat tissue. These studies indicate that the antigens reactive with endomysial antibodies are distinct from those reactive with reticulin antibodies.

Animals