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E Penner

Publications and source records attributed to E Penner.

At least 55 records · Page 3Linked to original sources
PubMed1989

Antinuclear antibodies in patients with chronic idiopathic autoimmune thrombocytopenia followed 2-30 years.

We determined whether serological investigations can assist to distinguish between chronic idiopathic autoimmune thrombocytopenia (cAITP) and immune-mediated thrombocytopenia in patients at risk to develop systemic lupus erythematosus (SLE); 82 patients were seen in this institution for the evaluation of immune thrombocytopenia. In nine of these patients a diagnosis of SLE was made at presentation or shortly thereafter. In the remaining 73 patients with an established diagnosis of cAITP we obtained serum samples at a median disease duration of 7 years; 45 patients were investigated again 2 years later. cAITP patients suffered from their disease for up to 30 years (median 7 years, range 2-30 years) without developing clinical features of SLE. Elevated antinuclear antibodies were found in all patients with a diagnosis of SLE but also in seven patients with established cAITP. All patients who had thrombocytopenia in association with SLE had additional antibodies to anti-nDNA and/or antibodies to soluble cellular antigens. Neither in the initial, nor in the follow-up investigation, such antibodies were discernible in patients with cAITP. We conclude that patients with cAITP do not develop SLE and do not form antibodies to defined cellular antigens, even if suffering from the disease for many years. The ANA titer does not help to differentiate cAITP from thrombocytopenia of SLE. A differentiation, however, between the two diseases is possible by the combined screening for antinuclear antibodies, anti-nDNA, and antibodies to defined soluble cellular antigens.

Adult↗
PubMed1988

Antibodies to nuclear lamins in autoimmune liver disease.

Antibodies to nuclear lamins were detected in sera of patients with autoimmune liver disease. In indirect immunofluorescence tests, these sera revealed staining of the nuclear periphery. Using isolated nuclei, nuclear matrices, nuclear lamina-pore complexes, and chromatographically purified lamins as antigen source, the nuclear lamins A, B, and C were identified as reactive antigens in immunoblotting experiments. The lamins were also identified by 2-D gel electrophoresis. Antibodies to nuclear lamins occurred in 12 of 16 cases of active lupoid hepatitis, but not in 35 patients with the disease in remission. However, only 3 of 37 sera of patients with primary biliary cirrhosis contained anti-lamin antibodies. Autoimmune liver disease sera reacted preferentially with lamins A/C and less frequently with lamin B or lamins A/B/C.

Antibodies↗
PubMed1988

Augmentation of IgE receptor expression and IgE receptor-mediated phagocytosis of rat bone marrow-derived macrophages by murine interferons.

Receptors for IgE (Fc epsilon R) on rat bone marrow-derived macrophages (BMDM phi) were demonstrated by a rosette assay employing trinitrophenyl-coated ox erythrocytes (EoTNP) sensitized with mouse IgE anti-dinitrophenyl monoclonal antibody (EoTNP-IgE). Virtually all BMDM phi emerging from bone marrow cells cultured for 1 week in the presence of mouse L929 cell supernatant, with partially purified murine CSF-1 or recombinant murine GM-CSF, formed IgE rosettes. To study the effect of interferons (IFNs) on Fc epsilon R expression, 1-week-old rat BMDM phi were incubated with murine recombinant IFN-gamma, purified IFN-alpha or IFN-beta, and were tested for their capacity to bind and ingest EoTNP sensitized suboptimally with IgE. A marked increase in the percentage of cells forming IgE rosettes or phagocytosing EoTNP-IgE was noted after 8-72 hr incubation of BMDM phi with 0.1-1000 U/ml of IFNs. At similar concentrations IFN-gamma and IFN-beta triggered EoTNP-IgE binding or ingestion more efficiently than IFN-alpha. The enhancing effect was blocked by the respective anti-IFN antibodies, cycloheximide or actinomycin D but not by mitomycin C. The IgE rosette formation and IgE-mediated phagocytosis were dose-dependently inhibited by native rat IgE but not by heat-denaturated IgE myeloma protein IR162 or monomeric rabbit IgG. Our results demonstrate that rat BMDM phi express constitutively Fc epsilon R, and that murine IFNs augment Fc epsilon R-mediated binding and ingestion in a time- and dose-dependent manner. This effect probably reflects an increase in the number of Fc epsilon R per cell, as a result of de novo synthesis of Fc epsilon R.

