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D A Isenberg

Publications and source records attributed to D A Isenberg.

At least 325 records · Page 18Linked to original sources
PubMed1991

Sequence analysis and idiotypic relationships of BEG-2, a human fetal antibody reactive with DNA.

Monoclonal antibody (mAb) BEG-2 is a dsDNA binding IgM lambda derived from a 12-week human fetus. Two binding site idiotypes (BEG-2 Id alpha and BEG-2 Id beta) have been defined with the use of polyclonal rabbit anti-idiotypic anti-serum. BEG-2 Id alpha is located on the lambda light chain and has been described previously. The BEG-2 Id beta is present on the mu heavy chain. By means of a direct binding ELISA, BEG-2 Id beta has been identified on EBV-derived mAbs from human fetal liver or spleen (5%), human cord blood (2.7%) and adult peripheral blood (1%). In addition, the Id is present on 8.5% of adult spleen-derived hybridoma antibodies and 6% of RA synovium-derived hybridoma antibodies. In all populations the presence of the Id is strongly associated with binding to DNA and other polyanions. Competition assays indicated that the Id was located at or near the antigen-binding site on these molecules. To explore the structural basis of this binding, a major part of the BEG-2 heavy chain was sequenced and found to be encoded by a member of the VH4 family joined to a variant of JH5 by a very short Diversity or N region. Of the BEG-2 Id beta positive mAbs for which the VH family has been determined, five are encoded by VH4 and two are encoded by VH6, but none is encoded by other families. Thus, the BEG-2 Id beta identifies a set of polyreactive antibodies that are common in fetal life, persist into adulthood and are encoded by VH6 and, a subset of VH4 genes.

Amino Acid Sequence↗
PubMed1991

Assessment of common idiotype PR4-Id in serial bleeds from lupus patients.

Marked fluctuations in the levels of a common DNA-antibody idiotype, PR4-Id have been found on IgM and IgA antibodies in particular and to a lesser extent on IgG in serial bleeds of 14 lupus patients. Few clear cut examples were found of the PR4-Id levels reflecting disease activity. However, the idiotype expression was not simply related to total immunoglobulin levels and the controlling mechanisms of idiotype expression on different isotypes remain a matter of conjecture.

Antibodies, Antinuclear↗
PubMed1991

The frequency of a common anti-DNA antibody idiotype (16/6) in different populations of patients with systemic lupus erythematosus.

The 16/6 anti-DNA idiotype (id) is a pathogenic idiotype first identified on a human hybridoma antibody derived from a patient with systemic lupus erythematosus (SLE). The SA-1 anti-DNA, which antibody was established in a similar fashion from a patient with polymyositis, also carries the 16/6 id, although it has a greater reactivity with dsDNA. The presence of the 16/6 id as defined by anti-16/6 and anti-SA-1 was determined in 3 distinct populations of patients with SLE: 502 Mexicans, 98 English (including Caucasians, West Indians, Chinese, Asians) and 93 Israelis. A similar prevalence (around 20%) of the 2 idiotypes was found, with a significant overlap. The latter finding was supported by a significant correlation noted between the prevalence of the 2 idiotypes (r = 0.58 p less than 0.001). Despite the fact that 16/6 antibody is most probably encoded by a germline gene, thus being genetically determined, no distinction in the prevalence of the ids could be detected between completely different populations of patients with SLE. This finding may support the independent pathogenic role ascribed to the 16/6 id.

Antibodies, Antinuclear↗
PubMed1990

Analysis of glycosylation changes in IgG using lectins.

A simple rapid assay based on the ability of lectins to bind carbohydrates has been developed to analyse changes in the oligosaccharide chains of IgG. Bandeiraea simplicifolia lectin and Ricinus communis agglutinin have been used to detect terminal N-acetylglucosamine and galactose moieties respectively in IgG using immunodot-blotting. IgG samples (approximately 1 micrograms) were dot-blotted onto nitrocellulose followed by boiling of the blots to expose the carbohydrate moieties. The blots were then treated with biotinylated lectins followed by either streptavidin-biotin-hydrogen peroxidase conjugate or 125I-labelled streptavidin. The colour was developed using chloronaphthol and the blots read on a densitometer. The labelled blots were cut and read on a gamma counter. The use of a monoclonal antibody to N-acetylglucosamine is also discussed. The results obtained using this method are comparable to those obtained by structural analysis.

