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D A Isenberg

Publications and source records attributed to D A Isenberg.

At least 361 records · Page 20Linked to original sources
PubMed1989

Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis.

Autoantigens cross reactive with mycobacteria are implicated in the pathogenesis of adjuvant arthritis in the rat, and there are reports of changes in the immune response to mycobacteria in human rheumatoid arthritis (RA). We have therefore examined the IgM, IgG, and IgA antibody levels to crude mycobacterial antigens and to two recombinant mycobacterial heat shock/stress proteins (65 kD and 71 kD) in sera from patients with RA, systemic lupus erythematosus (SLE), and Crohn's disease, and from healthy controls. IgA binding to the crude mycobacterial antigens was significantly raised in RA sera, though IgG and IgM binding tended to be lower than in controls. Both IgA and IgG binding to the heat shock proteins were significantly raised in the RA sera. Smaller significant rises in both classes were seen in sera from patients with SLE, and in the IgA class only to the 65 kD protein in Crohn's disease. The rises in IgG and IgA antibodies to the 65 kD protein in RA were significantly higher than in the other diseases, however. It is interesting that this protein is the one responsible for adjuvant arthritis in the rat.

Adult↗
PubMed1989

Antinuclear autoantibodies in chronic liver diseases.

Circulating autoantibodies are often observed in liver disorders, especially in those thought to have an autoimmune etiology-such as primary biliary cirrhosis (PBC) and chronic active hepatitis (CAH). The pathophysiologic role of these antibodies, however, remains obscure. The present study was performed to evaluate the incidence and diagnostic value of different antinuclear antibodies in chronic liver diseases, and to assess whether the antibodies are a non-specific expression of the hypergammaglobulinemia observed in these disorders. We measured six different antinuclear and closely related antibodies (against ssDNA, dsDNA, Poly (I), Poly (dT), RNA and cardiolipin) and their IgG, IgA and IgM isotypes in the sera of 86 patients with autoimmune, as well as other chronic liver diseases--namely, PBC, CAH, alcoholic (AC) and cryptogenic cirrhosis (CC). Antibodies against all the various nuclear antigens were detected in all diseases studied. The incidence ranged from 4% (anti-cardiolipin-IgG in CC) to 74% (anti-Poly (dT)-IgM in PBC). Although the antibody profiles differed among the various disease entities, they were not distinct enough to be of any clinical diagnostic value. In alcoholic cirrhosis antibody levels correlated with corresponding immunoglobulin isotype levels (notably IgA), suggesting a non-specific expression of hypergammaglobulinemia. In the other liver diseases such a correlation was lacking, favoring the existence of an underlying specific antigenic stimulation, or some other more specific immune dysfunction.

Adult↗
PubMed1989

Relation between lymphocytotoxic antibodies, anti-DNA antibodies and a common anti-DNA antibody idiotype PR4 in patients with systemic lupus erythematosus, their relatives and spouses.

Forty-two patients with systemic lupus erythematosus (SLE), 65 of their healthy relatives and 20 spouses were studied for the presence of lymphocytotoxic antibodies (LCA), anti-lymphocyte antibodies (ALA), antibodies to DNA and a common idiotype (Id) PR4. Seventy-one per cent of the patients had positive levels of LCA, and in 34% the PR4 Id was detected; normal levels were found in their families. Anti-PR4, an anti-Id, failed to block the lymphocytotoxic activity in those nine patients who both carried the Id and had LCA. This indicates that the Id was not present on LCA. There was no correlation between anti-DNA antibodies and LCA, suggesting that different mechanisms are involved in their expression.

Antibodies, Antinuclear↗
PubMed1988

Galactosylation of IgG associated oligosaccharides: reduction in patients with adult and juvenile onset rheumatoid arthritis and relation to disease activity.

The prevalence of agalactosyl N-linked oligosaccharides on serum IgG was determined for patients with juvenile onset and with adult rheumatoid arthritis. A significant difference in the prevalence of these structures from age matched controls was found in both types of arthritis. In patients with adult onset rheumatoid arthritis, the results showed a strong correlation between the prevalence of IgG-associated agalactosyl oligosaccharides and disease activity. A correlation between disease activity and agalactosyl structures was also seen in a retrospective analysis of serial IgG samples from patients with juvenile onset disease. The finding that childhood onset arthritis and adult rheumatoid arthritis share a defect of glycosylation of serum IgG suggests that there may be a greater similarity between these two varieties of rheumatoid arthritis than has been hitherto considered. The observation that the incidence of agalactosyl oligosaccharides on IgG fluctuates with disease activity provides indirect evidence for a seminal role for this change of glycosylation in the inflammatory process which, in rheumatoid arthritis, is focused on the synovial tissues and results in bone erosions and joint destruction.

Adolescent↗
PubMed1988

Studies of a common idiotype PR4 in autoimmune rheumatic disease.

A new common idiotype, designated PR4, is described. This idiotype was originally identified on a human hybridoma-derived monoclonal antibody from a patient with leprosy, which binds the major Mycobacterium leprae-derived antigen, phenolic glycolipid-1, poly(ADP)-ribose, DNA, and poly(dT). The PR4 idiotype was found in patients with systemic lupus erythematosus (SLE) (70%), rheumatoid arthritis (40%), and Sjögren's syndrome (15%). It was not, however, found in the spouses of the SLE patients or (unlike other lupus idiotypes) in their healthy first-degree relatives. Although no correlation between PR4 idiotype levels and disease activity in SLE was found, a subset of rheumatoid arthritis patients with high levels of the idiotype was identified.

Antibodies, Anti-Idiotypic↗
PubMed1988

Serial studies of the IgG subclass and functional affinity of DNA antibodies in systemic lupus erythematosus.

