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Biomedical subjects

D A Isenberg

Publications and source records attributed to D A Isenberg.

At least 343 records · Page 19Linked to original sources
PubMed1990

Analysis of factors affecting human hybridoma production.

Human hybridomas were produced by fusion of the GM 4672 cell line with lymphocytes from the peripheral blood, spleen, and bone marrow of patients with systemic lupus erythematosus. Lymphocytes were also obtained from normal human fetal liver of 12 weeks' gestation. The influence of anatomical source, fusion ratio, pre-stimulation with pokeweed mitogen, HLA match, and disease activity at the time of fusion was studied. Supernatants were screened for immunoglobulin secretion and binding to DNA, cardiolipin, poly(ADP-ribose), and histones by enzyme-linked immunoassay. A total of 28 fusions from 14 donors and 6 fusions with fetal lymphocytes were performed. The spleen was found to be the most efficient source of lymphocytes, with a fusion ratio of 1:1 resulting in a maximum yield of 27 clones/10(7) lymphocytes fused. HLA matching was a factor influencing the outcome with HLA A2 matching being the most important. Pre-stimulation with pokeweed mitogen did not improve the fusion frequency, and fusions using lymphocytes from patients with active disease were only marginally more successful. Over 95% of clones secreted immunoglobulin; autoreactivity was found against DNA, histones, cardiolipin, and poly(ADP-ribose). All hybrids with autoreactivity secreted IgM.

Antibodies, Monoclonal↗
PubMed1990

Association of anti-DNA idiotype markers with clinical and serological manifestations in patients with systemic lupus erythematosus.

Serum levels of 6 anti-DNA antibody idiotypes were measured in 65 consecutive patients with systemic lupus erythematosus (SLE) and 45 healthy subjects. Five of the 6 idiotypes were elevated in SLE sera compared to the normal controls (p less than 0.005). Analysis of the associations of the idiotypes with clinical, hematological, and serological characteristics revealed that significantly decreased serum levels of 3 idiotypes (103.1, 100, and 1305) were associated with nephritis and that one of these idiotypes (103.1) was also associated with discoid rash. An association of lowered levels of 3 idiotype markers (604, 1305, and 1400) was also observed with the presence of lupus anticoagulant and anticardiolipin antibodies. Serial studies in individual patients with SLE nephritis failed to show a close correlation of serum idiotype levels with the degree of proteinuria, creatinine clearance, anti-DNA antibody, or complement values. The association of decreased levels of specific idiotypes with the presence of nephritis, discoid rash, and antiphospholipid antibodies suggests the participation of these antibodies in the pathogenesis of disease.

Adolescent↗
PubMed1990

Characteristics of antineuronal antibodies in systemic lupus erythematosus patients with and without central nervous system involvement: the role of mycobacterial cross-reacting antigens.

Sera of 16 patients with systemic lupus erythematosus (SLE) and active involvement of the CNS were examined for the presence of antibodies to human brain neurons, using indirect immunofluorescence of human brain tissue sections. Thirteen of the 16 patients (81%) had high antineuronal titers, which declined during convalescence, compared with 18 of 105 (17%) SLE patients who had no CNS disease. Competition assays showed that the binding of the antineuronal antibodies was blocked by mycobacterial glycolipids and bovine brain extracts. This finding suggests an additional link between mycobacterial infection and SLE.

Adult↗
PubMed1990

A human fetal monoclonal DNA-binding antibody shares idiotypes with fetal and adult murine monoclonal DNA-binding antibodies.

A human DNA-binding monoclonal antibody was produced by fusing the hepatocytes from a 12-week-old human fetus with the lymphoblastoid cell line GM 4672 using polyethylene glycol. This antibody, designated BEG 2, binds to single-stranded (ss) DNA but also binds to double-stranded (ds) DNA, poly(dT), polyI and poly(ADP-ribose), but not to RNA, cardiolipin or K-30. The binding of BEG 2 to these polynucleotides can be inhibited by incubation with polynucleotides in the fluid phase. A rabbit polyclonal anti-idiotype was raised, and using this reagent it was shown that the BEG 2 idiotype is present in normal human serum (7%), systemic lupus erythematosus (SLE) sera (8%) and rheumatoid arthritis sera (23%). The extent of idiotypic sharing between BEG 2 and murine monoclonal DNA-binding antibodies, in particular monoclonal antibody (mAb) 423 (derived from a 15-day-old fetal MRL/Mp-lpr/lpr mouse) and mAb 402 (derived from an adult MRL/lpr mouse), was also investigated. Using a competition ELISA, it was shown that preincubation of BEG 2 with rabbit anti-423 and rabbit anti-402 inhibits the binding of BEG 2 to DNA, and the binding of 402 to DNA by anti-BEG 2 and anti-423. These data suggest that mAb BEG 2, 423 and 402 share common idiotypes, that autoreactivity is present in early fetal life, and that autoantibodies may be encoded for by germline genes, which have been conserved through evolution.