Arthritis, Rheumatoid↗
PubMed1990

The relationship between CD5-expressing B lymphocytes and serologic abnormalities in rheumatoid arthritis patients and their relatives.

The influence of genetic factors on the expression of CD5+ B lymphocytes and their relationship to a broad spectrum of autoantibodies was investigated in a study of 12 patients with rheumatoid arthritis (RA) and 52 of their healthy first-degree relatives. The proportion of CD5+ B cells was significantly higher in RA patients (mean +/- SEM 23.9 +/- 2.7%) compared with that in their relatives (18.3 +/- 1.1%, P less than 0.05) and compared with that in a group of healthy control subjects (16.1 +/- 1.8%; P less than 0.05). Much more striking, however, were the high levels of CD5+ B cells found in the patients and their relatives in 5 of the families studied. Increases in total immunoglobulin levels and autoantibody levels were frequently observed in RA patients (approximately 20-40%) and their relatives (approximately 10-20%). Furthermore, a statistically significant correlation (P less than 0.01) between IgM rheumatoid factor and the percentage of B lymphocytes expressing CD5 was observed.

Adult↗
PubMed1990

The antibody repertoire of early human B cells. II: Expression of anti-DNA-related idiotypes.

Cord blood B cells were immortalized in vitro with Epstein-Barr virus (EBV). Supernatants containing greater than 500 ng/ml IgM from clones/lines were tested for expression of anti-DNA-associated 16/6 and PR4 idiotypes (id) by ELISA. Four of 70 lines, but no clones, were positive for 16/6 id and none expressed the PR4 id. The presence of 16/6 id on four cell lines was associated with specificity for ssDNA, cardiolipin and Fc of IgG. No association was seen with binding to the K30 polysaccharide of Klebsiella. One clone binding this antigen also had anti-ssDNA, anti-Fc and anti-cardiolipin activity but did not express 16/6 id. Our data support the germ-line nature of the 16/6 id and are consistent with the notion that IgM autoantibody-producing B cells use VH genes which are part of the normal B cell repertoire.

Antibodies, Antinuclear↗
PubMed1990

Spontaneous antibody-secreting cells against DNA and common environmental antigens in systemic lupus erythematosus.

Cells spontaneously secreting IgG or IgM antibodies to DNA or to common environmental antigens--influenza virus haemagglutinin, adenovirus hexon and mannan from Candida albicans--have been enumerated by ELISA spot in blood from patients with systemic lupus erythematosus (SLE) and normal donors. Mean values were raised for all antigens in the disease, with those for DNA being no greater than for the other antigens. In normal donors, levels of IgM-secreting cells were similar for DNA and the environmental antigens whereas virtually no IgG anti-DNA secreting cells were found. When results were expressed relative to total numbers of IgG or IgM-secreting cells, the differences between the groups disappeared or were greatly reduced in all systems except IgG anti-DNA. These findings are consistent with a requirement for both polyclonal activation and a self-antigen response in the production of IgG autoantibodies in SLE.

Antibodies, Antinuclear↗
PubMed1990

DNA polymorphism of major histocompatibility complex class II and class III genes in systemic lupus erythematosus.