Animals↗
PubMed1987

Surface phenotypes of human peripheral blood mononuclear cells from patients with gastrointestinal carcinoma.

Peripheral blood mononuclear cells (PBMC) from 40 patients with gastrointestinal carcinoma (GIC), 13 patients with primary carcinoma in other localizations(non-GIC), and from 57 apparently healthy donors were isolated by Ficoll-Paque gradient centrifugation. The separated cells were stained with several monoclonal antibodies and subjected to analysis on a fluorescence-activated cell sorter. A decreased percentage of PBMC expressing T cell antigens was noted amongst GIC patients, and was mainly due to a reduction of the Leu 2a subset, thus, leading to an increase in the Leu 3a/Leu 2a ratio from 1.4 to 2.1 Non-GIC patients had decreased numbers of both T helper and suppressor cells. Amongst PBMC from GIC and non-GIC patients a statistically increased percentage of cells expressed LeuM 2 (P less than 0.001), LeuM 3 (P less than 0.001), OKM 1 (P less than 0.005), VEP 9 (P less than 0.001), and HLA-DR (P less than 0.001) antigens compared to healthy controls. The percentage of cells bearing these monocyte/macrophage antigens correlated well with the number of cells having monocyte morphology, stained for non-specific esterase, phagocytosed latex particles, and expressed Fc IgG receptor. Our results demonstrate clearly that tumor-bearing patients have an increased relative number of monocytes. The data suggest that cells of the macrophage lineage may be involved in defense mechanisms and changes of the immune system evoked by various tumors.

Adolescent↗
PubMed1987

Nature of immune complexes in autoimmune chronic active hepatitis.

Immune complexes containing antinuclear antibodies have been observed in autoimmune chronic active hepatitis. Using a library of nuclear constituents (deoxyribonucleic acid, small nuclear ribonucleoproteins, and histones), we analyzed the antigens involved in formation of immune complexes. Immune complexes were defined in dissociation experiments, and after separation under dissociating conditions. Immune complexes composed of histones and immunoglobulin G were observed in four of nine immune complex-positive autoimmune chronic active hepatitis sera. Immune complexes containing the small nuclear ribonucleoprotein U1-RNP and immunoglobulin G were observed in two additional samples. Kidney eluates obtained from 2 patients with autoimmune chronic active hepatitis and membranous glomerulonephritis revealed enrichment of anti-U1-RNP, suggesting specific deposition of this antibody in complexed form. Circulating immune complexes containing histones were observed only in patients with autoimmune chronic active hepatitis-associated sicca syndrome; those containing U1-RNP were restricted to patients with autoimmune chronic active hepatitis associated with kidney disease.

Antibodies, Antinuclear↗
PubMed1987

HLA-DR antigens in systemic lupus erythematosus: association with specificity of autoantibody responses to nuclear antigens.

HLA-DR antigens and autoantibodies to the nuclear or cytoplasmic antigens Ro/SSA, La/SSB, Sm, and RNP were determined in North American and Austrian patients with systemic lupus erythematosus (SLE). Analysis of the association of antibodies to these ribonucleic acid (RNA)-protein antigens with HLA-DR antigens showed that HLA-DR3 was related to the presence of anti-Ro/SSA or anti-La/SSB, or both. In contrast, anti-Sm or anti-RNP, or both were associated with HLA-DR4. HLA-DR5 was associated with absence of these autoantibodies. The data extend evidence for the complexity and heterogeneity of SLE. Moreover, they indicate that, in SLE, genes linked to those coding for HLA-DR antigens, are related to the specificity of autoantibody responses rather than to the primary immunological abnormalities of this disorder.

Adolescent↗
PubMed1987

Autoimmune sera recognize a 100 kD nuclear protein antigen (sp-100).

