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Biomedical subjects

D A Isenberg

Publications and source records attributed to D A Isenberg.

At least 163 records · Page 9Linked to original sources
PubMed1998

Erosive arthritis in systemic lupus erythematosus: analysis of a distinct clinical and serological subset.

Erosive arthritis (EA) in systemic lupus erythematosus (SLE) can be debilitating and deforming with uncertain factors for risk, although antibodies to the A2 hnRNP core protein, known as anti-RA33, have been associated with EA. Two hundred patients under long-term follow-up for SLE were evaluated for EA and associated clinical and serological abnormalities. In addition, sera were tested in a masked fashion for anti-RA33 antibodies in a total of 60 patients: 10 with EA and 50 age-, sex- and ethnically matched controls. Ten of 200 (5%) patients with SLE, mainly non-white women, had EA. There were trends for increased renal involvement (P = 0.06), Sjögren's syndrome (P = 0.07) and Raynaud's phenomenon (P = 0.03) in patients with EA compared to those without EA. Rheumatoid factor (RF) was increased in patients with EA (P < 0.02), as were antibodies to double-stranded DNA (P < 0.05), Sm (P < 0.01) and La/SS-B (P < 0.001). Anti-RA33 antibodies were present in 70% with EA compared to 28% without EA (P < 0.05). RF correlated with anti-RA33 antibodies in patients with EA, but not with the presence of anti-RA33 alone. Thus, anti-RA33 antibodies may identify those patients with SLE who are at risk for EA, and an association with RF suggests a common immune response or pathological mechanism in autoimmune erosive joint disease.

Antibodies, Antinuclear↗
PubMed1998

Correlation of 9G4 idiotope with disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: To compare the levels of the 9G4 idiotope (9G4 Id) in systemic lupus erythematosus (SLE) patients with a detailed disease activity index, the British Isles Lupus Assessment Group (BILAG) index, and serological parameters of disease activity by ds DNA antibody levels and serum C3 concentrations. METHODS: In a cross sectional analysis serum samples from 190 patients with SLE were studied and a further 55 serial bleeds from 14 patients. An enzyme linked immunosorbent assay was used to measure the 9G4 Id, and anti dsDNA and antimyeloperoxidase (MPO) antibodies. The C3 levels were measured by laser nephelometer. RESULTS: Seventy six of 190 (40%) of the patients tested had raised 9G4 Id levels. In the cross sectional study 9G4 Id levels were found to correlate with disease activity in the BILAG cardiovascular/respiratory renal, and haematological systems and with global BILAG score (p < 0.01). In the serial bleeds 9G4 Id levels correlated with anti-dsDNA antibody and C3 levels, but not with anti-MPO antibodies. No correlations were found with treatment. In six cases the 9G4 Id levels correlated well with global BILAG scores and dsDNA antibody levels. In four cases the BILAG global and 9G4 Id levels alone correlated well. CONCLUSIONS: Raised levels of the 9G4 Id are present in a substantial proportion of serum samples from patients with lupus, correlate with various aspects of disease activity in SLE. The Id is detectable on anti-dsDNA antibodies, though it must also be present on other immunoglobulins whose specificities remain unknown.

Antibodies, Antinuclear↗
PubMed1998

Naturally occurring anti-idiotypic antibodies reactive with anti-DNA antibodies in systemic lupus erythematosus.

The levels of 'putative' anti-idiotypic antibodies reactive with F(ab')2 fragments of affinity purified DNA binding antibodies from five SLE patients were measured in the serum of active and inactive systemic lupus erythematosus (SLE) patients, their relatives, spouses and healthy non-related individuals. Serum anti-idiotypic antibodies of the IgG isotype could be detected in the serum of 8/15 inactive SLE patients, 3/19 active SLE patients, 17/27 SLE relatives, 1/4 SLE spouses and 6/32 healthy non-related individuals. When the serum immunoglobulins from the individuals in each group were separated into IgG and IgM antibody fractions and analysed, a significant increase in levels of IgG anti-idiotypic reactivity were found in healthy individuals (16/32), whilst no significant increase in IgG anti-idiotypic antibodies were detected in SLE patients, SLE relatives and SLE spouses. Comparatively few individuals tested showed detectable levels of IgM anti-idiotypic antibodies. These results demonstrate that anti-idiotypic antibodies reactive with anti-DNA antibodies are detectable in the serum of SLE patients, SLE relatives, SLE spouses and healthy individuals, and are predominantly of the IgG isotype. The increased frequency of IgG anti-idiotypic antibodies after separation from serum IgM antibodies infers that anti-idiotypic activity of some IgG immunoglobulins in the sera of healthy individuals may be masked by the presence of IgM antibodies in the serum.

Adolescent↗
PubMed1998

Functional disability and end organ damage in patients with systemic lupus erythematosus (SLE), SLE and Sjögren's syndrome (SS), and primary SS.

