PubMed Health⌕ Search

Biomedical subjects

R Kirnbauer

Publications and source records attributed to R Kirnbauer.

At least 19 recordsLinked to original sources
PubMed2003

230-kDa and 190-kDa proteins in addition to desmoglein 1 as immunological targets in a subset of pemphigus foliaceus with a combined cell-surface and basement membrane zone immune staining pattern.

Pemphigus erythematosus, initially described as a combination of pemphigus with lupus erythematosus, and pemphigus foliaceus are now frequently considered localized and generalized variants of superficial pemphigus. Yet diagnostic criteria for pemphigus erythematosus remain controversial. Distinct from pemphigus foliaceus, pemphigus erythematosus displays immune depositions at the dermal-epidermal junction, which suggests additional immunopathological mechanisms. We present three patients with clinical and histopathologic signs of superficial pemphigus, who all exhibited an immunomorphology characteristic of pemphigus erythematosus. Complement depositions in a granular-linear fashion were consistently found at the dermal-epidermal junction besides in vivo bound and circulating antikeratinocyte cell-surface autoantibodies. Histopathology showed subcorneal acantholysis, and all sera contained antidesmoglein 1 but not antidesmoglein 3 autoantibodies detected by enzyme-linked immunosorbent assays (ELISA). Additional autoantibodies against a 230-kDa protein and against a 190-kDa protein comigrating with bullous pemphigoid antigen 1 (BP230) and periplakin, respectively, were present in all the patients' sera. As two sera specifically reacted with BP230 by ELISA, the presence of BP230-specific autoantibodies could be associated with dermal-epidermal immune staining in these patients. In pemphigus erythematosus, dermal-epidermal immune staining is generally attributed to the deposition of immune complexes, while the presence of BP230-specific autoantibodies has not been reported in this disease previously. Perhaps, the unique autoantibody profile of the patients in the study permits discrimination between patients with superficial pemphigus that display additional dermal-epidermal immune staining from those with conventional pemphigus foliaceus on a molecular basis. Further studies will be required to substantiate the frequency of this occurrence and to unravel its pathogenic significance.

Adult↗
PubMed1999

Desmoglein 3-ELISA: a pemphigus vulgaris-specific diagnostic tool.

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies against desmoglein 3 (Dsg3), an epidermal desmosomal adhesion protein of the cadherin family. Cloning of the Dsg3 gene and expression of the protein in a native conformation enabled the recent development of a specific and sensitive enzyme-linked immunosorbent assay (ELISA) for the detection of PV autoantibodies. OBJECTIVES: To evaluate serum samples from patients with PV and other dermatologic diseases for anti-Dsg3 antibodies. To compare ELISA values with autoantibody titers obtained by classic indirect immunofluorescence (IIF). DESIGN: Serum samples from patients with PV and various other bullous and nonbullous skin diseases were tested for anti-Dsg3 reactivity by ELISA. SETTING: Ambulatory and hospitalized patients from a university hospital. PATIENTS: Fifty-two serum samples from 11 patients with PV, and serum samples from 11 patients with bullous pemphigoid, 12 patients with other bullous diseases, 22 patients with various nonbullous skin disorders, and 10 healthy individuals were tested. RESULTS: Forty-seven (98%) of 48 serum samples from patients with PV that were positive by IIF on monkey esophagus were also reactive by Dsg3-ELISA, whereas 4 of 4 IIF-negative PV serum samples showed no reactivity by ELISA. In addition, negative ELISA results were obtained from 11 of 11 serum samples from patients with bullous pemphigoid, 10 of 12 serum samples from patients with other bullous skin disorders, 7 of 9 serum samples from patients with autoimmune-connective tissue diseases, and 13 of 13 serum samples from patients with other nonbullous skin diseases. Interestingly, 1 patient with paraneoplastic pemphigus had positive ELISA results. There was a positive correlation (r = 0.654) between ELISA values and IIF titers within the whole population with PV. In addition, when multiple serum samples from 1 patient with PV sampled over a 2-year period were tested, ELISA reactivity paralleled both the IIF titers and the clinical course. CONCLUSION: The Dsg3-ELISA is a sensitive, objective, and PV-specific test that should be considered as an adjunct test for the management of patients with PV.

Adult↗
PubMed1999

Anaplastic squamous cell carcinoma (SCC) in a patient with chronic cutaneous graft-versus-host disease (GVHD).

