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D A Isenberg

Publications and source records attributed to D A Isenberg.

At least 415 records · Page 23Linked to original sources
PubMed1985

Detection of cross-reactive anti-DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives.

Two common cross-reacting anti-DNA antibody idiotypes designated 16/6 and 32/15, previously identified in the serum of patients who have systemic lupus erythematosus, were found in 24% and 7%, respectively, of 147 first-degree relatives. These findings imply that high-frequency germ-line genes exist among lupus relatives, as well as patients. These dominant or public anti-DNA antibody idiotypes are not likely to be pathogenic factors, but are probably a genetically associated phenomenon.

Antibodies, Antinuclear↗
PubMed1985

Lupus-like nephritis heralding the definitive manifestation of systemic lupus erythematosus.

Four patients presented with the nephrotic syndrome. The histological appearances on renal biopsy were in three characteristic and in one suggestive of lupus nephritis. These patients did not initially have other clinical features of SLE, but three had a positive ANA and one a raised DNA titre. Remission occurred in two patients, in one spontaneously and in another following corticosteroid therapy, but two developed renal failure. During follow-up all developed elevated DNA binding levels and arthralgia or lymphopenia. The ARA classification criteria for lupus were only fulfilled at this late stage.

Adult↗
PubMed1985

Tetraplegia as a presenting feature of systemic lupus erythematosus complicated by pulmonary hypertension.

A 28-year-old woman presenting with subacute onset of a tetraplegia is described who was shown to have active systemic lupus erythematosus in association with high circulating anticardiolipin binding and lupus anticoagulant activity. The patient later developed severe symptomatic systemic and pulmonary hypertension and required emergency resuscitation. This case provides further support for an association between antiphospholipid antibodies and the clinical features of central nervous system (CNS) involvement and pulmonary hypertension in SLE.

Adult↗
PubMed1985

Detection of cross-reactive anti-DNA antibody idiotypes on renal tissue-bound immunoglobulins from lupus patients.

Cross-reactive anti-DNA antibody idiotypes have been identified on tissue-bound immunoglobulins in a study of renal biopsies from 26 systemic lupus erythematosus (SLE) patients. 12 (46%) biopsies were shown to have one or both the idiotypes tested for by anti-idiotypic reagents. The idiotypes were identified in the glomerular basement membrane, the mesangial cell cytoplasm, and in focal tuft proliferations. In contrast, in none of 24 immunoglobulin-positive disease control biopsies could either idiotype be demonstrated. Blocking studies in two patients indicated that the idiotypes were on anti-DNA antibodies. These findings indicate that some tissue-bound auto-antibodies are derived from related families of high-frequency germ line genes that are expressed in SLE patients. The potential role of anti-idiotypic therapy in SLE is discussed.

Antibodies↗
PubMed1985

Shared idiotypes are expressed on mouse and human anti-DNA autoantibodies.

The expression of common idiotypes on human and mouse anti-DNA monoclonal autoantibodies made by hybridomas was examined by their competitive binding to anti-idiotype antibodies. Some murine autoantibodies inhibited the binding of a human anti-DNA autoantibody 16/6 to monoclonal or polyclonal anti-idiotypic antibodies. Another human antibody (134) was not inhibited in its binding to homologous anti-idiotypic antibodies. The expression of the human 16/6 idiotype on mouse antibodies was restricted to those that had a specificity similar to the 16/6 antibody itself, their major properties being that they reacted more strongly with single stranded DNA (ssDNA) than double stranded DNA (dsDNA). One mouse antibody expressing the 16/6 idiotype also bound weakly to RNA. The results imply structural similarities between the binding sites of the antibodies in the two species, and are consistent with evolutionary conservation of V genes coding for primitive ancestral antibodies that react with DNA and become diversified through somatic mutation.

Animals↗
PubMed1984

Anti-DNA antibody idiotypes in systemic lupus erythematosus.