OBJECTIVE: To determine the accumulated end organ damage and health status in patients with SS and to compare with patients with SLE (with or without SS). METHODS: Thirty-seven patients with primary SS were studied and compared with 120 patients with SLE and 21 patients with SLE and SS. The Medical Outcome Survey Short Form 20 with an additional question for fatigue was used to assess health status. The SLICC/ACR damage index with a supplementary oral section was used to assess end organ damage. For statistical analysis, logistic regression analysis, Fisher's exact test, and Kruskal-Wallis rank tests were applied. RESULTS: Patients in all 3 groups had reduced quality of life with respect to all aspects of functional status and well being. There was no difference between the groups. In the primary SS group, the greatest damage was in the oral section (62% of patients). The patients with SLE and SS had the greatest renal, peripheral vascular, and musculoskeletal damage (24, 19, 38% of patients, respectively) followed by the SLE group. Ocular damage was more common in the primary SS group, but that was due to older age in this group. Malignancy was most common in the primary SS group (11%). Other organ damage scores did not differ between groups. CONCLUSION: End organ damage is uncommon in primary SS (with the exception of oral damage), but the degree of functional ability is as great as in SLE.

Adult↗
PubMed1998

Anti-beta2-glycoprotein I, anti-prothrombin and anticardiolipin antibodies in a longitudinal study of patients with systemic lupus erythematosus and the antiphospholipid syndrome.

OBJECTIVE: To determine anti-beta2 glycoprotein-I (anti-beta2GPI) and anti-prothrombin (anti-ProT) antibody levels, and the IgG subclass distribution of anti-beta2GPI antibodies, in serial samples from patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) having initial or recurrent thrombotic/neurological (T/N) events during the study period. To investigate the correlations between these antibodies and beta2GPI antigen, anticardiolipin antibody (aCL), anti-double-stranded (ds) DNA, C3 levels and disease activity. METHODS: Fifty serum samples were identified from seven patients with SLE who had had T/N events during the follow-up from a cohort under long-term follow-up. IgG anti-beta2GPI, anti-ProT, aCL, IgG subclasses of anti-beta2GPI and beta2GPI antigen levels were determined by ELISA. Corresponding disease activity [British Isles Lupus Assessment Group (BILAG)], anti-dsDNA and C3 levels were compared. RESULTS: IgG anti-beta2GPI antibody levels were elevated in six of the patients before and after the T/N events with less marked fluctuations than aCL antibody levels. The predominant subclass of anti-beta2GPI antibodies was IgG2 before and after the T/N events. IgG anti-ProT antibodies were negative in all cases. There was a significant but weak correlation between anti-beta2GPI and aCL antibodies. No correlation was found between disease activity and IgG anti-beta2GPI antibody and beta2GPI antigen levels. There were fluctuations in beta2GPI antigen levels and a trend to increase after T/N events was observed in some patients. CONCLUSION: Most of the patients with a T/N event during the study period had IgG anti-beta2GPI, but not IgG anti-ProT antibodies. Many IgG aCL-negative samples were found to have IgG anti-beta2GPI activity during the follow-up period. The predominant subclass of IgG anti-beta2GPI was IgG2, which may have importance in the pathogenesis of APS. beta2GPI antigen levels were found to be increased in some patients with SLE after T/N events. IgG anti-beta2GPI antibodies may be used as an adjunctive marker of future T/N events in patients with SLE and APS with aCL antibodies and lupus anticoagulant.

Adult↗
PubMed1997

Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus.

Genetic susceptibility confers significant risk for systemic lupus erythematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involvement of a genetic locus includes linkage, we tested a candidate region homologous to a murine SLE susceptibility region in 52 SLE-affected sibpairs from three ethnic groups. We analyzed seven microsatellite markers from the human chromosome 1q31-q42 region corresponding to the telomeric end of mouse chromosome 1, the region where specific manifestations of murine lupus, including glomerulonephritis and IgG antichromatin, have been mapped. Comparing the mean allele sharing in affected sibpairs of each of these seven markers to their expected values of 0.50, only the five markers located at 1q41-q42 showed evidence for linkage (P = 0.0005-0.08). Serum levels of IgG antichromatin also showed evidence for linkage to two of these five markers (P = 0.04), suggesting that this phenotype is conserved between mice and humans. Compared to the expected random distribution, the trend of increased sharing of haplotypes was observed in affected sibpairs from three ethnic groups (P < 0.01). We concluded that this candidate 1q41-q42 region probably contains a susceptibility gene(s) that confers risk for SLE in multiple ethnic groups.

Adolescent↗
PubMed1997

Interleukin 6 activates heat-shock protein 90 beta gene expression.