We describe an allogeneic bone marrow (BM) recipient who developed aggressive, metastasizing squamous cell cancer (SCC) of the skin, and discuss possible risk factors in the development of this secondary solid tumor. The patient had been treated with cyclosporine (CsA), methyl-prednisolone and thalidomide for 3 years because of extensive de novo chronic cutaneous GVHD occurring 1 year after BMT. Ten years after BMT a locally invasive and metastasizing SCC occurred on the patient's neck, and diagnosis was confirmed by H&E histopathology and cytokeratin-immunohistochemistry. Analysis of genomic DNA did not reveal p53 mutations nor were HPV sequences detectable. Risk factors included conditioning for BMT with total body irradiation (TBI) and cyclophosphamide (Cy), immunosuppressive treatment for GVHD, and extensive exposure to UV radiation before and after BMT. Despite surgery and adjuvant chemotherapy with 5-fluorouracil (5-FU) the patient died 1 year after the diagnosis of SCC.

Adult↗
PubMed1999

Seroreactivity to human papillomavirus types 16, 18, 31, and 45 virus-like particles in a case-control study of cervical squamous intraepithelial lesions.

Serum IgG antibodies to human papillomavirus (HPV) types 16, 18, 31, and 45 virus-like particles were measured in a nested case-control study of cervical squamous intraepithelial lesions. HPV-16 seroreactivity was strongly associated with HPV-16 DNA detection (odds ratio, 9.0; 95% confidence interval, 4.4-19.4), and similar type specificity was observed for HPV-31 and -45. In contrast, seroreactivity to any type was associated with elevated seroreactivity to all others. Among cases and controls, HPV-16 showed the highest seroprevalence, with 23.8% of 80 cases and 10.5% of 258 controls seroreactive to HPV-16 alone, and another 27.5% and 5.4%, respectively, seroreactive to HPV-16 plus other types. Overall, 24 (30.0%) cases and 17 (6.6%) controls were seroreactive to multiple types. These data suggest that seroreactivity to a given type reflects mainly type-specific HPV infection as measured by DNA detection and may also signal past exposure to other types that are now only serologically detected.

Antibodies, Viral↗
PubMed1998

Chimeric papillomavirus virus-like particles elicit antitumor immunity against the E7 oncoprotein in an HPV16 tumor model.

Papillomavirus-like particles (VLPs) are a promising prophylactic vaccine candidate to prevent human papillomavirus (HPV) infections and associated epithelial neoplasia. However, they are unlikely to have therapeutic effects because the virion capsid proteins are not detected in the proliferating cells of the infected epithelia or in cervical carcinomas. To increase the number of viral antigen targets for cell-mediated immune responses in a VLP-based vaccine, we have generated stable chimeric VLPs consisting of the L1 major capsid protein plus the entire E7 (11 kDa) or E2 (43 kDa) nonstructural papillomavirus protein fused to the L2 minor capsid protein. The chimeric VLPs are indistinguishable from the parental VLPs in their morphology and in their ability to agglutinate erythrocytes and elicit high titers of neutralizing antibodies. Protection from tumor challenge was tested in C57BL/6 mice by using the tumor cell line TC-1, which expresses HPV16 E7, but not the virion structural proteins. Injection of HPV16 L1/L2-HPV16 E7 chimeric VLPs, but not HPV16 L1/L2 VLPs, protected the mice from tumor challenge, even in the absence of adjuvant. The chimeric VLPs also induced protection against tumor challenge in major histocompatibility class II-deficient mice, but not in beta2-microglobulin or perforin knockout mice implying that protection was mediated by class I-restricted cytotoxic lymphocytes. These findings raise the possibility that VLPs may generally be efficient vehicles for generating cell-mediated immune responses and that, specifically, chimeric VLPs containing papillomavirus nonstructural proteins may increase the therapeutic potential of VLP-based prophylactic vaccines in humans.

Animals↗
PubMed1998

Absence of p53 protein overexpression in precancerous lesions of the vulva.

