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Biomedical subjects

D Isenberg

Publications and source records attributed to D Isenberg.

At least 19 recordsLinked to original sources
PubMed2001

Anti-prothrombin antibodies: assay conditions and clinical associations in the anti-phospholipid syndrome.

Anti-phospholipid antibodies (aPL) are associated with an increased risk of thrombosis and recurrent fetal loss. Antibodies to prothrombin (aPT) have been associated with the anti-phospholipid syndrome (aPS). We assessed variations in aPT assay methodology to optimize an aPT method that was used to screen patients with aPS (n = 66). Detection of aPT using enzyme-linked immunosorbent assay was influenced by the concentration of the capture antigen, the microtitre plate type and the buffer system. The combination of gamma-irradiated plates, a phosphate-buffered saline buffer and coating antigen of 10 microg/ml prothrombin was the most sensitive. Both serum and citrate samples are suitable for the detection of aPT. Under these conditions aPT IgM but not IgG were found to be associated with thrombosis and/or fetal loss.

Abortion, Habitual↗
PubMed2001

Autoantibody profiles in the sera of European patients with myositis.

OBJECTIVE: To determine the prevalence of myositis specific autoantibodies (MSAs) and several myositis associated autoantibodies (MAAs) in a large group of patients with myositis. METHODS: A total of 417 patients with myositis from 11 European countries (198 patients with polymyositis (PM), 181 with dermatomyositis (DM), and 38 with inclusion body myositis (IBM)) were serologically analysed by immunoblot, enzyme linked immunosorbent assay (ELISA) and/or immunoprecipitation. RESULTS: Autoantibodies were found in 232 sera (56%), including 157 samples (38%) which contained MSAs. The most commonly detected MSA was anti-Jo-1 (18%). Other anti-synthetase, anti-Mi-2, and anti-SRP autoantibodies were found in 3%, 14%, and 5% of the sera, respectively. A relatively high number of anti-Mi-2 positive PM sera were found (9% of PM sera). The most commonly detected MAA was anti-Ro52 (25%). Anti-PM/Scl-100, anti-PM/Scl-75, anti-Mas, anti-Ro60, anti-La, and anti-U1 snRNP autoantibodies were present in 6%, 3%, 2%, 4%, 5%, and 6% of the sera, respectively. Remarkable associations were noticed between anti-Ro52 and anti-Jo-1 autoantibodies and, in a few sera, also between anti-Jo-1 and anti-SRP or anti-Mi-2 autoantibodies. CONCLUSIONS: The incidence of most of the tested autoantibody activities in this large group of European patients is in agreement with similar studies of Japanese and American patients. The relatively high number of PM sera with anti-Mi-2 reactivity may be explained by the use of multiple recombinant fragments spanning the complete antigen. Furthermore, our data show that some sera may contain more than one type of MSA and confirm the strong association of anti-Ro52 with anti-Jo-1 reactivity.

Antibody Specificity↗
PubMed2001

Lupus in the family--analysis of a cohort followed from 1978 to 1999.

Familial lupus is recognised but rarely described in mother-daughter case pairs. We describe the prevalence of lupus occurring in the first degree relatives of a cohort of 300 lupus patients under long-term follow-up at a specialised lupus clinic. Three instances of mothers and their daughters who both developed the disease are described in detail to try and ascertain whether there are any particular clinical/serological/genetic factors in common which might explain the phenomenon.

Adult↗
PubMed2000

Inhibition of caspase-3-mediated poly(ADP-ribose) polymerase (PARP) apoptotic cleavage by human PARP autoantibodies and effect on cells undergoing apoptosis.