Animals↗
PubMed1990

SLE: a rheumatological view. Analysis of the clinical features, serology and immunogenetics of 100 SLE patients during long-term follow-up.

Clinical features and immunogenetics were assessed in 100 SLE patients attending a rheumatology clinic for periods ranging from six months to 11 years (mean five years). Five-year survival was 88 per cent. Joint problems (94 per cent), rash (90 per cent) and haematological abnormalities (89 per cent) were the most common clinical features; neuropsychiatric disturbance (45 per cent) and renal disease (29 per cent) were seen less frequently. A range of serological abnormalities was found, including antinuclear antibodies (98 per cent) and antibodies to phospholipids (38 per cent). Anti-Sm antibodies (7 per cent) showed a marked ethnic bias. Tissue typing confirmed the importance of genetic factors by demonstrating significant increases in A1, B8 and DR3 in white Caucasians. The composite phenotype A1,B8,DR3 was present in 35 per cent of white Caucasian patients with SLE. The A1,B8 phenotype was associated with a relative risk of 8.0 and B8,DR3 with a relative risk of 8.32.

Adolescent↗
PubMed1989

The mosaic of autoimmunity.

The term 'autoimmune' is applied to a wide spectrum of diseases, which, although they may differ in pathology, share many factors. In their review, portrayed as a mosaic, Yehuda Shoenfeld and David Isenberg illustrate the complexity of these conditions, outlining the many pieces, genetic, hormonal, immunological and environmental that contribute to auto-immunity, and show how their varying combinations lead to diverse diseases.

Animals↗
PubMed1989

A common anti-DNA antibody idiotype and anti-phospholipid antibodies in sera from patients with schistosomiasis and filariasis with and without nephritis.

The serum concentration of a public idiotype (16/6 ID), originally identified on a human hybridoma-derived monoclonal anti-DNA antibody, was raised in patients with S. mansoni and filariasis with or without nephritis, compared to patients with S. haematobium (in which nephritis does not occur) or idiopathic nephritis not associated with infection. There was no significant difference in 16/6 ID levels between patients with or without renal disease, whether associated with S. mansoni or filarial infection. The 16/6 ID-positive antibodies did not bind to native or denatured DNA, using competitive fluid-phase inhibition studies. Anti-cardiolipin antibody (ACA) concentration was increased in patients with either S. mansoni or filarial infection. In filariasis, both IgG and IgM ACA isotypes were elevated, irrespective of the presence of nephritis. In S. mansoni infection, IgA ACA were limited to patients with renal disease, and IgG ACA isotype to patients without overt nephritis. Both isotypes of anti-cardiolipin antibody correlated with levels of the 16/6 ID in patients with S. mansoni or filariasis. The 16/6 idiotype was therefore a feature of chronic helminthic infection, but was not related to anti-DNA antibody levels or specificity. The occurrence of nephritis as a complication of these infections was not related to the prevalence of the 16/6 idiotype.

Antibodies, Antinuclear↗
PubMed1989

Elevated levels of the 90 kd heat shock protein in a proportion of SLE patients with active disease.

The human 90 kd heat shock protein (hsp 90) is associated with the receptor for glucocorticoid hormones and is believed to play a role in the cellular response to corticosteroids. The levels of this protein in the peripheral blood lymphocytes of patients with systemic lupus erythematosus (SLE) have been investigated and compared with those observed in normal individuals and patients with rheumatoid arthritis. Fifteen percent of SLE patients were found to exhibit hsp 90 levels well in excess of those observed in the other groups. These patients all had active disease. The significance of these findings is discussed both in terms of the disease processes occurring in these patients and the efficacy of steroid therapy.

Adrenal Cortex Hormones↗
PubMed1989

Analysis of autoantibody reactivity and common idiotype PR4 expression of myeloma proteins.

