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D A Isenberg

Publications and source records attributed to D A Isenberg.

At least 397 records · Page 22Linked to original sources
PubMed1987

Measurement of anti-DNA antibodies: a reappraisal using five different methods.

One hundred and thirty coded sera, 60 from patients with systemic lupus erythematosus (SLE) and 70 from patients with other autoimmune rheumatic diseases were tested for deoxyribonucleic acid (DNA) binding activity by five different types of assay. These were enzyme linked immunosorbent assay (ELISA) (distinguishing IgG and IgM anti-ssDNA and anti-dsDNA), Crithidia luciliae, a nitrocellulose filter assay, the Amersham kit, and another modified Farr assay, the radioimmunoassay (RIA) (UK). The Crithidia test was the most specific, none of the controls was positive, but the least sensitive (13% positive only). The RIA (UK) was the most sensitive (57% positive). In most of the assays 3-9% of the controls were positive. When the SLE sera were analysed according to disease activity the IgG anti-dsDNA ELISA, all three RIA values, and the Crithidia test values were raised in all the patients with severely active disease. Some patients with inactive disease, however, were positive in each of the tests. The best interassay correlations (r less than 0.49) were found between RIA (UK), and ss IgG and the Amersham kit; and between ds IgG and ss IgG. In the main, however, it was clear that different assays are dependent upon distinctive properties of DNA antibodies. It seems inevitable that most major rheumatology units will require more than one anti-DNA antibody assay.

Adolescent↗
PubMed1987

HLA class I and II, interferon, interleukin 2, and the interleukin 2 receptor expression on labial biopsy specimens from patients with Sjögren's syndrome.

Labial biopsy specimens from eight patients with primary Sjögren's syndrome (SS), 10 patients with secondary SS, and three healthy controls were studied with monoclonal antibodies identifying HLA class I and class II antigens; interferon-alpha, beta, and gamma; interleukin 2 (IL2); and the IL2 receptor (Tac) among others. In the normal biopsy specimens there was evidence of HLA class I and, to a lesser extent, class II antigens in both ducts and acini, though this was much less marked than in the Sjögren's biopsy specimens. Interferon-gamma staining, but not interferon-alpha or beta, was also considerably enhanced in the biopsy specimens from the patients with Sjögren's syndrome. These data support the view that in Sjögren's syndrome the release of interferon-gamma may be involved in the induction of class II determinants. Our observations were broadly similar in both primary and secondary Sjögren's syndrome except that patients with primary Sjögren's syndrome tended to have more diffusely scattered T lymphocytes.

Aged↗
PubMed1987

Defective degradation of bacterial DNA by phagocytes from patients with systemic and discoid lupus erythematosus.

The digestion of bacterial DNA by peripheral blood monocytes was impaired both in patients with systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE). The monocytes of these patients had both a small quantitative defect in the solubilization of DNA and a marked qualitative defect in the extent to which this DNA was degraded. In addition, neutrophils from patients with SLE released significantly less high molecular-weight DNA than control cells. Digestion of bacterial RNA and protein by phagocytes was not defective in either disease. The reduced digestion of DNA by phagocytes resulted in concomitantly larger amounts of high molecular-weight DNA remaining in these cells. Such sequestration of DNA may contribute to the persistence of fairly large DNA fragments in the tissue of patients with lupus erythematosus.

Adult↗
PubMed1987

The sera of patients with Klebsiella infections contain a common anti-DNA idiotype (16/6) Id and anti-polynucleotide activity.

In view of recent reports linking Klebsiella pneumoniae with autoimmunity, we have examined the sera of 52 patients with urinary tract infection or septicaemia from this Gram-negative pathogen, for the presence of antibodies to DNA, polynucleotides, cardiolipin and a common anti-DNA idiotype 16/6. Up to 27% of these patients had anti-polynucleotide antibodies detectable, and in 37% the 16/6 idiotype was found. Absorption of the sera of two patients, with no DNA binding, against the Klebsiella polysaccharide K-30 induced a significant fall in both their anti-K30 antibody and 16/6 idiotype levels. Among 52 patients with other Gram negative infections a maximum of 17% and 19% respectively, had anti-DNA antibodies and the 16/6 idiotype present in their serum. In 37 normal controls, the rate of antibody and idiotype detection was 5% or less. The presence of autoantibodies in the serum of patients with Klebsiella infections may be the result of non-specific stimulation due to bacterial polyclonal activation. However, there might also be a specific stimulus triggered by idiotypic cross-reaction between autoantibodies and anti-Klebsiella antibodies.