Autoantibodies directed to nuclear antigens are serological hallmarks of autoimmune rheumatic diseases such as systemic lupus erythematosus. Although much more is known about the molecular identity and functions of targeted self-antigens, with few exceptions, evidence that autoantibodies to these targets have a particular function and contribute directly to the pathological process is lacking. Here we show that human autoantibodies reacting with the zinc fingers of poly(ADP-ribose) polymerase involved in the recognition of damaged DNA totally prevent the cleavage of poly(ADP-ribose) polymerase by caspase-3, a process that normally occurs during early apoptosis. Furthermore, these antibodies, which are frequent in certain autoimmune rheumatic and bowel diseases, affect the characteristic features of apoptosis and increase cell survival ex vivo. This new observation is important, because failure to remove autoimmune or abnormal cells can give rise to prolonged autoimmune stimulation and tumor formation.

Antibody Specificity↗
PubMed2000

Lupus patients with fatigue-is there a link with fibromyalgia syndrome?

OBJECTIVE: To determine whether fibromyalgia syndrome (FMS) was more common in patients with lupus who were complaining of fatigue. METHODS: We interviewed 216 patients attending two lupus clinics, all of whom fulfilled the revised American College of Rheumatology (ACR) criteria for lupus. The patients completed a questionnaire and were examined to determine the presence of fatigue and whether they fulfilled the ACR criteria for FMS. Disease activity was measured using the British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage score. Measurements of erythrocyte sedimentation rate, complement C3, lymphocyte count and DNA titre were also performed. RESULTS: Fifty per cent of our patients complained of fatigue, but only 10% of these patients fulfilled criteria for FMS. FMS did not correlate with any measure of disease activity although patients with FMS had lower mean DNA antibody titres and mean SLICC/ACR damage scores. CONCLUSION: A minority of lupus patients with fatigue fulfil the ACR criteria for FMS. Other possible factors leading to fatigue should be considered.

Adult↗
PubMed2000

Fatigue in primary Sjögren's syndrome: is there a link with the fibromyalgia syndrome?

OBJECTIVE: To determine whether fibromyalgia (FM) is more common in patients with primary Sjögren's syndrome (pSS) who complain of fatigue. The association and prevalence of fatigue and FM was recorded in a group of patients with pSS and a control group of lupus patients, a subset of whom had secondary Sjögren's syndrome (sSS). METHODS: 74 patients with pSS and 216 patients with lupus were assessed with a questionnaire to identify the presence of fatigue and generalised pain. From the lupus group, in a subset of 117 lupus patients (from the Bloomsbury unit) those with sSS were identified. All patients were studied for the presence of FM. RESULTS: 50 of 74 patients with pSS (68%) reported fatigue-a prevalence significantly higher than in the lupus group (108/216 (50%); p<0.0087). Fatigue was present in 7/13 (54%) patients with SLE/sSS. FM was present in 9/74 patients with pSS (12%), compared with 11/216 lupus patients (5%), and in none of the patients with SLE/sSS. None of these values corresponds with previously reported figures of the incidence of FM in pSS. CONCLUSION: The results show that fatigue in patients with pSS and sSS is not due to the coexistence of FM in most cases. A lower incidence in the United Kingdom of FM in patients with pSS was found than has been previously reported.

Adult↗
PubMed2000

Endpoints: consensus recommendations from OMERACT IV. Outcome Measures in Rheumatology.

The goal of the 'Outcome Measures in Rheumatology' (OMERACT) process is to select domains and/or outcome measures for clinical trials in each defined disease category according to truth, discrimination and feasibility. OMERACT IV, held in Cancun, Mexico, April 1998, included the module 'Systemic Lupus Erythematosus (SLE)', designed to define a preliminary core set of outcome domains for randomized controlled trials and longitudinal observational studies (LOS). Although specific measures to be used in clinical trials of SLE have yet to be determined, both randomized controlled trials and longitudinal observation studies groups recommended that outcome be assessed in terms of disease activity and damage in all organ systems involved, as well as by health related quality of life, meaningful to patients, and adverse events. These recommendations were ratified by the majority of participants. In a heterogeneous patient population such as SLE, it is recognized that any individual measure of clinical response may reflect only a portion of what might be termed the 'true outcome'. A responder index could integrate such relatively independent measures of outcome into a single assessment, potentially increasing statistical power and decreasing sample size. Results from randomized controlled trials currently underway assessing these outcome domains are eagerly awaited, and are expected to rapidly advance the field.

