摘要:

Because pemphigus vulgaris antigen (PVA) is homologous to desmogleins which are in desmosomes, we asked whether PVA is also localized to desmosomes. Immunogold electron microscopy was used to localize binding of PV antibodies. Rabbit antibodies raised against fusion proteins containing the extracellular portion of PVA bound to desmosomes of cultured keratinocytes. PV patient serum affinity-purified on one of these fusion proteins and injected into neonatal mice localized to separating desmosomes. These results show that PVA belongs to the desmoglein subfamily of cadherins according to sequence, localization and, presumably, function.

ISSN:1018-8665    

DOI:10.1159/000246923

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The 230-kD bullous pemphigoid antigen is a hemidesmosomal protein of the cutaneous basement membrane zone. We have previously cloned overlapping cDNAs corresponding to the human 230-kD bullous pemphigoid antigen gene (BPAG1), located at the human chromosomal locus 6p11–12. Utilizing the cDNA clones, a genomic DNA λFIX II phage library was screened. Seven overlapping genomic clones, spanning ∼20 kb, were isolated. These clones were shown to contain the entire ∼ 9-kb coding sequence of BPAG1 and it consisted of 22 separate exons which varied from 78 to 2,810 bp in size. Elucidation of 2.6 kb of 5′-flanking DNA was found to contain several putative transcriptional response elements, and development of promoter chloramphenicol acetyltransferase (CAT) reporter gene constructs allowed identification of putative cis-elements which confer keratinocyte-specific expression to the gene. In particular, a putative AP2-binding sequence (KRE2) in the position ––(1,786––1,778) was shown to be responsible for marked enhancement of the endogenous promoter, as well as of a heterologous thymidine kinase/CAT construct, activity in normal human keratinocytes. Normal human keratinocyte nuclear extracts contained a protein, designated as KTP1, which complexed with the KRE2 oligomer by gel mobility shift assays. UV cross-linking and Southwestern analysis suggested that KTP1 is a DNA-binding protein clearly distinct from AP2, and this protein may be responsible for the basal keratinocyte-specific expression o

ISSN:1018-8665    

DOI:10.1159/000246924

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Contrasting data have been reported about cardiovascular diseases in psoriatic patients. The aim of this study was therefore to evaluate blood coagulation and fibrinolysis in psoriatic patients. For this purpose, in a first group of 48 patients, we measured blood coagulation and fibrinolysis inhibitors [antithrombin III (AT), protein C (PC) and α2-antiplasmin (AP)], the products of thrombin and plasmin activity [fibrinopeptide A (FpA) and Bβ(15–42) (Bβ)], plasminogen (PLG) and fibrinogen (FBG). When all patients were considered we found a significant increase in Bβ and FpA levels, while PC, PLG and AP values were significantly decreased when compared to controls. FBG and AT were not different from the controls. In order to understand whether the observed abnormalities of blood coagulation and fibrinolysis were related only to psoriasis we divided all the patients into two groups: (1) patients with cardiovascular disease or other risk factors (n = 28) and (2) patients affected only by psoriasis (n = 20). Since no difference was observed between groups 1 and 2, we conclude that these findings are related to psoriasis. Subsequently we considered a different group of psoriatic patients. In these patients we measured FpA and two new thrombin activation indicators, such as prothrombin fragment 1 + 2 and thrombin-antithrombin complex (TAT). In addition we evaluated the levels of D-dimer, the product of the dissolution of cross-linking fibrin by plasmin. In this second group FpA, prothrombin fragment 1 + 2 and D-dimer were significantly higher than controls. Only TAT was not statistically different from those of the controls. The microvascular abnormalities of the psoriatic skin could play an important role in the activation of coagulation and fibrinolysis observed in psoriatic patients. Particularly the increase in the final products of blood coagulation and fibrinolysis (FpA, prothrombin fragments 1 + 2, Bβ and D-dimer) and the decrease in PC, PLG and AP could be interpreted as a subclinical consumption coagul

ISSN:1018-8665    

DOI:10.1159/000246755

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

An immunodominant and potentially pathogenic epitope associated with bullous pemphigoid (BP) and herpes gestationis (HG) has recently been mapped by our laboratory to a noncollagenous stretch of the extracellular domain of the human BP180 antigen. This antigenic site, designated the MCW-1 epitope, has been shown to be recognized by the majority of BP and HG sera. Interestingly, the MCW-1 epitope is absent from the murine BP180 molecule, and therefore, human autoantibodies directed against this site could not be tested for pathogenicity using the conventional passive transfer mouse model. Alternatively, rabbit antibodies were prepared against recombinant forms of the human MCW-1 epitope and the murine NC16A domain and were tested for pathogenicity by passive transfer experiments. Neonatal mice injected with rabbit antimurine BP180 IgG developed a subepidermal blistering disease that closely mimicked BP and HG at the clinical, histological and immunological levels. Rabbit IgG specific for the human MCW-1 epitope was not pathogenic. These results suggest that the autoantibodies against the MCW-1 epitope of the human BP180 antigen found in BP and HG sera may be relevant in the pathogenesis of blister formation in these patients.

