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D A Isenberg

Publications and source records attributed to D A Isenberg.

At least 109 records · Page 6Linked to original sources
PubMed2000

Human monoclonal anti-phospholipid antibodies selectively bind to membrane phospholipid and beta2-glycoprotein I (beta2-GPI) on apoptotic cells.

The ability of an anti-phospholipid (LJ1) and an anti-beta2-GPI (RSP-57) human MoAb to bind to apoptotic but not viable cells was demonstrated in this study. Both MoAbs were derived from patients with systemic lupus erythematosus and anti-phospholipid antibody syndrome. The parallel analysis of the specificity and affinity of four anti-phospholipid human MoAbs suggests that the binding of LJ1 MoAb to apoptotic cells is a specific property of this MoAb. RSP-57 MoAb recognizes apoptotic cells through beta2-GPI which becomes available for binding after the interaction with negatively charged phospholipids. This observation provides evidence that the binding of human anti-phospholipid antibodies to apoptotic cells occurs in both a beta2-GPI-dependent and independent way and involves a restricted group of epitopes. The finding that LJ1 and RSP-57 MoAbs bind apoptotic cells underlines the property of these MoAbs to act as cell membrane markers of apoptosis. Major pathological implications derive from the observation that LJ1 and RSP-57 MoAbs recognize epitopes expressed on 'early' apoptotic cells. The interference with the in vivo clearance and processing of apoptotic cells is a potential pathogenic mechanism of these antibodies.

Animals↗
PubMed2000

Identification of candidate endothelial cell autoantigens in systemic lupus erythematosus using a molecular cloning strategy: a role for ribosomal P protein P0 as an endothelial cell autoantigen.

OBJECTIVE: To attempt to characterize the diversity and nature of antigens recognized by anti-endothelial cell antibodies (AECA) in patients with systemic lupus erythematosus (SLE) using a molecular cloning strategy. METHODS: AECA in sera of 15 SLE patients were measured by ELISA and Western blot analysis was used to examine the diversity of autoantigen targets in two clinically active patients. A human umbilical vein endothelial cell cDNA expression library was immunoscreened with sera from these two patients to identify their autoantigen targets. An anti-ribosomal P peptide antibody ELISA was used to assess the clinical significance of anti-ribosomal P protein antibodies in the sera of one patient. RESULTS: Significantly higher AECA levels were found in five patients with active disease and nephritis than in five patients with clinically inactive disease. Sera from two clinically active patients were found to recognize distinct spectra of autoantigens. The candidate autoantigens that were identified included (1) endothelial cell-specific plasminogen activator inhibitor; (2) the classical lupus antigen, i.e. ribosomal P protein P0; and (3) proteins never before described as putative autoantigens in SLE, including ribosomal protein L6, elongation factor 1alpha, adenyl cyclase-associated protein, DNA replication licensing factor, profilin II and the novel proteins HEAPLA 1 and HEAPLA 2 (human endothelial associated putative lupus autoantigens 1 and 2). In one patient, antibodies against ribosomal P protein P0 were predominant and levels of these antibodies correlated with total AECA levels, anti-DNA antibody titres, overall clinical score and renal disease in a longitudinal study. CONCLUSIONS: A panel of candidate endothelial autoantigens in SLE, which includes previously described autoantigens and novel targets, has been identified by a molecular cloning strategy. This novel molecular approach could also be applied to the identification of autoantigens in other autoimmune vascular diseases.

Autoantibodies↗
PubMed2000

Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long-term review.

OBJECTIVE: To estimate the risk of malignancy in a UK cohort of patients with systemic lupus erythematosus (SLE) under long-term review. METHOD: The University College London Lupus Clinic Database was used to identify a cohort of 276 patients followed up prospectively between 1978 and 1999. Standardized incidence ratios and 95% confidence intervals for all cancers were calculated using age and sex-specific cancer incidence rates for the southeast of England. RESULTS: In total, 16 malignancies were diagnosed in 15 patients. However, five malignancies were diagnosed before the diagnosis of SLE and were therefore excluded from the final statistical analysis. One case of basal cell carcinoma was also identified, but this was also excluded from the final analysis as no comparable figures were available for the general population. Death as a direct consequence of the malignancy occurred in six (2.3%) patients, accounting for 22.6% of the deaths in our cohort of SLE patients. Compared with the general population, the overall estimated risk for all cancers was not increased in the lupus cohort (standardized incidence rate 1.16 (95% confidence interval 0.55-2. 13). Hodgkin's lymphoma was the only individual cancer that was increased in our cohort of patients [standardized incidence rate 17. 82 (95% confidence interval 0.45-99.23)]. CONCLUSIONS: In our cohort of patients with SLE we did not show an overall increased risk of malignancy. However, SLE was associated with an increased risk of Hodgkin's lymphoma compared with the general population. From our cohort of 276 patients, none of those treated with cyclosporin (3%) developed malignancy, and out of 49 (18%) patients treated with cyclophosphamide only one patient developed malignancy. Out of the 10 patients in the final analysis who developed malignancy, six had treatment with prednisolone, four with azathioprine, five with hydroxychloroquine and only one with cyclophosphamide. No statistical difference in the above cytotoxic therapy was observed between those patients who developed malignancy and those who did not.