The levels of the cytokine interleukin-6 (IL-6) and the heat-shock protein hsp90 have both been reported to be elevated in patients with active systemic lupus erythematosus (SLE). We show that hsp90 protein accumulates to increased levels in both HuH7 hepatoma cells and peripheral blood mononuclear cells (PBMCs) treated with IL-6. In PBMCs this effect occurs without induction of the other hsps, paralleling the specific elevation of hsp90 in SLE. IL-6 is able to activate the hsp90 gene promoter directly; this activation can also be achieved by overexpressing either of the transcription factors NF-IL-6 or NF-IL-6 beta whose synthesis is induced by IL-6 treatment. Hence the induction of hsp90 protein accumulation by IL-6 is likely to be dependent on the enhanced activity of the hsp90 beta gene promoter produced by increased levels of NF-IL-6 and/or NF-IL-6 beta. These effects are discussed in terms of the role of hsp90 in the normal immune system and the mechanism of its activation in patients with SLE.

Blotting, Western↗
PubMed1997

Magnetic resonance imaging of the brain and cerebral proton spectroscopy in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the prevalence and extent of cerebral changes in patients with systemic lupus erythematosus (SLE) by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). METHODS: SLE patients (47 women) and controls (25 women) underwent 1.5T MRI. A semiautomated segmentation technique calculated cerebrospinal fluid (CSF) and brain volumes. Proton MRS of the frontal and parieto-occipital white matter yielded metabolite ratios of N-acetyl groups (NA), choline, and creatine. RESULTS: Compared with the control group, the SLE patients more often had cerebral atrophy on MRI (32% versus 0%), confirmed by an increase in the CSF to intracranial volume ratio. The patients also had old infarcts and hemorrhages (8.5% versus 0%) and more small white matter lesions (23% versus 8% had > 5 such lesions). MRS showed relative reduction of NA peaks. Although no patient was studied when acutely ill, prior neurologic involvement was related to abnormal findings. CONCLUSION: MRI and MRS are helpful in the investigation of cerebral complications of SLE. There are chronic changes which may be ischemic in nature. Their precise cause, consequences, and prevention are current challenges.

Adult↗
PubMed1997

The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus.

OBJECTIVE: To test the reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the assessment of patients with SLE. METHODS: Ten patients with SLE, representing a spectrum of damage and activity, were included. Each patient was examined by 6 of 10 physicians from 5 countries, representing 10 lupus clinics. The SLICC/ACR Damage Index was used to assess accumulated damage, and the SLEDAI was used to assess disease activity. The order of the patients and physicians was randomized according to a Youden square design. RESULTS: The SLICC/ACR Damage Index detected differences among patients (P < 0.001). There was no detectable observer difference (P = 0.933), and there was no order effect (P = 0.261). Similar results were obtained with the SLEDAI. There was concordance in the SLICC/ACR Damage Index among observers, despite a wide spectrum of disease activity detected by the SLEDAI. CONCLUSION: Physicians from different centers are able to assess patients with SLE in a reproducible way, using the SLEDAI to assess disease activity and the SLICC/ACR Damage Index to assess accumulated damage.

Adult↗
PubMed1997

Human immunodeficiency virus infection in systemic lupus erythematosus.

This report describes a female patient with systemic lupus erythematosus (SLE) who was infected with the human immunodeficiency virus (HIV). Using stored serum, the precise timing of HIV seroconversion was determined and the early effects of HIV infection on SLE examined. This infection resulted in clinical improvement and the disappearance of autoantibody production. A literature review of the association between HIV and SLE is provided.

Adult↗
PubMed1997

The production, binding characteristics and sequence analysis of four human IgG monoclonal antiphospholipid antibodies.

Antiphospholid antibodies (APL) have a notable association with recurrent miscarriages, arterial and venous thrombosis and thrombocytopenia. Analysis of the potential pathogenic effects of such human antibodies has been hampered by the considerable difficulty in producing IgG as opposed to IgM monoclonal immunoglobulins. We have developed four human monoclonal IgG APL (LJ1, AH2, DA3 and UK4) by fusing the peripheral blood lymphocytes of three patients with SLE with a mouse human heteromyeloma cell line, CB-F7. These antibodies bind to a variety of anionic phospholipids, two (LJ1 and AH2) bind total histones but none binds to ssDNA or dsDNA. Binding to beta 2 GPI is non-specific. UK4 alone demonstrates lupus anticoagulant activity. All four have lambda light chains, two are IgG1 (AH2 and UK4) and two are IgG3 (LJ1 and DA3). These APL utilize VH genes present in the fetally restricted repertoire and multiple somatic mutations in the CDR suggest an antigen-driven process. In contrast, there is no restriction in V lambda gene usage and only one lambda chain is extensively mutated. Two clonally related hybridomas were isolated from a single patients. This supports the theory that clonal expansion is the mechanism whereby antigen selects high affinity mutations.

