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Biomedical subjects

H Hintner

Publications and source records attributed to H Hintner.

At least 91 records · Page 5Linked to original sources
PubMed1984

KF-1 monoclonal antibody defines a specific basement membrane antigen defect in dystrophic forms of epidermolysis bullosa.

The monoclonal antibody, KF-1, identifies a noncollagenous constituent of the lamina densa of the basement membrane zone (BMZ) of skin. In order to determine whether this BMZ constituent is affected in epidermolysis bullosa (EB), a mechanobullous skin disease often resulting in marked disfigurement, we have examined skin from patients with various forms of this disease for binding by KF-1 as well as for binding by polyclonal antibodies to laminin, type IV collagen, and bullous pemphigoid antigen, three other known BMZ components of normal skin. In all specimens from patients with simplex and junctional forms of EB, all four antibodies bound normally. In contrast, absent or diminished KF-1 binding was noted in all skin specimens from patients with dystrophic EB; antibodies directed against the other BMZ constituents, however, bound normally. This suggests that KF-1 may play a role in the structural integrity of normal skin and its absence or diminution may be important in the pathogenesis of lesion formation in dystrophic EB.

Antibodies, Monoclonal↗
PubMed1984

Keratin intermediate filaments bear antigenic determinants for stratum corneum antibodies.

Stratum corneum (SC) antibodies are directed against antigens in the SC of the epidermis and are known to occur in all normal human sera. They have been shown by indirect immunofluorescence to be frequently associated with upper cytoplasmic (U-Cyt) antibodies. We have recently identified keratin intermediate filaments (KIF) as antigens for U-Cyt antibodies. In this study we investigated whether KIF also bear antigenic sites for SC antibodies. Normal human sera that contained SC and/or U-Cyt antibodies by indirect immunofluorescence were studied. Using immunoblot techniques 3 selected sera were shown to bind to high-molecular-weight (HMW) KIF proteins which had been extracted from 2 different epidermal cell preparations, that is, human callus or epidermis from which the SC had been removed by tape-stripping. The 3 test sera were absorbed on KIF which had been reconstituted in vitro from urea extracts from both epidermal substrates. As shown by indirect immunofluorescence, the SC and U-Cyt antibodies of all 3 sera were absorbed out with KIF from callus and with KIF from epidermis without SC. Immunoblot experiments, which are more sensitive than indirect immunofluorescence, demonstrated the absorption of anti-KIF protein antibodies of the 3 test sera on callus KIF and 2 of the sera on KIF obtained from epidermis without SC. This was shown by the lack of staining of the respective HMW KIF proteins with the postabsorption sera. With the third serum a marked reduction of antibody binding was found after absorption on KIF from epidermis without SC. These data indicate that KIF bear antigenic sites for SC antibodies.

Absorption↗
PubMed1984

[Eosinophilic spongiosis and ICS antibodies in a child with strophulus-like dermatosis].

Eosinophilic spongiosis associated with in vivo-bound antibodies to the epidermal intercellular space (ICS) were consistently observed in a recurrent strophulus-like eruption in an 11-year-old boy, thus suggesting pemphigus. The clinical course, however, ruled this diagnosis out since neither acantholysis nor the clinical picture of pemphigus developed in a period of 2.5 years. Since in vivo-bound ICS-antibodies have been described in several case reports of bullous impetigo we speculate that immune reactions to bacterial antigens may be involved in producing eruptions mimicking pemphigus vulgaris.

Autoantibodies↗
PubMed1984

[Systemic lupus erythematosus in hereditary complement 4 deficiency].

A genetically determined complete absence of the fourth component of complement, C4, associated with systemic lupus erythematosus has been detected in one member of another family. Observations made in this patient, the ninth described so far in whom systemic lupus erythematosus and C4 deficiency occur have confirmed that this condition presents with a characteristic clinical picture: there is pronounced sensitivity to sunlight and to cold with Raynaud's phenomenon; skin lesions are found predominantly in locations typical for subacute cutaneous lupus erythematosus and, remarkably, on the palms and soles. As was the case in two families described earlier, the C4-deficient gene was associated with the HLA-haplotype AW30, B18, DR7; BfS1.

Adult↗
PubMed1983

In vitro complement binding in human skin cells with altered differentiation.

