Search PubMed⌕ Search

Biomedical subjects

D Isenberg

Publications and source records attributed to D Isenberg.

At least 19 recordsLinked to original sources
PubMed2007

Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study.

OBJECTIVE: To describe the prevalence, characteristics, attribution, and clinical significance of neuropsychiatric (NP) events in an international inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were enrolled within 15 months of fulfilling the American College of Rheumatology (ACR) SLE classification criteria. All NP events within a predefined enrollment window were identified using the ACR case definitions of 19 NP syndromes. Decision rules were derived to determine the proportion of NP disease attributable to SLE. Clinical significance was determined using the Short Form 36 (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). RESULTS: A total of 572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14 years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total, there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion of NP events attributed to SLE varied from 19% to 38% using alternate attribution models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of attribution, had lower scores on the SF-36 and higher SDI scores compared with patients with no NP events. CONCLUSION: Twenty-eight percent of SLE patients experienced at least 1 NP event around the time of diagnosis of SLE, of which only a minority were attributed to SLE. Regardless of attribution, the occurrence of NP events was associated with reduced quality of life and increased organ damage.

Adult↗
PubMed2006

An assessment of renal failure in an SLE cohort with special reference to ethnicity, over a 25-year period.

OBJECTIVES: Although the prognosis for patients with renal lupus has improved, a small number still progress to renal failure. Studies from the USA have found it difficult to distinguish whether the higher rate of renal failure in African-Americans is due to genetic or socio-economic factors. Our aim was to identify ethnic and other factors in a UK lupus cohort that contribute to renal failure. METHODS: The University College London (UCL) Hospitals lupus cohort of 401 patients (Whites 64%, Blacks 19%), followed since 1978, has 127 patients with renal disease, of whom 21 have gone into renal failure. We determined the characteristics and possible causes of renal failure in this group. Black patients were disproportionately represented in the renal failure group (62% vs 19% for Whites). RESULTS: Those in the renal failure group had persistently low C3 compared with the renal disease cohort. A high proportion of patients in the renal failure group were felt to be non-adherent to treatment. CONCLUSIONS: Given that health-care for patients in the UK is free at the point of delivery, we postulate that in our cohort genetic factors rather than socio-economic status are likely to be more significant in causing renal failure. However, there may be cultural and other reasons for this, which requires further study.

Adolescent↗
PubMed2006

Mortality in systemic lupus erythematosus.

OBJECTIVE: To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. METHODS: Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. RESULTS: The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration <1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. CONCLUSION: Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.

Adolescent↗
PubMed2005

An international cohort study of cancer in systemic lupus erythematosus.

OBJECTIVE: There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. METHODS: We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. RESULTS: The 9,547 patients from 23 centers were observed for a total of 76,948 patient-years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05-1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13-3.49), and for non-Hodgkin's lymphoma, it was 3.64 (95% CI 2.63-4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05-1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78). CONCLUSION: These results support the notion of an association between SLE and cancer and more precisely define the risk of non-Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.

Adult↗
PubMed2005

Anti-B cell therapy (rituximab) in the treatment of autoimmune diseases.

The use of B cell depletion as a mode of treatment for non-Hodgkin's lymphoma was first utilized in 1997 when Rituximab, a chimeric human-mouse monoclonal antibody which has a high affinity to the CD20 antigen expressed on B cells, became available. Over 500000 lymphoma patients have been treated worldwide with this drug and it has a good safety record. The notion that B cells might be critical to the development of rheumatoid arthritis led to the extension of the use of B cell depletion to this condition and a recent double blind controlled trial has shown very encouraging results. In addition, B cell depletion either using Rituximab alone, or in combination with cyclophosphamide and corticosteroids has also been reported to have been of great benefit in some patients with severe systemic lupus erythematosus albeit in open label studies. This review considers the mechanism of action of the drug, the clinical trials that have been reported, and tries to place its current use in patients with autoimmune rheumatic disease in context.

Antibodies, Monoclonal↗
PubMed2004

Hepatic manifestations of autoimmune rheumatic diseases.

Hepatic manifestations in autoimmune disease include chronic active hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, and nodular regenerative hyperplasia. These diseases are rare and may occur concomitantly or serially. Clinicians must be aware of the possibility of liver disease so that it can be treated as soon as possible.

Arthritis, Rheumatoid↗
PubMed2004

Specific antinuclear antibodies are associated with clinical features in systemic lupus erythematosus.