Adult↗
PubMed1987

Profile of autoantibodies in the serum of patients with tuberculosis, klebsiella and other gram-negative infections.

Autoantibody profiles were examined in the sera of untreated patients with tuberculosis, and those with klebsiella septicaemia, and klebsiella and E. coli urinary tract infections. Rheumatoid factors of the IgM, IgA and IgG isotypes, antinuclear antibodies and antibodies to poly(ADP-ribose) were all frequently detected (generally 15-40%). In contrast, antibodies to the extractable nuclear antigens and to the organ specific antigens were unusual (generally less than 10%). In comparison, in a group of lupus patients IgM rheumatoid factor, anti-nuclear antibodies, antibodies to poly(ADP-ribose) and antibodies to the extractable nuclear antigens were more frequently found, but IgA and IgG rheumatoid factors and antibodies to the organ-specific antigens were present in much the same frequency.

Antibodies, Antinuclear↗
PubMed1987

Placental type isoferritins in chronic liver diseases.

Serum ferritin levels in chronic liver diseases were measured by an enzyme-linked immunosorbent assay (ELISA) using two monoclonal antibodies (McAb) against placental ferritin. One of the McAbs (CM-H9) recognizes a specific placental-like isoferritin (PLF) only, while the other McAb (CM-G8) recognizes an isoform (CF) common to human placenta, liver and spleen. The different diseases studied were primary biliary cirrhosis (PBC-14 patients), chronic active hepatitis (CAH-12 patients), alcoholic cirrhosis (AC-18 patients) and cryptogenic cirrhosis (CRY-26 patients). Increased levels of both isoferritine were found in all these liver disorders, with an overall incidence of 80% for CF and 40% for PLF. The mean level of CF was significantly above normal in PBC, AC and CRY and that of PLF in PBC and CRY. Circulating placental-type isoferritins have not been previously described in patients with liver disorders. Our findings indicate that elevation of serum ferritin in liver diseases is caused by different isoferritin components.

Antibodies, Monoclonal↗
PubMed1987

Antibody affinity and IgG subclass of responses to tetanus toxoid in patients with rheumatoid arthritis and systemic lupus erythematosus.

Significant differences in both the affinity and IgG subclass of antibodies produced after immunization with tetanus toxoid have been demonstrated in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) compared to healthy controls. Patients with RA failed to show affinity maturation although they produced similar amounts of antibody to the controls. Some patients with SLE produced very high affinity antibodies although there was a wide spectrum of response. Antibodies to tetanus toxoid in controls were predominantly IgG1 and IgG4 but in RA and SLE there was either a restricted IgG1 response or a more general response in all the IgG subclasses. It is likely that these differences in response reflect the underlying disorders in immunoregulation present in patients with these diseases.

Adult↗
PubMed1986

Preferential secretion of a common anti-DNA idiotype (16/6 Id) and anti-polynucleotide antibodies by normal mononuclear cells following stimulation with Klebsiella pneumoniae.

Peripheral blood mononuclear cells derived from 6 normal subjects were incubated with 5 polyclonal activators (pokeweed mitogen, Epstein-Barr virus, group-A Streptococcus, Staphylococcus aureus and Klebsiella pneumoniae. After 7 days of incubation, the supernatants were examined for immunoglobulin (IgG and IgM) production, the level of a common anti-DNA idiotype (16/6 Id) and autoantibody activity against ssDNA, dsDNA, poly(I), poly(dT) and cardiolipin. Significantly increased levels of the 16/6 Id were recorded only with the Klebsiella stimulated MNC. Increased immunoglobulin levels and autoantibody reactivity were noted with all 5 polyclonal activators. The Klebsiella cell membrane preparation induced the highest values. No correlation was found between the 16/6 levels, autoantibody activity and the absolute concentrations of IgG or IgM. This study, together with previous reports, suggests a role for Klebsiella in the etiology of autoimmune diseases. We suggest that Klebsiella can induce anti-DNA-like autoantibodies not only by polyclonal activation, but also by a more specific stimulus.

Autoantibodies↗
PubMed1986

Haematological reassessment of rheumatoid arthritis using an automated method.

Thirteen haematological parameters were measured in 44 patients with rheumatoid arthritis (RA) and 39 disease control patients with ankylosing spondylitis (AS). Using a 10 000 cells per sample automated differential counter the most frequent abnormalities found were monocytopenia, low numbers of large unstained cells, basophilia and increased numbers of cells with high peroxidase activity (HPX). The total white cell count, lymphocyte and monocyte counts, the HPX count, platelet distribution width and erythrocyte sedimentation rate were able to distinguish RA from AS at a statistically significant level. Discriminant function analysis showed that a maximum of 55% of RA patients could be correctly classified into disease state when combinations of six out of seven laboratory tests were used.