ISSN:1018-8665    

DOI:10.1159/000246925

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Hemidesmosomes are subcellular structures that are involved in the attachment of a variety of epithelial cells, including basal epidermal keratinocytes, to the extracellular matrix. Like desmosomes, they provide a link between the intracytoplasmic keratin intermediate filaments and the plasma membrane. Major hemidesmosome plaque components include the bullous pemphigoid antigens of 230 and 180 kD and the α6β4-integrin. These transmembrane proteins may associate extracellularly with anchoring filament components including the 19-DEJ-1 proteoglycan and the polymeric proteins nicein/kalinin and epiligrin. Several of these hemidesmosome-related components have been implicated as targets for circulating auto-antibodies in immunobullous disorder

ISSN:1018-8665    

DOI:10.1159/000246926

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

In 481 patients with atopic dermatitis (AD), 4 major features of Hanifin and Rajka were found in 72%, and in 96% over 6 minor features were seen, which is much more than the minimum required by these authors for making a ‘firm diagnosis’. The incidence of particular minor features in all patients was varying significantly, and in subgroups of patients they appeared with different frequency. For example, asthma occurred more often in AD patients with the onset of skin lesions before the 6th month of life, and food intolerance was more frequently observed in patients with very high serum IgE level. In the control groups some minor features also occur but less frequently than in AD patients. We conclude that the anterior neck folds and Dennie-Morgan infraorbital fold should be regarded as minor AD featu

ISSN:1018-8665    

DOI:10.1159/000246781

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Eleven monoclonal antibodies were produced against the human N-terminal noncollagenous domain of type VII collagen. All antibodies were specifically bound to the epidermal basement membrane zone and did not cross-react with other dermal collagens. A binding of these antibodies was investigated with various species and revealed that the reactivities of each monoclonal antibody against rat, mouse, human and guinea pig skin differ from each other. These data may suggest that type VII collagen is antigenic to immunized small animals, i.e. the rat and mouse, and that threre are multiple antigenic determinants on type VII collagen.

ISSN:1018-8665    

DOI:10.1159/000246927

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

In this short review, we summarize the results of our recent studies on the effects of anti-bullous-pemphigoid antigen (BPA) antibodies and BP sera on the hemidesmosome in cultured keratinocytes (DJM-1 cells) as examined by immunofluorescence microscopy. The 180-kD and the 230-kD BPAs localized on the basal plasma membrane showed a homogeneously dotted pattern in cells grown with low Ca2+ (0.07 mM), while they formed a peculiar concentric ring or arch (ring/arch) pattern in cells grown with high Ca2+ (1.87 mM). In addition, the 180-kD BPA was distributed also on the lateral/apical cell membrane, and the 230-kD BPA was found in the cytoplasm. The high Ca2+ ring/arch arrangement of BPAs was formed within 3 h after the low-high Ca2+ switch. Anti-180-kD BPA monoclonal antibodies (MAbs) and BP sera, but not anti-230-kD BPA MAbs, which were added into this system, caused the internalization of the 180-kD BPA from the lateral/apical cell membrane and inhibited the formation of the ring/arch pattern. These results suggest that autoantibodies to the 180-kD, but not to the 230-kD, BPAs may directly bind to the antigen on the cell surface of the basal cells and disturb the formation of hemidesmosomes. The 180-kD BPA appears to be an initiator of blister formation.

ISSN:1018-8665    

DOI:10.1159/000246928

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Systemic amyloidosis is a rare disorder and usually occurs in aged persons with a poor prognosis. Certain mucocutaneous symptoms and signs may act as important clues for diagnosis. Skin or tongue biopsy may also provide important information to establish a firm diagnosis. During the past 14-year period, we found 19 cases of systemic amyloidoses: 8 (42%) with primary systemic amyloidosis, 8 (42%) associated with multiple myeloma and 3 (16%) were secondary amyloidosis. Ages of the patients ranged from 52 to 71 years with a mean age of 62 years at diagnosis. Median survival was only 8 months. Mucocutaneous manifestations were found in both primary type and myeloma-associated amyloidosis. In addition to the existence of amyloid in tongue and rectum biopsies in 17 cases and abdominal fat aspiration in 1 case, biopsies from clinically normal-looking skin also showed positive results in 18 out of 19 cases.

ISSN:1018-8665    

DOI:10.1159/000246782

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Pemphigoid gestationis (PG) is a rare auto-immune bullous disease of pregnancy that is characterized by linear deposition of C3 along the basal membrane zone of lesional, perilesional and uninvolved skin when examined by direct immunofluorescence. Circulating antibodies of IgGl class are also present. The aberrant expression of MHC class II molecules in the placenta appears to be important in triggering the immune response in the lamina lucida of the basement membrane zone in the placenta which then cross-reacts with the skin. PG appears to be unique in that it produces both basement membrane zone antibodies and anti-HLA antibodies. Chronic placental insufficiency can occur so that there is a clear tendency for premature deliveries and small-for-date babies. Secondary autoimmune disorders are significantly increased in PG and appear to be related to the HLA antigens DR3 and DR4. Finally abnormalities of complement polymorphism have recently been described.

ISSN:1018-8665    

DOI:10.1159/000246929

出版商:S. Karger AG    

年代:1994

数据来源: Karger