Adult↗
PubMed2000

Mucosa-associated lymphoid tissue lymphomas in two patients with rheumatoid arthritis on second-line agents, and secondary Sjögren's syndrome.

We report two patients with rheumatoid arthritis and secondary Sjögren's syndrome whose disease was complicated by a mucosa-associated lymphoid tissue (MALT) lymphoma. Although this particular type of lymphoma is associated with primary Sjögren's syndrome, it has not been described, to our knowledge, in the context of rheumatoid arthritis and Sjögren's syndrome. The potential causative factors are discussed.

Adult↗
PubMed2000

The prevalence of antibodies to anionic phospholipids in patients with the primary antiphospholipid syndrome, systemic lupus erythematosus and their relatives and spouses.

OBJECTIVES: Antiphospholipid antibodies (aPL) have been associated with syndromes involving thrombosis, fetal loss and thrombocytopenia. Genetic and environmental conditions are among the factors attributed to the cause of autoimmune diseases such as the antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The aim of this study was to determine whether these factors determine the prevalence of aPL. METHODS: Three groups of patients were tested for the presence of IgG, IgM and IgA anticardiolipin (aCL), antiphosphatidylinositol (aPI), antiphosphatidylglycerol (aPG) and antiphosphatidylserine (aPS) antibodies: (i) patients with primary APS (PAPS); (ii) patients with SLE and secondary APS; and (iii) patients with SLE without APS. First-degree relatives and spouses of patients with SLE/APS were also tested for circulating aPL. RESULTS: IgG aPL were particularly prevalent in patients with PAPS. IgG aPI and aCL were more prevalent in patients with PAPS than the IgM equivalents (P < 0.0001). Notably, none of the patients with PAPS had IgA aPL. A significantly higher number of relatives of patients with SLE/APS possessed IgG aPL than the normal controls. Except for aPG (P < 0.03), the prevalence of these antibodies in the relatives was not significantly different from patients with SLE/APS. The relatives also had significantly higher prevalence of IgG aPI, aPS and aCL antibodies than IgM aPL antibodies. In contrast, the prevalence of IgG aPL in the spouses was no different than in the healthy controls. CONCLUSIONS: Genetic factors, shared by patients and their relatives, seem to have some effect on the prevalence of aPL in the subjects studied, while environmental factors shared by spouses appear to have no influence.

Adult↗
PubMed2000

Do present damage and health perception in patients with systemic lupus erythematosus predict extent of future damage?: a prospective study.

OBJECTIVE: To study whether either initial damage, disease activity, disease duration, age, a drug score, or health status would predict an increase in damage in patients with systemic lupus erythematosus (SLE) within the next three years. METHODS: A three year prospective longitudinal study of a cohort of 141 consecutive patients with SLE attending a specialist lupus outpatient clinic from their first assessment between July 1994 and February 1995. Disease activity was assessed using the BILAG system, health status by the Medical Outcome Survey Short Form 20 with an extra question about fatigue (SF-20+), and damage by the SLICC/ACR Damage Index (SDI). Damage was reassessed three years later. Statistical analysis was carried out using logistic regression analysis (logXact). RESULTS: 133 female and 8 male patients with SLE (97 white subjects, 16 Afro-Caribbeans, 22 Asians, and 6 others) were included. Their mean (SD) age at inclusion was 41.1 (12.5) years and their disease duration 10.2 (6. 3) years. The mean measures at inclusion were: total BILAG 5.2 (range 0-17), total SDI 1.2 (0-7), drug score 1.2 (0-3); SF-20+: physical 58 (0-100), role 54 (0-100), social functioning 71 (0-100), mental health 64 (16-100), health perception 44 (0-100), pain 53 (0-100), fatigue 59 (0-100). Four patients were lost to follow up because they had moved. At three years in 33 patients the total SDI had increased to a mean of 1.5 (0-7) (n=130). Moreover, seven patients had the maximum damage as they had died during the follow up period. The only variables with an independent and significant contribution in predicting damage at three years were the total damage score (odds ratio (OR)=1.46; 95% CI 1.04 to 2.05), and health perception (OR=0.96; 95% CI 0.93 to 0.99) at inclusion. CONCLUSIONS: Of all the variables at inclusion only the total damage score and SF-20+: health perception, significantly predicted an increase in damage, for patients with SLE, three years later.

Adult↗
PubMed2000

Development of additional autoimmune diseases in a population of patients with systemic lupus erythematosus.

