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D Isenberg

Publications and source records attributed to D Isenberg.

At least 37 records · Page 2Linked to original sources
PubMed1999

Outcome measures to be used in clinical trials in systemic lupus erythematosus.

The optimal outcome measures to be employed in clinical trials of systemic lupus erythematosus (SLE) have yet to be determined. Useful instruments should assess disease outcome in terms of all organ system involvement, as well as measures important to the patient. This article reviews those outcome measures that have been utilized in cohort studies in SLE, as well as their limited use in randomized clinical trials (RCT). Six disease activity measures have been developed: British Isles Lupus Assessment Group Scale (BILAG), European Consensus Lupus Activity Measure (ECLAM), Lupus Activity Index (LAI), National Institutes of Health SLE Index Score (SIS), Systemic Lupus Activity Measure (SLAM), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). They have been validated in cohort studies as reflecting change in disease activity, and against each other. RCT utilizing SLAM, SLEDAI, BILAG, ECLAM, SIS, SLAM, SLEDAI are ongoing. It is recommended that the disease activity index of choice be selected; but simultaneous computer generation of multiple indices will facilitate comparisons across therapeutic interventions. A damage index has been developed and validated as the Systemic Lupus International Cooperating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index or SDI. In several cohort studies it has been shown sensitive to change over time, and to reflect cumulative disease activity. There is no health status or disability instrument specific to SLE. The Medical Outcomes Survey (SF-20) captures health status/health related quality of life (HRQOL) better than the Health Assessment Questionnaire (HAQ) in patients with SLE, but does not adequately reflect fatigue. The SF-36 does assess fatigue, and correlates closely with the SF-20. These data indicate that any individual measure of clinical response to a therapeutic intervention in SLE may reflect only a portion of what might be termed the "true outcome." Based on this work, the way is now paved to attempt to develop consensus on the important domains to be measured in clinical trials in SLE, the most appropriate instruments to use and the minimal clinically important differences in their results.

Clinical Trials as Topic↗
PubMed1998

Structural basis of the gp120 superantigen-binding site on human immunoglobulins.

B cell superantigens (SAg) interact with normal human nonimmune Igs (Igs), independently of the light chain isotype, and activate a large proportion of the B cell repertoire. Recently, the major envelope protein of HIV-1, gp120, was found to exhibit SAg-like properties for B cells with potential pathologic consequences for the infected host. This unconventional mode of interaction contrasts with its binding to immunization-induced Abs, which requires the tertiary structure of the heavy and light chain variable regions. In this report, we have examined the structural basis of the interaction between human Igs and gp120. We found that gp120 binding is restricted to Igs from the V(H)3 gene family and that the two V(H) genes 3-23 and 3-30, known to be overutilized during all stages of B cell development, frequently impart gp120 binding. We also provide evidence that the viral gp120 SAg can interact with only a subset of the human V(H)3+ Igs that can convey binding to the prototypic bacterial B cell SAg protein A from Staphylococcus aureus. Finally, we have identified amino acid positions present primarily in the first and third framework regions of the Ig heavy chain variable region, outside the conventional hypervariable loops, which correlate with gp120 binding. In a three-dimensional sequence-homology model, these residues partially overlap with the predicted SAg protein A binding site for V(H)3+ Igs.

Amino Acid Sequence↗
PubMed1998

Assessing lupus.

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Humans↗
PubMed1998

Apoptosis and antiphospholipid antibodies.

OBJECTIVE: To analyze the potential links between antiphospholipid antibodies (aPL) and apoptosis in the pathogenesis of the antiphospholipid antibody syndrome (APS). METHODS: A review was undertaken of the most relevant scientific literature on apoptosis and autoimmune phenomena. Experimental and human pathology were reviewed to substantiate the hypothesis that apoptosis is involved in the generation of aPL. RESULTS: Several considerations suggest that exposure of phospholipids (PL) during apoptosis may be a driving antigenic stimulus to the production of aPL. Furthermore, the molecular PL-protein complexes formed during apoptosis are targeted by "pathogenic" aPL. The binding and the clearance of apoptotic cells by these autoantibodies likely further enhances the aPL immune response. Experimental models and human pathology suggest that a restricted genetic background is key to the development of this immune response. CONCLUSIONS: Abnormalities of apoptosis observed in the course of autoimmune conditions likely provide an antigenic stimulus to the production of aPL.

Antibodies, Antiphospholipid↗
PubMed1998

Predictors of lymphoma development in primary Sjögren's syndrome.

OBJECTIVE: To determine the clinical and laboratory predictors of lymphoma development in primary Sjögren's syndrome (pSS). METHODS: Seventy-two patients with pSS were studied. Demographic data, clinical features, serum gamma-globulin levels, autoantibodies, and HLA status were reviewed. For statistical analysis, Mann-Whitney U-test, Fisher's exact test, logistic regression analysis, Kaplan-Meier method, and log-rank tests were applied. RESULTS: Five patients developed a distinct non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT). A history of swollen salivary glands, lymphadenopathy, and leg ulcers predicted lymphoma development. CONCLUSION: Patients with pSS are at increased risk of lymphoma development, and those who have the above risk factors must be carefully observed.