Monoclonal anti-DNA antibodies prepared by the hybridoma technique were used for an analysis of idiotypes of anti-DNA antibodies in systemic lupus erythematosus (SLE). Serum levels of one idiotypic marker, 16/6/R, were higher than normal in 40 of 74 patients (54%) with active SLE, compared with only 6 of 24 patients (25%) with inactive SLE, 9 of 38 patients (25%) with rheumatoid arthritis, and 4 of 96 normal subjects (4%). Levels of the 16/6/R idiotypic marker were determined in serially collected serum samples from 12 patients with SLE. Concordance was found between idiotype levels and clinical activity in 8 of the 12 patients. Levels of the 16/6/R idiotype tended to correlate with levels of antibodies to double-stranded DNA, but in some cases the clinical status was reflected better by the idiotype levels than by the levels of anti-double-stranded-DNA antibodies. Measurement of idiotypes of anti-DNA antibodies may provide information valuable in monitoring the clinical course of patients with SLE.

Antibodies, Monoclonal↗
PubMed1984

Multiple serologic reactions and their relationship to clinical activity in systemic lupus erythematosus.

Analysis of the binding of serum from 56 systemic lupus erythematosus patients to native DNA (nDNA), denatured DNA (dDNA), poly I, poly(dT), RNA, and cardiolipin revealed multiple antigen binding in many of the sera. Raised levels of antibodies (IgG and/or IgM) to denatured DNA were found in the highest percentage (68%) of patients. A small subset of patients with multiple raised IgM antibodies, renal disease, and vasculitic skin rash was identified. No correlation between multiple serologic activity and clinical disease was found.

Adolescent↗
PubMed1984

Fatal pneumococcal epiglottitis in lupus overlap syndrome.

A 35-year-old woman with a six-year history of polymyositis, having developed a vasculitic skin rash in the first trimester of her first pregnancy and biopsy-proven lupus glomerulonephritis during the third trimester is described. Investigations performed one month post-partum revealed high DNA binding, the presence of RNP antibodies, a serum CH50 of 0% and a serum C2 of 1%. Despite marked clinical and serological improvement and the reduction of her prednisolone dose to 5 mgs./day, she died at one-year post-partum of acute pneumococcal epiglottitis.

Adult↗
PubMed1984

Binding of cytoskeletal proteins by monoclonal anti-DNA lupus autoantibodies.

Monoclonal anti-DNA antibodies produced by hybridomas derived from MRL-lpr/lpr mice and human lupus patients were found to bind to the cytoskeleton of mink lung cells. When tested by indirect immunofluorescence, 17/29 human monoclonal anti-DNA antibodies reacted with the cytoskeleton; 4 of the 29 also produce antinuclear reactions with epithelial cells. The cytoskeletal staining was not inhibited by prior treatment of the cells with DNase, but it was completely blocked by prior incubation of the monoclonal antibodies with DNA and other nucleic acids. The ability of the polynucleotides to inhibit the cytoskeletal staining corresponded to their ability to bind to the antibodies in competitive immunoassays. An (Fab')2 preparation of a monoclonal antibody bound to the cytoskeleton as well as the whole immunoglobulin. The effect of colcemid on the staining pattern, the blocking effect of a monoclonal antivimentin antibody, and results with nitrocellulose blots of cellular proteins indicated that the cytoskeletal protein to which the antibodies bound was vimentin.

Animals↗
PubMed1984

An immunohistological study of secondary Sjögren's syndrome.

The labial biopsies from 13 patients with secondary Sjögren's syndrome (SS) and four disease controls were examined with a panel of monoclonal antibodies to human leucocyte antigens. Large numbers of T cells were found in most of the biopsies. In seven SS patients the T helper/inducer subset was found to be predominant. Antibody to HLA class I antigens consistently stained leucocytes, but other cell types stained more variably. Although the staining with antibody to HLA class II antigen was often weak, approximately as many cells stained with this antibody as with an antileucocyte antibody, implying that the T cells were activated. Anti-IgD revealed membrane staining of a corona of IgD-positive cells in structures resembling germinal centres. Isolated cells throughout the sections also showed strong cytoplasmic staining with anti-IgD. These results suggest a role for T-cell-dependent local antibody synthesis in the pathogenesis of the disease.