Exposure of cytoskeletal intermediate-sized filaments (ISF) of various cell populations in normal human skin to normal human serum (NHS) results in the deposition of C3 upon these structures; this phenomenon most likely occurs antibody-independently, is initiated by Clq binding to ISF, and is followed by the activation of the classical complement pathway. In the present study we investigated the cytoplasmic C3-binding properties of skin cells undergoing altered differentiation. Incubation of cryostat skin sections of dermal melanocytic nevi with NHS and, subsequently, with fluorescein isothiocyanate-conjugated rabbit antihuman C3 resulted in a bright cytoplasmic staining of the vast majority of nevus cells. Immunoelectron microscopic studies demonstrated that ISF within nevus cells represented the only cytoplasmic C3-binding structures. In contrast, ISF within melanoma cells, basal cell carcinoma cells, and keratinocytes constituting psoriatic lesions lacked C3-binding properties. We propose that changes in structure and subunit protein composition of ISF in certain cells undergoing altered differentiation results in a decrease or loss of their C3-binding capacity.

Basal Cell Carcinoma↗
PubMed1983

Junctional blisters in acquired bullous disorders of the dermal-epidermal junction zone: role of the lamina lucida as the mechanical locus minoris resistentiae.

The level of cleavage was determined in a variety of acquired bullous diseases of the dermal-epidermal junction zone (bullous pemphigoid, dermatitis herpetiformis, porphyria cutanea tarda and epidermolysis bullosa acquisita). We used an indirect immunofluorescence technique to examine the basal membrane zone with anti-type IV collagen and anti-laminin antisera and bullous pemphigoid sera. The majority of blisters examined proved to be junctional, including those from disorders hitherto considered to be dermolytic. Dermolytic cleavage was encountered only sporadically in microvesicles of dermatitis herpetiformis, in one small vesicle and in one out of five large blisters of porphyria cutanea tarda and in a large lesion of epidermolysis bullosa acquisita. We conclude that in acquired bullous disorders of the dermal-epidermal junction zone the preferential site of split formation is the lamina lucida which appears to act as a locus minoris resistentiae; dermolytic split formation of substantial extent occurs only when the sublaminal fibrillar apparatus is mechanically compromised.

Blister↗
PubMed1983

Human upper epidermal cytoplasmic antibodies are directed against keratin intermediate filament proteins.

Upper cytoplasmic (U-Cyt) antibodies are directed against cytoplasmic antigens found in keratinocytes in the upper layers of the epidermis. Until now, they have been defined by indirect immunofluorescence and are known to occur in the sera of patients with cutaneous diseases such as bullous dermatoses, basal cell carcinomas, and melanomas. An increased incidence of U-Cyt antibodies has also been reported in the sera of patients with noncutaneous diseases, such as pulmonary neoplasms. They have been found in addition in the sera of some normal individuals. In this study we have identified keratin intermediate filaments (KIF) as antigens U-Cyt antibodies are directed against. KIF proteins were prepared, separated by polyacrylamide gel electrophoresis, transblotted to nitro-cellulose strips, and used as substrates for antibody binding. Sera containing U-Cyt antibodies by indirect immunofluorescence also had antibodies that were directed against high molecular weight (65,000, 63,000, 61,500) KIF proteins. When KIF proteins were separated according to their charge and their molecular weight by two-dimensional gel electrophoresis and transblotted, the anti-KIF protein antibodies bound to virtually all charge isomers of the KIF proteins at the respective molecular weight. The antibody titers measured using the transblotting technique were 10 to 160 times higher than those found by indirect immunofluorescence. To determine whether U-Cyt antibodies were directed against KIF, a series of absorption and elution experiments were performed. Absorption of test sera with purified KIF removed both U-Cyt antibodies and anti-KIF protein antibodies. Absorption with another type of intermediate filament derived from fibroblasts, vimentin, did not remove U-Cyt or anti-KIF protein antibodies. Absorbed U-Cyt and anti-KIF protein antibodies were both eluted from the same KIF preparation and shown to bind to U-Cyt antigens by indirect immunofluorescence and KIF proteins by transblotting. Absorption of a serum containing U-Cyt antibodies, anti-nuclear antibodies, and anti-basement membrane zone antibodies with purified KIF resulted in the removal of the U-Cyt antibodies but not the other types of antibody. In addition, all test sera, even those that lacked U-Cyt antibodies, were found to have low-titer antibodies against KIF proteins by the transblotting technique. These data indicate that KIF proteins bear antigens to which U-Cyt antibodies are directed and that low titer antibodies against KIF proteins may be much more common than previously appreciated.

Absorption↗
PubMed1983

[Livedo reticularis: dermatologic alarm signal in cold agglutinin disease].