Sera from 75 patients with monoclonal gammopathies and with no clinical evidence of autoimmune disease have been screened for a wide range of autoreactivity including binding to DNA, cardiolipin, extractable nuclear antigen (ENA), rheumatoid factor activity and the presence of the common anti-DNA antibody idiotype PR4. The sera of 17/75 (23%) patients possessed autoreactivity: six were positive for anti-DNA activity, two had anticardiolipin activity and the PR4 ID was found in two sera (both of which possessed anti-DNA activity). Antibodies to ENA were found in one serum (anti-Ro) and anti-organ-specific antibodies in five. Using iso-electric focusing and immunoblotting we have shown that the PR4 ID and DNA binding activity are carried on the paraprotein and not on some other serum constituent. The IgG subclass distribution of 55 IgG paraproteins has also been investigated. The majority of IgG paraproteins belong to IgG1 subclass (55%), with the others, being IgG2 (4%), IgG3 (9%) and IgG4 (27%). In this study we have shown that sera from myeloma patients frequently possess autoreactivity, and that in many cases this can be attributed to the paraprotein.

Antibodies, Antinuclear↗
PubMed1989

Sjögren's syndrome: association with type-1 diabetes mellitus.

This study of 102 unselected type-1 diabetic patients has shown that sicca symptoms affect 55% of the patients, although sometimes only during hyperglycaemic phases. While these symptoms might be attributable to the diabetes, the frequency of antinuclear antibodies in those suspected of having Sjögren's (25% by HEp-2) and particularly anti-Ro antibodies (32% by ELISA) reinforces the suspicion that Sjögren's syndrome may underlie their presence.

Adolescent↗
PubMed1989

Elevated IgG antibody levels to the mycobacterial 65-kDa heat shock protein are characteristic of patients with rheumatoid arthritis.

We have previously demonstrated raised levels of IgG and IgA antibody to the mycobacterial 65-kDa heat shock protein (hsp) in the sera of patients with rheumatoid arthritis (RA). We have now attempted to determine whether this phenomenon is specific for RA, and whether it is seen only with the mycobacterial homologue of this particular hsp gene family. We therefore screened antibody levels to the mycobacterial and Escherichia coli hsp 65, and the mycobacterial, E. coli, and human hsp70, in sera from RA, systemic lupus erythematosus (SLE), tuberculosis (TB), ankylosing spondylitis (AS), Crohn's disease, and control donors. RA sera show the greatest increase in IgA binding to the mycobacterial hsp65, but no increase in IgA binding to the E. coli homologue. Similarly, only RA and TB sera show increased IgG binding to the mycobacterial hsp65, and we have shown previously that the titre is greater in RA. In contrast, the use of mycobacterial and E. coli hsp70 preparations as control bacterial hsp gene products has shown that RA patients do not differ from TB or SLE patients in their antibody binding to these proteins. Moreover, neither IgA nor IgG antibody to the human hsp70 in RA sera were higher than in TB, and the IgA binding was not higher than in SLE. These findings suggest that elevated IgG antibody levels to the mycobacterial hsp65 shows some disease specificity, and further studies with the human homologue and at the T-cell level are required.

Adult↗
PubMed1989

Does rheumatoid factor protect lupus patients from the development of nephritis?

It has been suggested again recently that the presence of rheumatoid factor (RF) in the serum of patients with systemic lupus erythematosus (SLE) protects them from the development of nephritis. In this study the RF is measured by standard latex test and by radioimmunoassay to detect IgM, IgA, and IgG isotypes, in patients with SLE with (26 patients) and without (25 patients) renal involvement, and in a control group of 21 patients with idiopathic renal disease. In addition, patients with SLE and nephritis were tested during active and inactive phases of their disease. No significant protective effect was observed from the presence of RF.

Humans↗
PubMed1989

Serological abnormalities, including common idiotype PR4, in families with rheumatoid arthritis.

A broad range of autoreactivity among a group of 12 French patients with rheumatoid arthritis (RA) and 58 of their healthy first degree relatives has been identified. Over 15% of the patients were found to have antibodies to ssDNA, histone H1, H2A, and H2bB. Among the relatives, IgG and IgM rheumatoid factor and antibodies to ssDNA, H2A, and H4 were present in more than 10%. Even more remarkable, a common anti-DNA antibody idiotype designated PR4, known to be present in 70% of patients with systemic lupus erythematosus (SLE), was found in approximately 30% of both patients with RA and their healthy relatives. This is quite different from its lack of increased expression in relatives of patients with SLE and suggests that in the family members of those with RA a particular combination of environmental influence on germline gene expression is responsible.

Antibodies, Anti-Idiotypic↗