Clinical Trials as Topic↗
PubMed1999

IgG anti-endothelial cell autoantibodies from patients with systemic lupus erythematosus or systemic vasculitis stimulate the release of two endothelial cell-derived mediators, which enhance adhesion molecule expression and leukocyte adhesion in an autocrine manner.

OBJECTIVE: To investigate the ability of anti-endothelial cell antibodies (AECA) to modulate endothelial cell function. METHODS: The effects of purified IgG from 11 patients with systemic lupus erythematosus (SLE) and 4 patients with systemic vasculitis on the expression of adhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin) by human umbilical vein endothelial cells and on the adhesion of the human promyelocytic cell line U937 were examined in vitro. RESULTS: IgG from 6 of 8 AECA-positive SLE patients and 3 of 3 AECA-positive systemic vasculitis patients up-regulated adhesion molecule expression and leukocyte adhesion to endothelial cells. The 4 AECA-negative samples had no effect. Transfer experiments demonstrated that at later time points (2-8 hours) after AECA addition, endothelium-derived interleukin-1 (IL-1) accounted for the ability of AECA to increase leukocyte adhesion. However, even within very short times after addition of AECA (<30 minutes), endothelial cells released a distinct transferable mediator with similar effects. CONCLUSION: AECA in patients with SLE or systemic vasculitis may contribute to pathogenesis by increasing leukocyte adhesion to endothelial cells. AECA act by inducing the release of at least two endothelium-derived mediators, one (as-yet-unidentified) rapidly and another (IL-1) more slowly, both of which stimulate endothelial cells in an autocrine manner.

Antibodies, Blocking↗
PubMed1999

Overrepresentation of the Fcgamma receptor type IIA R131/R131 genotype in caucasoid systemic lupus erythematosus patients with autoantibodies to C1q and glomerulonephritis.

OBJECTIVE: To test the hypothesis that there is an association between the Fcgamma receptor type IIA (FcgammaRIIA)-H/R131 polymorphism and autoantibodies to the collagenous region (CLR) of C1q in patients with systemic lupus erythematosus (SLE). METHODS: One hundred ninety-five Caucasoid lupus patients were studied. Anti-C1q(CLR) antibodies in serum were measured by enzyme-linked immunosorbent assay (ELISA) and FcgammaRIIA genotype analysis was performed by polymerase chain reaction. Immunoglobulin subclass of the autoantibodies was measured by ELISA. RESULTS: Fifty-six patients were anti-C1q antibody positive, and Ig subclass analysis indicated a predominance of IgG2 anti-C1q antibodies. Analysis of the SLE population as a whole revealed no significant difference in the allele frequencies of R131 and H131 compared with controls. There was, however, a significantly increased frequency of the R131 allele both in the anti-C1q-positive subgroup of patients (chi2 = 7.66, P<0.01) and in the 71 patients with nephritis (chi2 = 7.76, P< 0.01), compared with controls. CONCLUSION: FcgammaRIIA-R131 constitutes a heritable susceptibility factor for the development of SLE with manifestations in the kidney in Caucasoid patients. The close associations demonstrated between this FcgammaRII variant, antibodies to C1q(CLR), and glomerulonephritis may be due to a failure of clearance of the potentially pathogenic IgG2 autoantibody.

Alleles↗
PubMed1999

Analysis of B-cell epitopes of the Ro/SS-A autoantigen.

Autoantibodies to the Ro and La ribonucleoprotein antigens are found in several rheumatoid diseases. The important epitopes have been studied using synthetic peptides and recombinant antigens to understand how they arise and their implication in disease. Here, we analyse the results of epitope mapping studies of Ro60 and Ro52 autoantigens and focus on the major findings to date.

Animals↗