Autoimmune sera from patients suffering from undifferentiated connective tissue diseases (UCTD), Sjögren's syndrome (SS), primary biliary cirrhosis (PBC) and other disorders were found to contain antibodies that produce a distinctive nuclear spot pattern with HEp-2 cells in immunofluorescence studies. These spots which vary in size and number, are spread over the whole nucleus with the exception of the nucleoli. This pattern is easily distinguishable from the staining patterns of anti-centromere, anti-RNP, anti-nucleolar and anti-Scl-70 antibodies. In cells of non-human origin this pattern is discerned only at high serum concentrations. Immunoblotting experiments with a soluble protein fraction from HeLa nuclei revealed that the antigenic target common to all sera is a polypeptide of 100 kD with a pI value of about 5.2. The correlation between immunofluorescence and immunoblotting data was confirmed by affinity-purification of sp-100 specific autoantibodies followed by immunofluorescence experiments.

Aged↗
PubMed1987

High prevalence of antibodies to histones among patients with primary biliary cirrhosis.

Histones are small, basic proteins involved in the packing of DNA into the eucaryotic nucleus. Using an immunodot assay and an enzyme-linked immunosorbent assay (ELISA), sera from patients with liver disease were tested for antibodies to the five individual histones H1, H2A, H2B, H3 and H4. Histones extracted from calf thymus and separated into individual fractions by gel exclusion chromatography were either immobilized on nitrocellulose or adsorbed to microtitre plates and the resulting immune complexes examined via a streptavidin-biotin bridge. Of the liver disease sera tested, only specimens obtained from primary biliary cirrhosis patients contained antibodies reactive with histones. The predominant reactivity was to histone H1 and H2B, and amounted to 74% for IgM antibodies, and 60% for IgG antibodies. Our data indicate that antibodies specific for histones might represent a novel serological marker for primary biliary cirrhosis.

Adult↗
PubMed1986

Scl 70 autoantibodies from scleroderma patients recognize a 95 kDa protein identified as DNA topoisomerase I.

Sera of patients suffering from the autoimmune disease progressive systemic sclerosis (PSS) are known to contain autoantibodies which have been reported to recognize a 70 kDa antigenic protein, designated the Scl 70 antigen. By immunoblotting of nuclear extracts from HeLa cells with sera from scleroderma patients we observed that the size of the antigen present in such cells depends on the conditions of antigen isolation. When protease inhibitors were included in the extraction buffer, a 95 kDa protein was identified instead of a 70 kDa protein. When protease inhibitors were omitted, a number of polypeptides in the size range 66 to 95 kDa was found. Furthermore, antibodies which had been affinity purified on the 95 kDa antigen, crossreacted with the 66 to 95 kDa polypeptides. These results suggest that the smaller proteins were degradation products of the 95 kDa antigen. Immunofluorescence studies on PtK-2 cells with the antibody specific for the 95 kDa protein gave staining of nuclei, nucleoli and of chromosomes and the nucleolar organizer region in mitotic cells. Since this distribution of antigens within the nucleus was reminiscent of the intranuclear distribution of DNA topoisomerase I found by others we probed purified DNA topoisomerase I from calf thymus directly with the autoantibodies from PSS patients, and also the 95 kDa antigens of HeLa cell nuclei with antibodies raised against the bovine DNA topoisomerase I. From the crossreaction pattern observed with the different antigens and antibodies we conclude that DNA topoisomerase I is one of the antigenic components against which autoantibodies are formed in scleroderma patients.

Antigen-Antibody Complex↗
PubMed1986

Demonstration of immune complexes containing the ribonucleoprotein antigen Ro in primary biliary cirrhosis.

We have previously demonstrated circulating and tissue-fixed immune complexes containing the small cytoplasmic ribonucleoprotein antigen Ro and immunoglobulin G (IgG) in a case of sicca syndrome associated with primary biliary cirrhosis. To establish the overall prevalence of such complexes in liver disease, we performed dissociation experiments under conditions of Ro antigen excess. Of the diseases tested, Ro-containing immune complexes were restricted to cases with primary biliary cirrhosis. Sera from 29 of the 47 patients with primary biliary cirrhosis (60%) showed IgG-containing immune complexes; 10 of the 29 sera samples (34%) positive for IgG-containing immune complexes exhibited immune complexes composed of Ro and anti-Ro IgG. These complexes sedimented predominantly as intermediate or large aggregates and were encountered most frequently in cases with extra-hepatic features.