Arthritis, Rheumatoid↗
PubMed1986

Preliminary evidence for gut involvement in the pathogenesis of rheumatoid arthritis?

111Indium leucocyte scans were performed on 26 patients with active rheumatoid arthritis. An abnormal localization of radioactivity was observed in the gut of 12 of these patients, generally in the region of the terminal ileum, caecum and ascending colon. No difference was found in the intake of nonsteroidal anti-inflammatory drugs between those with positive and negative scans. Two patients with positive scans were on no medication. These observations suggest the possibility of a primary role for a gastrointestinal lesion in the aetiology of rheumatoid arthritis, although these abnormalities could be secondary or unrelated.

Adult↗
PubMed1986

Rapid development of cerebral atrophy in systemic lupus erythematosus.

A 21-year-old female is described who developed severe cerebral lupus 9 months after the onset of her disease. A dramatic change in her CT brain scan from normal to gross cerebral atrophy was observed in the month following onset of her cerebral disease. This patient developed hepatitis during the course of her hospitalization. This is an unusual manifestation of systemic lupus. The patient's serum also contained anti-Sm antibodies. This is a relatively infrequent finding in the serum of lupus patients outside the United States.

Adult↗
PubMed1986

The relationship of anti-DNA antibody idiotypes and anti-cardiolipin antibodies to disease activity in systemic lupus erythematosus.

The detection of anti-cardiolipin antibodies and anti-DNA antibody idiotypes has shown utility in a prospective assessment of 42 lupus patients over a 1-year study period. However, so broad is the range of clinical and serological features included in the diagnostic category of SLE that even a combination of tests will often inadequately reflect disease activity at a given time. For the foreseeable future the value of laboratory investigations will probably lie in supporting clinical judgment of the nature of a patient's illness and the severity of the target organ's dysfunction.

Adolescent↗
PubMed1986

A study of anti-poly (ADP-ribose) antibodies and an anti-DNA antibody idiotype and other immunological abnormalities in lupus family members.

The genetic background of systemic lupus erythematosus (SLE) has been reexamined in a study of the serum of 31 lupus patients and 80 asymptomatic first degree relatives by measuring a common, cross reacting anti-DNA antibody idiotype designated 134, antibodies to poly(ADP-ribose), serum C3, circulating immune complexes, and antinuclear antibodies (ANA). Over 30% of the relatives had raised 134 and anti-poly(ADP-ribose) levels, and 9% had ANA titres greater than 1/20. In contrast, only one relative had a low serum C3 level. These results confirm that immunogenetic abnormalities associated with the production of autoantibodies and particular idiotypes must exist amongst lupus relatives as well as the patients. The production of autoantibodies, however, is not necessarily matched to the clinical expression of SLE.

Adolescent↗
PubMed1986

High levels of a common anti-DNA idiotype (16/6), a genetic marker for SLE.

Six out of 8 healthy first-degree relatives of a patient with systemic lupus erythematosus (SLE) had very high serum levels of a common anti-DNA idiotype (16/6). In this family an additional sister developed SLE, and all members were heterozygous for C4 deficiency. Measurements of common autoantibody idiotypes may contribute to the understanding of the genetics of autoimmune diseases. They might be found useful in detecting healthy subjects prone to the development of an overt clinical state.

Autoantibodies↗
PubMed1986

Localization of interferons and interleukin 2 in polymyositis and muscular dystrophy.

Muscle biopsies from nine patients with polymyositis, six with muscular dystrophy, six with other muscle diseases and three controls have been studied with a panel of 10 monoclonal antibodies (MoAb) identifying T lymphocytes, HLA-class I antigens, alpha, beta and gamma interferons and interleukin 2 (IL-2). The result confirm that the staining of the sarcolemma with anti-HLA class I antibody is weak or negative, except in areas adjacent to infiltrating leucocytes or where muscle fibre damage is evident. The very similar tissue distribution of alpha, beta and gamma interferons in the polymyositis biopsies supports the hypothesis that interferons are released by the inflammatory infiltrate and induce the class I antigen expression. In contrast, little interferon was demonstrated in the dystrophic muscle implying that class I expression in these disorders must occur by a different mechanism. Little IL-2 was demonstrated in any of the biopsies though some unexplained small dense accumulations were identified by one of the anti IL-2 MoAb.

Adult↗