Adult↗
PubMed1984

Effect of high-dose methylprednisolone therapy on phagocyte function in systemic lupus erythematosus.

Circulating phagocytes play a major role in the defence of the host against microbial infection. In an attempt to identify the reason for the unusual susceptibility to infection of patients with systemic lupus erythematosus (SLE) various parameters of phagocytic cell function were assessed kinetically in whole blood, and the accumulation of cells in areas of inflammation was studied in vivo with the skin window technique. The effect on these parameters of conventional therapy with glucocorticoids and pulse therapy with large doses of methylprednisolone were examined. Patients on conventional doses of steroids had no abnormality of phagocyte function that might have predisposed to infection, apart from a reduced accumulation of monocytes in areas of inflammation and decreased lactoferrin secretion. Pulse therapy with methylprednisolone considerably delayed the secretion of lactoferrin and the adherence of neutrophils in most of the patients, as well as impairing bacterial killing and digestion.

Adult↗
PubMed1984

Elastase activity in serum and synovial fluid of patients with connective tissue disorders.

Sera and synovial fluids (SF) from patients with connective tissue disorders had significantly lower levels of elastase than sera from healthy controls. Patients with rheumatoid arthritis had significantly lower elastase activity in SF compared with serum. Elastase activity in serial serum samples from patients with systemic lupus erythematosus undergoing plasmapheresis showed some relationship with the clinical condition but little correlation with levels of circulating immune complexes. It was concluded that free elastase in the serum or SF was unlikely to be of much pathological significance in connective tissue disease.

Adult↗
PubMed1983

Idiotypic cross-reactions of monoclonal human lupus autoantibodies.

Idiotypic cross-reactions were evaluated in 60 polynucleotide-binding monoclonal lupus autoantibodies produced by human-human hybridomas that were derived from seven unrelated patients with SLE. Three antiidiotype reagents were prepared by immunization of rabbits or a mouse with monoclonal autoantibodies from two patients. Binding of the three reagents to their corresponding idiotypes was inhibited by one or more polynucleotides, an indication that the antiidiotypes reacted with the variable regions of the autoantibodies. Each antiidiotype appeared to detect a different idiotypic determinant. Of the 60 monoclonal autoantibodies tested, 40 reacted in one or more competitive immunoassays; 15 reacted with one antiidiotype, 10 reacted with two antiidiotypes and 15 reacted with three antiidiotypes. A monoclonal antiidiotype reagent cross-reacted with autoantibodies from six of the seven patients. The idiotypic cross-reactions of immunoglobulins from unrelated patients suggest that the autoantibodies are derived from related families of germ line genes that are expressed by patients with SLE.

Animals↗
PubMed1983

Muscle changes in ankylosing spondylitis.

Muscle biopsy of the quadriceps femoris was carried out in 20 patients with classical ankylosing spondylitis (AS). Histological and histochemical studies revealed changes in all biopsies to a varying degree. Central migration of nuclei was present in 80%, reduced fibre size with some atrophy in 40%, localized reaction to acid phosphatase in 75% and a peripheral condensation of reaction product to NADH-TR stain in 55% of biopsies. Furthermore 14 out of 16 patients, whose quadriceps strength was measured, were found to be below the predicted values, when compared to healthy controls of similar weight, and quantitative surface electromyography in 10 showed lower mean power frequency than in controls. A raised plasma creatine kinase was found in only two patients. It is concluded that muscle changes occur in AS and these may account for some of the clinical features of the disease.

Adult↗