We investigated the Taq I digested DNA restriction fragment length polymorphism (RFLP) of the Major Histocompatibility Complex (MHC) class II genes: HLA-DRB, -DQA, and the class III genes: C4 and 21-hydroxylase(CYP21) in 56 caucasoid patients with systemic lupus erythematosus (SLE) and 62 control subjects in order to define the molecular variation of these genes and their association with SLE. The results showed that the gene frequencies of both HLA-DR2 and -DR3 were significantly increased in the SLE population compared to normal subjects (DR2: 21.4% vs 10.7% chi 2 = 4.5. DR3: 29.6% vs 13.3%; chi 2 = 8.3). A high frequency of C4A and CYP21A gene deletions was also found in SLE patients (SLE 52%, normals 24%). All of 22 SLE patients, and 12 of 15 normal subjects who had C4A and CYP21A gene deletions had a 10.0kb Taq 1 DRB RFLP attributable to the presence of HLA-DR3. Family studies showed linkage of C4A/CYP21A deletions with HLA-B8 and -DR3, and confirmed the previously demonstrated association of the HLA-B8, DR3, C4A*Q0, C4*B1, Bf*S, C2*C haplotype with SLE. Deletions affecting the C4A and CYP21A genes were the commonest cause of C4A null alleles in SLE. No strong association between C4 null phenotype or C4 gene deletion, as determined by RFLP, was observed in patients who possessed DR2.

Complement C4↗
PubMed1990

Detection of enterovirus specific RNA sequences in muscle biopsy specimens from patients with adult onset myositis.

A subgenomic cDNA probe with broad specificity for a range of enteroviruses was used to test by an in situ hybridisation technique for the presence of enterovirus specific genomic sequences in muscle biopsy samples obtained from patients with chronic adult myositis. Virus specific RNA sequences were detected in 6/13 (46%) patients with idiopathic polymyositis or dermatomyositis. Control samples obtained from an equal number of patients suffering from other muscle disorders were negative. A monoclonal antibody specific for an enterovirus group was used to probe for viral antigens by indirect immunoperoxidase staining; all biopsy samples from test and control groups were negative.

Adult↗
PubMed1990

Correlation between clinical features of systemic lupus erythematosus and levels of antihistone antibodies of the IgG, IgA, and IgM isotypes.

An attempt was made to define the correlation between the clinical features of systemic lupus erythematosus and levels of circulating antihistone antibodies of the IgG, IgA, and IgM isotypes. Serum antibody levels were determined by enzyme linked immunosorbent assay (ELISA) on serial blood samples (n = 4) from 25 patients, representing five subgroups: (a) renal disease; (b) central nervous system disorders; (c) skin and joint disease only; (d) serositis; and (e) deep venous thrombosis with or without spontaneous abortion. The levels of antihistone antibodies of each isotype varied widely from patient to patient, but antibody levels in the four samples from each patient correlated closely. A close correlation between levels of IgG and IgA antihistone antibodies was found but there was no correlation between these isotypes and IgM antihistone antibodies. In individual patients no simple correlation between disease activity and antihistone antibody levels was established, but levels of antihistone antibodies of the IgG and IgA isotypes were significantly higher in those patients in whom the disease was consistently more active.

Autoantibodies↗
PubMed1990

Assessment of the effect of oral corticosteroids on bone mineral density in systemic lupus erythematosus: a preliminary study with dual energy x ray absorptiometry.

Dual energy x ray absorptiometry and a wide range of blood and urine tests were used to assess the propensity of patients with systemic lupus erythematosus to develop an impairment of bone mineral density. Surprisingly, in this preliminary study no significant differences in bone mineral density were found when patients taking 10 mg or more of prednisolone for six months or longer were compared with those who had never taken prednisolone.

Administration, Oral↗
PubMed1990

Disease specificity of antibodies to poly (ADP-ribose); their relationships to anti-DNA antibodies and to disease activity in lupus.

In this study we have measured the level of anti poly (ADP-ribose) antibodies in the sera of a number of patients with SLE and their relatives, patients with a wide variety of other autoimmune and infectious diseases, and a group of normal healthy controls. It was found that these antibodies were not disease specific but were present in nine out of thirteen groups tested in significant numbers. The levels of anti poly (ADP-ribose) antibodies and anti DNA antibodies in SLE patients bled serially were also measured. The level of these antibodies fluctuated in parallel in many of these patients, although the anti poly (ADP-ribose) antibodies reflected disease activity more accurately in some.

Antibodies, Antinuclear↗