BACKGROUND: Recently the authors reported the prognostic value of p53 protein overexpression in invasive squamous cell carcinoma of the vulva. The aim of this study was to evaluate the status of p53 overexpression and human papillomavirus (HPV) infection in patients with precancerous lesions of the vulva. METHODS: Biopsy specimens of 28 women (mean age, 44.2 years; range, 19-71 years) with warty and/or basaloid type vulvar intraepithelial neoplasia (VIN) of Grade 1 to 3 were examined retrospectively for p53 protein overexpression by immunohistochemistry. The presence of the HPV genome was assessed using a nested polymerase chain reaction (PCR) method with consensus primers directed against the L1 coding region. RESULTS: Neither the preoperative punch biopsy specimen nor the subsequent surgical specimen contained immunohistochemically detectable levels of p53 in this study of a group of younger women with preinvasive vulvar lesions. These results are in contrast to those obtained previously in older women with keratinizing squamous cell carcinoma demonstrating p53 protein overexpression in approximately 50% of patients. HPV DNA was detected in the vast majority of VIN cases (92.8%) using a highly sensitive nested PCR method. The current data indicate that p53 protein is not overexpressed in basaloid/warty VIN when evaluated by immunohistochemistry. In addition, this study confirms previous reports demonstrating the presence of HPV DNA in the majority of these lesions. CONCLUSIONS: These data suggest that p53 protein overexpression is not an early event in the pathogenesis of basaloid/warty type vulvar dysplasia and that HPV infection may contribute to the development of VIN.

Adolescent↗
PubMed1998

[Cicatricial pemphigoid with autoantibodies to laminin 5 (epiligrin) in a patient with metastatic endometrial carcinoma].

A 71-year-old female patient presented with erosions of the oral, genital and ocular mucosa, but without skin lesions. One year prior to the onset of lesions, a metastatic adenocarcinoma of the endometrium had been diagnosed. In perilesional skin, direct immunofluorescence showed linear deposits of C3 and IgG along the basement membrane zone. Indirect immunofluorescence demonstrated anti-basement membrane zone antibodies which bound exclusively to the dermal side of 1M NaCl-split skin. In immunoprecipitation studies, the autoantibodies bound a set of proteins characteristic of epiligrin/laminin-5, and they specifically immunoblotted the alpha-subunit of this protein. These results confirmed our presumed diagnosis of anti-epiligrin cicatricial pemphigoid. Combined treatment with methylprednisolone and dapsone resulted in prompt remission, despite progression of her malignancy. So far, only eight patients with anti-epiligrin cicatricial pemphigoid have been reported worldwide. Our patient represents the first case from Austria and is clinically and immunopathologically similar to previously reported cases.

Adenocarcinoma↗
PubMed1997

Characterization of a human papillomavirus type 16 variant-dependent neutralizing epitope.

We have determined that three type-specific and conformationally dependent monoclonal antibodies, H16.E70, H16.U4, and H16.V5, neutralize pseudotype human papillomavirus type 16 (HPV16) virions in vitro. H16.U4 and H16.V5 neutralized pseudotype virions derived from the German HPV16 variant 114K and the Zairian variant Z-1194 with equal efficiency. In contrast, neutralization of Z-1194 pseudotype virions by H16.E70 was two orders of magnitude weaker than neutralization of 114K pseudotype virions. This difference correlated with enzyme-linked immunosorbent assay reactivity of H16.E70 to L1 virus-like particles of the two variants. A substitution at residue 282 of L1 was responsible for this differential reactivity, suggesting that this residue constitutes part of the H16.E70 epitope.

Antibodies, Monoclonal↗
PubMed1996

Seroreactivity to HPV16 virus-like particles as a marker for cervical cancer risk in high-risk populations.

Sexually transmitted genital human papillomavirus (HPV) infection, most often HPV 16, is considered the major etiologic determinant of cervical cancer. However, some studies have found relatively low prevalences of genital tract HPV DNA in some geographical areas, such as Greenland, that have high rates of cervical cancer. We sought to evaluate HPV 16 infection in high-risk cohorts using a serologic assay that assesses prior exposure as well as current infection and to compare the results with those obtained using a sensitive PCR-based HPV DNA assay. An ELISA based on HPV 16 virus-like particles was used to detect IgG serum antibodies in women attending sexually transmitted disease (STD) clinics in Nuuk, Greenland and Copenhagen, Denmark. Using a preassigned cut-off, 56% of Greenlandic and 41% of Danish women were seropositive (p = 0.02). In Greenlandic women, there was a non-significant increase in seropositivity with age, and odds ratios for seropositivity were similar for women with more than 5 lifetime sex partners. Seropositivity in the Danish women, however, increased linearly with increases in these 2 factors, which are likely correlates of lifetime exposure to genital HPVs. In contrast, any genital HPV DNA (HPV16 specifically) was detected in 24% and 36% of Greenlandic and Danish women, respectively and was most frequently detected in women below 20. The finding that HPV DNA prevalences, unlike seroprevalences, tended to decrease with increased lifetime risk of infection, provides an explanation for the lack of correlation between HPV DNA prevalences and cervical cancer risk in previous studies of high-risk populations.