OBJECTIVES: To study associations between antinuclear antibodies (ANA) and signs/symptoms in patients with systemic lupus erythematosus (SLE). METHODS: A consecutive cohort of 289 patients with SLE was included; 235 fulfilled ACR criteria for SLE and were further analysed. ANA profiles were determined by line immunoassay and by indirect immunofluorescence on Crithidia luciliae. An extensive list of signs/symptoms was evaluated. RESULTS: Five clusters of antibodies were defined by cluster analysis: 1-antibodies to SmB, SmD, RNP-A, RNP-C, and RNP-70k; 2-antibodies to Ro52, Ro60, and SSB; 3, 4, and 5-antibodies to ribosomal P, histones and dsDNA, respectively. Significant associations (p< or =0.01) were found between anti-RNP-70k, anti-RNP-A, anti-RNP-C and Raynaud's phenomenon, between anti-RNP-A, anti-RNP-70k and leucopenia, and between anti-RNP-A, anti-RNP-C and a lower prevalence of urine cellular casts. Anti-SSA, anti-SSB were associated with xerostomia, and anti-SSB with pericarditis. Antibodies to ribosomal P were associated with haemolytic anaemia, leucopenia, and alopecia. Patients with anti-dsDNA antibodies had a higher risk for cellular casts and a lower risk for photosensitivity. Antihistone antibodies were associated with arthritis. CONCLUSIONS: In a large and consecutive cohort of patients with SLE, clusters of antibodies were identified. Previously reported associations of antibodies with symptoms were confirmed and new associations found.

Adolescent↗
PubMed2004

Does B cell depletion have a role to play in the treatment of systemic lupus erythematosus?

B cell dysfunction and pathogenic autoantibody formation are thought to be critical in the pathogenesis of systemic lupus erythematosus (SLE). In this review we will summarize the results of attempts to utilize B cell depletion, based on the use of a chimeric monoclonal antibody (MAb) specific for human CD20, rituximab, for the treatment of patients with SLE.

Antibodies, Monoclonal↗
PubMed2004

Anti-dsDNA antibodies: still a useful criterion for patients with systemic lupus erythematosus?

The presence of antibodies to dsDNA has been a criterion for systemic lupus erythematosus (SLE) in each of three attempts to classify the disease that have been undertaken by the American College of Rheumatology. The generally good specificity of the test, the fact that it is widely available and often undertaken by an enzyme linked immunosorbent assay (ELISA) which is relatively cheap and easy to perform have encouraged its continued presence in the list of lupus criteria. The detection of anti-dsDNA antibodies is not, however, straightforward and the real significance of the presence of these antibodies, their true specificity (or otherwise), the question of whether they are truly linked to disease pathogenicity and how accurately they reflect disease activity are all questions that have been posed in the past 20 years.

Antibodies, Antinuclear↗
PubMed2003

Studies of human polyclonal and monoclonal antibodies binding to lupus autoantigens and cross-reactive antigens.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease serologically characterized by production of a variety of autoantibodies. Antibodies to double-stranded (ds) DNA are considered to be a diagnostic marker in SLE and their presence often correlates with active disease. The murine R4A anti-dsDNA antibody was found to cross-react with a peptide, D/EWD/EYS/G (R4A peptide), identified by analysing decapeptides selected from a peptide library. The R4A peptide inhibited binding of antibody to dsDNA and antibody deposition in kidneys in vivo. In other previous work, mice immunized with the peptide in a decapeptide form bound to a polylysine backbone, multiple antigenic peptide, were found to develop both anti-DNA and anticardiolipin antibodies. METHODS: To determine if human anti-DNA antibodies bind R4A peptide, we investigated the binding of monoclonal and polyclonal anti-dsDNA and anticardiolipin antibodies to the R4A peptide from patients with SLE. RESULTS: DNA binding by four immunoglobulin (Ig) G and two IgM human monoclonal anti-DNA antibodies was inhibited by the R4A peptide. While monomeric peptide was unable to inhibit affinity-purified polyclonal anti-DNA antibodies, serum anti-DNA reactivity was inhibited by an octameric form of the peptide in 10 SLE patients. CONCLUSIONS: Human anti-DNA reactivity includes the same fine specificity as that present in murine anti-DNA reactivity. Peptide binding might be a useful surrogate marker for SLE.

Adult↗
PubMed2002

Biological treatments for systemic lupus erythematosus.

There have been many recent advances in therapeutic approaches to systemic lupus erythematosus (SLE). The roles of cyclophosphamide, hydroxychloroquine, methotrexate and hormonal treatments in the management of SLE have been investigated in recent randomised controlled trials (1). However, although these pharmacological agents have a role to play in some patients with lupus, broad based effects have led to problems with side effects and adverse reactions. For this reason, more specific therapies are urgently required. Such strategies currently under evaluation include altering the cytokine balance, reducing T cell activation and inducing tolerance, blocking T cell costimulatory molecules, reducing auto-antibody production from B cells, targetting specific genes and stem cell transplantation. These are known as "biological" treatments as their aim is to alter patho-physiological processes occurring in the diseased state. This review will focus on the biological therapies currently under investigation-with particular attention on the cytokine-directed therapies.

Biological Products↗
PubMed2002

Lupus and malignancy.

Explore the source record for details and available documents.

Clinical Trials as Topic↗