Antigen-Antibody Complex↗
PubMed1986

Nuclear antigens recognized by antibodies present in liver disease sera.

Nuclear and nuclear matrix proteins of HeLa cells were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and subsequently transferred onto nitrocellulose. Antibodies present in sera of patients with primary biliary cirrhosis and autoimmune chronic active hepatitis reacted with some of the blotted proteins. The antibodies were mainly directed against chromatin-associated proteins and protein constituents of discrete RNP particles. In addition, antibodies found in autoimmune liver disease sera detected a hitherto undescribed nuclear protein of 54 kD, and a nuclear matrix protein of approximately 150 kD. Antibodies recognizing a nuclear 25 kD doublet apparently constituted a marker antibody for autoimmune liver disease. Those directed at the 17 kD centromere protein were associated with the primary biliary cirrhosis-related CREST syndrome, while those recognizing La antigen were related to cases of sicca syndrome associated with autoimmune liver diseases.

Antibodies, Antinuclear↗
PubMed1985

[Immune complexes: studies on animal models].

A review is presented of some selected experiments conducted on animal models of immune complex-mediated diseases. The immune response and kinetics of antigen deposition are analysed in the model of systemic chronic serum sickness of rabbits and chickens. Experimental nephritis, induced by mercuric chloride, illustrates a pathogenesis in which autoantibodies to basement membranes become components of immune complexes. A recently developed Streptococcus mutans-induced nephritis in rabbits should make it possible to obtain some understanding of early pathogenetic mechanisms. These could very well be analogous to aspects of the pathogenesis of streptococcus-associated nephritides of man.

Animals↗
PubMed1985

Systemic lupus erythematosus: delineation of subpopulations by clinical, serologic, and T cell subset analysis.

Patients with systemic lupus erythematosus (SLE) (n = 194) were analyzed for correlation of clinical features. In addition, the proportions of the two major T cell subsets were determined in 87 subjects. Two patient subgroups were discerned: one in which severe renal disease, leukopenia, and thrombocytopenia predominated, and a second in which sicca syndrome and involvement of the central nervous system, lungs and muscle occurred. The ratio of T helper/inducer to T suppressor/cytotoxic cells was reduced in the first group and increased in the second. We conclude that SLE does not comprise a single disease entity, but rather represents a number of syndromes with overlapping clinical features. The correlation of clinical symptoms with the proportions of circulating T cell subsets suggests that several immunologic mechanisms may underlie the various types of SLE.

Adult↗
PubMed1985

Scl-86, a marker antigen for diffuse scleroderma.

More than 300 sera from patients with a connective tissue disease were analyzed with the immunoblotting technique. The presence of autoantibodies against an 86,000-mol wt marker antigen for diffuse scleroderma (Scl-86) was found in 14 out of 33 patients with scleroderma. The presence of anti-Scl-86 antibodies seemed to correlate with the diagnosis of diffuse scleroderma since they were found in 13 out of 22 diffuse scleroderma patients and in only one out of 11 patients with limited scleroderma. All scleroderma sera (33 patients' sera and 13 reference sera) were also tested for the presence of anti-Scl-70 antibodies. It was found that all anti-Scl-70 positive sera (n = 25) contained anti-Scl-86 antibody as well, suggesting a relationship between these two antigens. However, the Scl-86 antigen was shown to be an extremely insoluble nonchromosomal protein, resistant to boiling in sodium dodecyl sulfate. This contrasts with the Scl-70 antigen, which has been described as a thermolabile, soluble antigen present in the chromatin fraction. Together, our results are consistent with the idea that Scl-70 is a degradation product of Scl-86. The Scl-86 antigen is present in freshly prepared rabbit thymus, spleen, and liver nuclei as well as in nuclei from various cultured cell lines, but is not detectable in extractable nuclear antigen from rabbit thymus. In a limited retrospective study, the anti-Scl-86 antibodies were found in two sera from patients with Raynaud's phenomenon before the development of diffuse scleroderma. Therefore, it is possible that screening of patients' serum for this antibody might predict the development of diffuse scleroderma.

Animals↗