Amino Acid Sequence↗
PubMed1997

Splenic involvement in rheumatic diseases.

OBJECTIVES: To assess the major reports of splenic involvement in the rheumatic diseases and to highlight several conditions in which potentially life-threatening splenic complications may occur. METHODS: A search of the Medline database ('SilverPlatter': 1966 to 1997) was conducted for all English-language entries related to the spleen and the major rheumatic diseases. Original articles were reviewed from the bibliographies of these Medline-sourced articles. The major rheumatological textbooks were also reviewed for original references. RESULTS: Patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and polyarteritis nodosa (PAN) are at risk of experiencing spontaneous splenic rupture. Splenomegaly is common in both uncomplicated RA and as a feature of Felty's syndrome, in which the patient may be at risk of splenic abscess formation, again a possible complication of SLE and also PAN. Massive splenomegaly appears to be specific to SLE and may be confused with a malignant process. Abnormal splenic function has been documented in RA, SLE, and Wegener's granulomatosis. The spleen may show areas of infarction in several conditions, notably SLE and Wegener's granulomatosis. Splenic atrophy is not uncommon in SLE and may be associated with functional asplenia and a co-incident risk of potentially fatal infection with capsulated organisms. CONCLUSIONS: Serious and occasionally fatal complications within the spleen occur in many rheumatic diseases. Prompt recognition of these complications is important.

Adult↗
PubMed1997

Clinical features of lupus myositis versus idiopathic myositis: a review of 30 cases.

Myositis is a rare but well-recognized complication of systemic lupus erythematosus (SLE). It is reputed to be milder than primary myositis in terms of morbidity and treatment response. This study compares clinical and laboratory features of idiopathic inflammatory myositis in patients with and without evidence of SLE overlap. We performed a case note review of 30 patients with probable or definite polymyositis/dermatomyositis of whom 11 also had definite or probable SLE. Lupus patients were slightly younger at diagnosis than those with primary disease, and more likely to be female. At presentation, quadriceps strength (expressed as a percentage of expected) was significantly reduced in both the lupus (48.9%; 95% CI 29.0-70.4%) and primary (52.0%; 95% CI 43.6-59.4%) myositis groups, and serum creatine phosphokinase (expressed as a multiple of the upper limit of normal) was significantly elevated (11.2; 95% CI 5.3-29.1 vs 10.7; 95% CI 6.1-17.6). During a mean (S.D.) follow-up period of 7.4 (4.1) yr, both groups tended to follow either a relapsing and remitting, or a chronic persistent course, and when last seen quadriceps muscle strength remained significantly depressed. One of the lupus patients and two of the primary myositis patients died due to direct complications of the disease, and one further death was attributable to a complication of therapy. Our results suggest that lupus myositis is often as severe as primary disease and should be treated with equal vigour.

Adrenal Cortex Hormones↗
PubMed1997

Apoptosis in peripheral lymphocytes in systemic lupus erythematosus: a review.

There is increasing evidence to suggest that abnormalities in apoptosis may play a part in the pathogenesis of systemic lupus erythematosus (SLE). For example, there is now considerable evidence that bel-2 expression is enhanced in a proportion of peripheral T cells, but not in B cells, in SLE patients and correlates with overall disease activity regardless of the activity index employed. Further work is required to establish whether enhanced bel-2 expression by some T cells in SLE patients is related to their activation or intrinsically enhanced by genetic predisposition. Mutations in Fas result in a lymphoproliferative syndrome and may play a role in accelerating autoimmune disease. A report of three children with mutations in Fas has once again focused attention on this regulator of apoptosis. The relationships between inducers and inhibitors of apoptosis may differ in different cell types, and must be elucidated before the implications of observations made in lymphocytes from SLE patients can be fully understood.

Animals↗
PubMed1997

Long-term follow-up of autoantibody profiles in black female lupus patients and clinical comparison with Caucasian and Asian patients.

The aim was to determine whether the autoantibody profile in Black female lupus patients is associated with clinical subsets, fluctuates over time and/or reflects disease activity. A clinical comparison with Caucasian and Asian patients matched for age of onset and disease duration was also undertaken. Up to seven serial bleeds from Black female lupus patients who had been followed up for periods of 3.15 yr were tested for antibodies to Ro/SSA, La SSB. Sm, RNP and ribosomal P using ELISA research assays. Significant differences in both clinical and serological profiles between the ethnic groups were found. Varying aspects of disease activity were linked to anti-DNA (renal, cardiovascular, global score), anti-ribosomal P (musculoskeletal, haematology) and anti-Sm (general) antibodies. There are differences in clinical and serological profiles amongst systemic lupus erythematosus patients of different ethnic origin. However, using the BILAG system, relatively few antibodies were found to reflect disease activity accurately in serial measurements.

Adult↗