OBJECTIVE: In view of the recognised clustering of autoimmune diseases (AID), the chronology of development of other autoimmune diseases in systemic lupus erythematosus (SLE) patients was considered. METHODS: A retrospective review of a well documented population of 215 patients with SLE was undertaken. The duration of follow up ranged from 2 to 18 years. RESULTS: Of these 215 patients, 65 (30%) had at least one other AID-including 51 (24%) having one other AID, 12 (6%) having two and two (1%) having three other AID in addition to their SLE. Twelve different autoimmune diseases were identified. The majority of patients developed a further AID after SLE had been diagnosed (62%) reflecting the relatively early age of onset of SLE. There was no significant difference in the age of onset of rheumatoid arthritis, Sjögren's syndrome and hypothyroidism that had developed before SLE compared with those who developed these diseases after SLE. However, those who developed autoimmune thrombocytopenia (AITP) before SLE were significantly younger than those who developed AITP after SLE (16.7 v. 38.7 years respectively, p<0.05). CONCLUSIONS: Physicians caring for SLE patients should remain alert to the possible development of a second AID during follow up. Further well matched case-control studies are required to define the exact relation between SLE and other AID.

Adolescent↗
PubMed2000

Risk factors for avascular necrosis of bone in patients with systemic lupus erythematosus: is there a role for antiphospholipid antibodies?

BACKGROUND: Avascular necrosis of bone (AVN) is a well known complication in patients with systemic lupus erythematosus (SLE). OBJECTIVE: To investigate the role of antiphospholipid antibody status (IgM and IgG anticardiolipin antibodies and lupus anticoagulant) with adjustment for corticosteroid use as risk factors for the development of AVN. METHODS: A cohort of 265 patients receiving long term follow up in our SLE clinic from 1978 to 1998 was analysed. Patients with AVN complications were detected and then matched for age, sex, ethnicity, duration of disease, and organ disease with two other patients with SLE. A further 31 patients were chosen at random for the analysis. RESULTS: Eleven patients had AVN, giving a point prevalence of 4%. There were no significant differences demonstrable in the presence of individual antiphospholipid antibodies (aPL) or their combination between the group with AVN or the two control groups. CONCLUSION: Incorporating an adjustment for corticosteroid use we were unable to show a link between the presence of aPL and the development of AVN in patients with SLE.

Adolescent↗
PubMed2000

From BILAG to BLIPS--disease activity assessment in lupus past, present and future.

During the past 16 years, members of the British Isles Lupus Assessment Group (BILAG) have met on a regular basis and have been instrumental in devising a comprehensive disease activity index and, in association with others in the international rheumatological community, devising and/or testing damage and patients self-assessment indices. The history of what the BILAG group has achieved is set out here and the latest attempts at computerisation and improvements in the Disease Activity Index itself are described.

Disease Progression↗
PubMed2000

The variation in anti-ENA characteristics between different ethnic populations with systemic lupus erythematosus over a 10-year period.

OBJECTIVE: To assess how anti-ENA characteristics change in patients with systemic lupus erythematosus from different ethnic backgrounds over a 10-year period follow-up study. RESULTS: There were 61 patients, of whom 37 were Caucasian, 12 were Asian and 12 were Afro-Caribbean. At the first available bleed 12/37 (32%) Caucasians were anti-ENA positive compared to 6/12 (50%) Asians and 9/12 (75%) of Afro-Caribbeans (Chi-squared P=0.01 for Caucasian vs Afro-Caribbean) and these proportions remained essentially unchanged after 10 y of follow-up. However, over the 10 y of follow-up anti-ENA patterns did change, with anti-Ro being the commonest antibody pattern to emerge and anti-Ro/La the commonest antibody pattern to disappear. There were 20/37(54%) Caucasians, 1/12(8%) Afro-Caribbeans and 5/12(42%) Asians who remained negative for anti-ENA throughout the 10-year follow-up (Chi-squared P=0.03 for Caucasian vs Afro-Caribbean). CONCLUSION: Anti-ENA were more commonly found in the Afro-Caribbean than the Caucasian population. The commonest patterns of anti-ENA differ between ethnic groups and, over a 10-year period, anti-ENA patterns in individual patients changed in a significant number of individuals. However, Caucasians were more likely to remain anti-ENA negative over 10 y of follow-up than Afro-Caribbeans.

Adult↗
PubMed2000

How to supervise a thesis: best practice.

Adequate supervision of a research thesis is no simple matter. In this article, the requirements of both the supervisor and the student are considered, and essential recommendations are outlined.

Academic Dissertations as Topic↗
PubMed2000

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for Systemic Lupus Erythematosus International Comparison.

OBJECTIVE: To compare patients with systemic lupus erythematosus (SLE) from different centers with respect to demographics and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and to assess whether the SLICC/ACR DI changed over time, and whether initial DI scores were related to outcome. METHODS: Members of SLICC completed DI scores and patient demographics on patients followed in their centers. Information was provided at 2, 5-10, and > 10 years of followup. Data were entered on computer and analyzed on SPSS/PC+ and SAS using descriptive statistics and analysis of variance. RESULTS: Information for 1297 patients within 2 years of first clinic visit was submitted from 8 centers. There were 1187 women and 110 men with a mean age at diagnosis of SLE of 32 years. Seven hundred sixty-two were Caucasian, 423 were black, and the remainder were of other races. There were more blacks in the American centers than in Canadian or European centers. Five centers provided information for the 3 time periods. The DI increased over time. Ninety-nine patients had died. Higher SLICC/ACR DI scores were documented in patients who went on to die. CONCLUSION: The SLICC/ACR DI is a valid measure for damage in SLE.

American Medical Association↗