A hitherto healthy adult man developed paroxysmal cold agglutinin disease following an infection of the upper respiratory tract with mycoplasma pneumoniae. Despite continuous blood exchange he died of massive intravascular hemolysis and uremia after 5 days. A presenting striking symptom of this rapidly fatal disease was the acute onset of generalized livedo reticularis. The disease was caused by the rare anti Pr-cold agglutinins which are capable of eliciting hemolysis even in low titers and, in the present case, at body temperature.

Adult↗
PubMed1982

Systemic lupus erythematosus in hereditary deficiency of the fourth component of complement.

Three patients from two families with complete hereditary deficiency of the fourth component of complement (C4) and systemic lupus erythematosus are described. The syndrome presented by these patients is characterized by early onset in life; exquisite sensitivity to sunlight and to cold exposure, the latter resulting Raynaud's phenomenon; and skin lesions involving not only exposed areas of the body but also palms and soles and presenting as butterfly rashes, maculopapular eruptions, and lesions similar to those of chronic discoid lupus erythematosus, with marked scaling, atrophy, and scarring. Lupus erythematosus (LE) cell tests were negative and antinuclear antibody (ANA) titers low or negative. The male patient of our series died at the age of 31/2 years from septicemia, whereas the two girls, aged 18 and 11 years, respectively, were alive at the time of writing. The C4-deficient gene is associated with HLA-Aw32, Bw38, and Bf S in one family and with HLA-A30, B18, DR7, and Bf S1 in the other family; the latter is the second family in which this HLA haplotype has been found to be associated with hereditary C4 deficiency.

Adolescent↗
PubMed1982

In vitro complement binding on cytoplasmic structures in normal human skin: immunoelectronmicroscopic studies.

We have previously provided evidence that suggests that exposure of cryostat skin sections to normal human serum (NHS) results in the antibody-independent Clq binding to cytoplasmic structures of various cell types, leading to classical complement pathway activation as evidenced by cytoplasmic C3 deposition. In the present study, we have employed immunoelectronmicroscopic methods to clarify the exact nature of cytoplasmic C3 binding structures. Incubation of cryostat skin sections with NHS followed by peroxidase-labeled rabbit anti-human C3 serum (HRP-R/Hu C3) revealed that intracytoplasmic binding of C3 occurred in suprabasal keratinocytes, melanocytes, fibroblasts, smooth muscle cells, endothelial cells, pericytes, Schwann cells, and nerve axons, but not in basal keratinocytes, Langerhans cells, and other cellular constituents of the skin. C3 binding, as revealed by the deposition of HRP reaction product, was exclusively confined to intermediate-sized filaments (ISF), which can therefore be considered to represent the subcellular site for classical complement pathway activation. Under experimental conditions that do not allow classical complement pathway activation, ISF were not decorated. Our observation that ISF of ontogenetically different cell types share the capacity of complement fixation is in accordance with the recent finding that different ISF types, despite their biochemical and antigenic heterogeneity, have common alpha-helical domains and may provide a clue to the mechanism and site of interaction between complement components and ISF.

Axons↗
PubMed1982

[Epidermolysis bullosa acquisita: diagnosis by optic immunofluorescent demonstration of junctional antigens and vitamin E treatment].

In a patient with epidermolysis bullosa acquisita the characteristic dermolytic cleavage was demonstrated by electron microscopy and by mapping of antigenic determinants (type IV collagen, laminin, bullous pemphigoid antigen) of the dermal-epidermal junction. The latter method represents a rapid and reliable way to determine the cleavage plane in diseases which display subepidermal blister formation at the light-microscopic level. The classification of epidermolysis bullosa acquisita is still under dispute. Due to its highly characteristic clinical, ultrastructural, and immunologic features and pending further experimental data, epidermolysis bullosa acquisita should be regarded as a separate disease entity; its lumping together with cicatricial pemphigoid, as proposed by some authors appears speculative. Therapy of epidermolysis bullosa acquisita is generally regarded as difficult; following a 3-year course of high dose vitamin E therapy our patient underwent complete clearing; the possibility of a spontaneous remission, on the other hand, cannot be unequivocally ruled out.

Adult↗
PubMed1982

Generalized atrophic benign epidermolysis bullosa.

Eight cases of a new variant of hereditary epidermolysis bullosa (EB), generalized atrophic benign EB, are reported. This is a junctional form of EB that, in contrast to EB letalis of Herlitz, has a good prognosis. It is inherited as an autosomal recessive trait, and the clinical picture is monotonously similar in all patients observed so far, with generalized blister formation, atrophic alopecia, and dystrophic nail changes. Blisters on the skin and mucous membranes heal without scarring or dystrophy but often result in notable atrophy. There is a definite tendency for amelioration of symptoms as the patients age, but therapy has, so far, been ineffective.

Adolescent↗