The functional affinity and IgG subclass of antibodies to ss and dsDNA were measured by ELISA in five serial samples from 41 patients with systemic lupus erythematosus (SLE) who were divided into relatively homogeneous disease subgroups. Anti-dsDNA antibodies were restricted to IgG1 and IgG3 in renal disease and levels increased with disease severity. Functional affinity of IgG1 and IgG3 anti-dsDNA fell in patients with severe renal disease, suggesting that the high affinity antibody population lost from the serum was localizing in the kidneys. IgG2 anti-dsDNA were found in patients with joint and skin disease alone and in the thrombotic/spontaneous abortion subgroup. IgG2 antibody levels did not correlate with disease severity but did correlate with the presence of antibodies to Klebsiella K30 and may have represented a cross-reactive antibody population.

Antibodies, Antinuclear↗
PubMed1988

Anti La(SSB) identifies a distinctive subgroup of systemic lupus erythematosus.

The relevance of antibodies for La(SSB) as a marker of a distinctive systemic lupus erythematosus (SLE) subset was studied in 185 lupus patients. Anti La was detected in 39 (21%) and was accompanied invariably by anti Ro. Clinically, anti La-positive patients were distinguished by a later age of disease onset, and a low frequency of lupus nephritis. In common with other anti Ro-positive patients they showed a high frequency of keratoconjunctivitis sicca. Anti La identified patients with higher titres of anti Ro antibodies and was significantly associated with HLA-DR3. Serological markers such as these are useful for identifying more homogeneous populations of SLE patients for studies of aetiology and pathogenesis.

Adult↗
PubMed1988

Successful treatment of Raynaud's syndrome with Iloprost, a chemically stable prostacyclin analogue.

Twelve female patients with severe secondary Raynaud's phenomenon were treated in a randomized order with both placebo and Iloprost infusions. Infusions were for 5 hours on 3 consecutive days and Iloprost was administered at variable dosage from 1.0 to 3.0 ng/kg/min. A 6-week follow-up period was used between the two sets of infusions. A significant number of patients reported Iloprost had improved Raynaud's symptomatology compared with placebo and this effect lasted for up to 6 weeks. The number of attacks of Raynaud's as recorded by patients in diary books was similarly reduced after Iloprost. Digital and nail-bed blood flows measured by laser-Doppler methods were increased for up to 6 weeks after Iloprost, but not after placebo infusions. Iloprost may be a useful therapeutic agent in the treatment of severe secondary Raynaud's syndrome.

Aged↗
PubMed1988

A comparison of autoantibodies and common DNA antibody idiotypes in SLE patients and their spouses.

In order to determine whether environmental influence per se might influence autoantibody production, sera from the spouses of 20 SLE patients were examined. No antibodies to cardiolipin, poly (ADP-ribose), or ENA were detected and none had detectable rheumatoid factor. One weakly positive ANA reaction was noted, one had anti-DNA antibodies (by RIA and ELISA) and in two sera the common DNA antibody idiotype 16/6 was found. The idiotype was not, however, present on either anti-DNA or anti-K30 antibodies. Although long-term analyses are required, it is evident that sharing the same environment with patients who commonly express a wide range of autoantibodies and common idiotypes rarely leads to their expression in non-autoimmune subjects.

Antibodies, Antinuclear↗
PubMed1988

Effects of the lupus anticoagulant in patients with systemic lupus erythematosus on endothelial cell prostacyclin release and procoagulant activity.

A disturbance in endothelial cell (EC) function may be pathogenetic in the thrombotic tendency of patients with the lupus anticoagulant (LA). The ability of serum from normal subjects and patients with systemic lupus erythematosus (SLE), with and without the LA, to modulate the release of prostacyclin (PGI2) and the expression of procoagulant activity by cultured human EC was investigated. Only the 10% and 20% serum concentrations from patients with SLE-LA produced a significantly greater inhibition of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) release (the stable metabolite of PGI2) than control serum. However, when patients with SLE-LA having Raynaud's phenomenon were excluded from this group, there was then no significant difference between the effect of the patient and control serum. Serum from patients with SLE +/- LA caused a significant increase in EC procoagulant activity compared to healthy controls. The two-stage partial thromboplastin time expressed in seconds decreased from 66 (normal) to 34 (SLE - LA) and 31 (SLE + LA), but there was no significant difference between the patients with and without the LA. The significantly increased EC procoagulant activity induced by serum from patients with SLE +/- LA may account for the observed increased incidence of thrombotic events in patients with SLE. Our data suggest that factors other than decreased prostacyclin release are responsible for the altered hemostasis observed in patients with SLE + LA.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Correlation of the activation of the fourth component of complement (C4) with disease activity in systemic lupus erythematosus.

Levels of C4d, a fragment of C4 generated during activation of the classical complement pathway, were measured in the plasma of 48 patients with systemic lupus erythematosus, 11 with inactive (group 1), 23 with mildly active (group 2), 14 with moderately/severely active disease (group 3), and 30 healthy subjects. Levels of C3d, C4, and C3 were also measured and the C4d/C4 and C3d/C3 ratios calculated. C4d levels correlated with the degree of disease activity, being higher in group 3 than in group 2, in group 2 than in group 1, and in group 1 than in controls. C4d/C4 gave a similar result. Activation indices of the common complement pathway, C3d and C3d/C3, also correlated with disease activity, but in a non-linear relationship, failing to discriminate between patient groups. C4 and C3 showed no correlation with disease activity. These results indicate that indices of C4 activation, C4d and C4d/C4, provide a laboratory measure of disease activity in lupus patients, for whom an objective assessment of the severity of the disease is not readily available.

Adult↗