Adult↗
PubMed1996

Virus-like particles of bovine papillomavirus type 4 in prophylactic and therapeutic immunization.

Virus-like particles were produced in insect cells containing either the L1 and L2 capsid proteins of bovine papillomavirus type 4 (BPV-4) or only the L1 protein. Both preparations of VLPs proved to be extremely effective prophylactic vaccines. Thirteen of 15 calves immunised with either L1-L2 VLPs or L1-VLPs were refractory to experimental challenge with high doses of BPV-4 and did not develop papillomas, while 9 of 10 control animals developed multiple oral papillomas. VLPs were not efficient as therapeutic vaccine in calves with established papillomas, although VLP-vaccinated animals appeared to undergo tumour regression more rapidly than nonvaccinated control animals. Antibody responses in VLP-vaccinated calves were associated with prevention of disease but not with regression of papillomas. Thus prophylactic VLP vaccination is effective in preventing disease in this model of mucosal papillomavirus infection. VLPs and native virus share at least some conformational epitopes, as shown by the cross-reactivity of their antibodies.

Animals↗
PubMed1996

Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study.

OBJECTIVE: To study human papillomavirus type 16 in the aetiology of cervical carcinoma. DESIGN: Within a cohort of 18814 Finnish women followed up to 23 years a nested case-control study was conducted based on serological diagnosis of past infection with human papillomavirus type 16. SUBJECTS: 72 women (27 with invasive carcinoma and 45 with in situ carcinoma) and 143 matched controls were identified during the follow up. MAIN OUTCOME MEASURE: Relative risk of cervical carcinoma in presence of IgG antibodies to human papillomavirus type 16. RESULTS: After adjustment for smoking and for antibodies to various other agents of sexually transmitted disease, such as herpes simplex virus type 2 and Chlamydia trachomatis, the only significant association was with infection with human papillomavirus type 16 (odds ratio 12.5; 95% confidence interval 2.7 to 57, 2P<0.001). CONCLUSION: This prospective study provides epidemiological evidence that infection with human papillomavirus type 16 confers an excess risk for subsequent development of cervical carcinoma.

Adolescent↗
PubMed1996

Epidemiologic determinants of seroreactivity to human papillomavirus (HPV) type 16 virus-like particles in cervical HPV-16 DNA-positive and-negative women.

The epidemiologic determinants of seroreactivity to human papillomavirus (HPV) type 16 L1/L2 virus-like particles (VLPs) were assessed separately in HPV-16 DNA-positive and -negative women participating in a nested case-control study of incident cervical neoplasia. Seventy-four women with cervical HPV-16 DNA and 656 cytologically normal HPV-16 DNA-negative subjects were interviewed and tested at two time points for viral DNA and once (at the later time) for VLP seroreactivity. Among subjects who were currently HPV-16 DNA-negative, seroreactivity odds ratios increased from 2.9 for 2-5 male sex partners (vs. 0 or 1) to 5.4 for 6-9 partners and 14.0 for > or = 10. Thus, prior cervical infection may be a major determinant of seroreactivity in HPV-16 DNA-negative women. This trend was not observed in HPV-16 DNA-positive subjects. Seroreactivity was independently associated with oral contraceptive use, particularly in HPV-16 DNA-negative subjects with use for > or = 10 years. Consequently, a possible role for virus-steroid hormone interactions in seroconversion is suggested.

Antibodies, Viral↗
PubMed1996

Assessment of the serological relatedness of genital human papillomaviruses by hemagglutination inhibition.

To assess the potential for cross-protection among genital human papillomavirus (HPV) types in virus-like particle (VLP)-based vaccinations, inhibition of HPV VLP-mediated hemagglutination by rabbit antisera raised against HPV type 6b (HPV-6b), HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, and HPV-45 was analyzed. Only highly homologous types (HPV-6b and HPV-11, and HPV-18 and HPV-45) exhibited detectable serological cross-reaction for the class of antibodies that inhibit virion-to-cell surface binding. However, analysis of neutralizing monoclonal antibodies to several animal and human papillomaviruses indicated that over half of these antibodies do not prevent cell surface binding, but these latter antibodies do not appear to be more cross-reactive in enzyme-linked immunosorbent assays than those that mediate inhibition of hemagglutination. The data strongly suggest that while there may be limited cross-protection between highly (>85% L1 amino acid identity) homologous types, protection by HPV VLP-based vaccines will be predominantly type specific.

Animals↗
PubMed1996

In vitro generation and type-specific neutralization of a human papillomavirus type 16 virion pseudotype.

We report a system for generating infectious papillomaviruses in vitro that facilitates the analysis of papillomavirus assembly, infectivity, and serologic relatedness. Cultured hamster BPHE-1 cells harboring autonomously replicating bovine papillomavirus type 1 (BPV1) genomes were infected with recombinant Semliki Forest viruses that express the structural proteins of BPV1. When plated on C127 cells, extracts from cells expressing L1 and L2 together induced numerous transformed foci that could be specifically prevented by BPV neutralizing antibodies, demonstrating that BPV infection was responsible for the focal transformation. Extracts from BPHE-1 cells expressing L1 or L2 separately were not infectious. Although Semliki Forest virus-expressed L1 self-assembled into virus-like particles (VLPs), viral DNA was detected in particles only when L2 was coexpressed with L1, indicating that genome encapsidation requires L2. Expression of human papillomavirus type 16 (HPV16) L1 and L2 together in BPHE-1 cells also yielded infectious virus. These pseudotyped virions were neutralized by antiserum to HPV16 VLPs derived from European (114/K) or African (Z-1194) HPV16 variants but not by antisera to BPV VLPs, to a poorly assembling mutant HPV16 L1 protein, or to VLPs of closely related genital HPV types. Extracts from BPHE-1 cells coexpressing BPV L1 and HPV16 L2 or HPV16 L1 and BPV L2 were not infectious. We conclude that (i) mouse C127 cells express the cell surface receptor for HPV16 and are able to uncoat HPV16 capsids; (ii) if a papillomavirus DNA packaging signal exists, then it is conserved between the BPV and HPV16 genomes; (iii) functional L1-L2 interaction exhibits type specificity; and (iv) protection by HPV virus-like particle vaccines is likely to be type specific.

Animals↗
PubMed1996

Papillomavirus-like particles for serology and vaccine development.

Genital infection with high-risk human papillomaviruses (HPV) has been etiologically linked with the development of cervical and other anogenital cancers. There is therefore a need for an effective HPV vaccine with the potential to significantly reduce the burden of more than half a million new cervical cancer cases in women worldwide each year. The L1 major capsid protein of papillomaviruses expressed in eukaryotic cells self-assembles into virus-like particles (VLP). VLP are attractive subunit vaccine candidates since they lack potentially oncogenic papillomavirus DNA and express the conformationally dependent epitopes necessary to induce high-titer neutralizing antibodies. Prophylactic VLP vaccination has achieved a high degree of protection in animal studies. Thus VLP are now considered the immunogen of choice for human vaccine trials to prevent genital HPV infection. VLP of different HPV have been developed to study the serologic relationship between HPV types. VLP-based ELISA are able to detect antibodies in human sera and are now widely used in epidemiologic studies of the natural history of HPV infection and the associated risk of developing neoplasia.

Animals↗
PubMed1996

Lymphoproliferative responses to Borrelia burgdorferi in circumscribed scleroderma.

Humoral immune responses to Borrelia burgdorferi (Bb) have been reported to occur in certain patients with circumscribed scleroderma (CS) (morphoea). Together with the isolation of spirochaetes from CS skin biopsies, this finding was taken to suggest Bb as the aetiological agent of CS. Since there is cellular immunoreactivity to Bb in patients with chronic Lyme borreliosis (LB), Bb-specific lymphocytic responses were tested in patients with CS. For this purpose, peripheral blood mononuclear cells from CS patients and, as controls, from patients with various manifestations of LB, and from healthy volunteers without any evidence of Bb infection, were exposed to Bb organisms for 5 days and then assayed for DNA synthesis. Stimulation indices (SI) > 10 were scored positive. By performing lymphocyte proliferation tests we found: (i) that not only patients with various manifestations of LB but also a considerable percentage of seropositive (five of 13 = 38%) and seronegative (six of 26 = 23%) CS patients exhibit an elevated Bb-induced lymphocyte proliferation; (ii) that the magnitude of the cellular response seen in CS patients is comparable to that encountered in patients with established Bb manifestations; and (iii) that, within a given patient, antibiotic therapy can result in a significant reduction of this response. These results support a causative role of Bb in at least some CS patients. Bb-induced lymphocyte responses were also seen in both seropositive and seronegative erythema chronicum migrans patients. These findings show that the pattern of Bb-specific immune responses is more complex than previously thought, and underscore the importance of lymphocyte function assays in evaluating the diagnosis of potential Bb infection in seronegative patients.

Adolescent↗