Adult↗
PubMed1997

Correlation between anti-Proteus antibodies and isolation rates of P. mirabilis in rheumatoid arthritis.

In a survey of 89 RA patients, carried out under code, Proteus mirabilis was isolated from the urine of 63% (47/75) of female (P < 0.001) and 50% (7/14) of male patients (P < 0.001), compared to a frequency of isolation in healthy women of 32% (38/119) and 11% (13/115) in healthy men. There was no significant difference in isolation rates between 37 non-RA patients and healthy controls. Sera from 20 patients with RA and 20 healthy controls were tested against P. mirabilis and Escherichia coli by an enzyme-linked immunosorbent assay. Antibodies against P. mirabilis but not to E. coli were significantly higher in the RA patients than in healthy controls (P < 0.001). Furthermore, a positive correlation was found between high anti-Proteus antibody levels in serum samples and the number of Proteus colony-forming units obtained from urine specimens of the 20 RA patients (r = +0.714, P < 0.001). These results support the suggestion of an aetiopathogenic role for P. mirabilis in RA.

Adult↗
PubMed1996

The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus.

OBJECTIVE: To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE). METHODS: A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status. RESULTS: Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients. CONCLUSION: This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.

Health Status Indicators↗
PubMed1996

Autoantibody repertoire to Ro/SSA and La/SSB antigens in patients with primary and secondary Sjögren's syndrome.

Autoimmune diseases are characterized serologically by the presence of antibodies to specific autoantigens. Antibodies to the two antigens Ro/SSA and La/SSB are found in patients with primary (pSS) and secondary Sjögren's syndrome (sSS). To explore if differences in the fine specificity of these autoantibodies could be distinguished in sera from patients with primary (n = 17) and secondary (n = 20) Sjögren's syndrome, sera were analysed by immunoblotting and ELISA using recombinant antigens and synthetic peptides. Minor differences were detected when the frequencies of the Ro 60 kD, Ro 52 kD and La autoantibody specificities to full-length proteins in the pSS and sSS groups were compared. However, when reactivity to different parts of the Ro 60 kD antigen was analysed, including recombinant fragments encompassing amino acid (aa) 1-134, aa 181-320 and aa 397-525, only two sera, both from pSS patients, reacted to the aminoterminal fragment aa 1-134, and 3/4 sera that reacted with the carboxyterminal aa 397-525 fragment derived from sSS patients. Of all the anti-Ro 60 kD positive sera, 80% reacted with the middle fragment encompassing aa residues 181-320. The fine specificity of the autoantibodies reacting with this 181-320 aa region was further mapped with synthetic peptides, and a peptide (VSLVCEKLCNEKLLKKARIH) recognized by 8 out of 16 sera from both pSS and sSS patients was identified.

Adult↗
PubMed1996

Standardising joint assessment in rheumatoid arthritis.

Evaluating joint involvement in rheumatoid arthritis in a key clinical assessment. We investigated the extent of variation in measurement of joint swelling and tenderness and evaluated the impact of training to standardise methods. Eight observers (medical and nursing staff) examined eight rheumatoid patients for joint swelling and tenderness before and after training in clinical methods. The EULAR handbook for joint evaluation was used for training and assessments were based on the 28 joint count. There was extensive variability in both numbers of swollen and tender joints. Coefficients of variation for articular indices recorded by the 8 observers in individual patients were often high (up to a maximum of 204%), indicating considerable differences between observers. Training had an impact on the assessment of the numbers of swollen joints which increased by a mean of 32% (P < 0.05) and the number of tender joints which increased by 41% (p < 0.01). Training had only a limited impact on the variation among observers in determining the number of swollen and number of tender joints. After training, the mean coefficients of variation were still 59% for swollen joints and 65% for tender joints. These results highlight the extent of variation in clinical assessment of rheumatoid arthritis and show the advantages of training. It leads to increased sensitivity of measurement. Standardisation appears essential for clinical studies.

Analysis of Variance↗
PubMed1996

Agalactosyl IgG [Gal(o)]--an analysis of its clinical utility in the long-term follow-up of patients with rheumatoid arthritis.

This long-term prospective study of patients with newly diagnosed RA assesses the relative value of certain clinical and laboratory measures at first consultation in order to determine factors that help to discriminate between patients likely to go into early remission and those with relapsing/remitting or persistent disease. Validation was sought in a similar group from a separate but comparable prospective study. Measures of clinical activity such as joint score, early morning stiffness (EMS) and acute phase (ESR) improved over 4 yr in both groups, whereas agalactosyl IgG [Gal(o)] levels increased. Using discriminant functional analysis in the first cohort to identify features at entry which would predict outcome at 4 yr, a combination of Gal(o), grip strength, age at onset and gender predicted the course of RA correctly in 95% of the patients. This combination was confirmed in the second cohort, although with reduced power (78% correct). Thus, we show that Gal(o) does not reflect activity of the disease like the ESR, but has greater potential as a prognostic index early in the course of disease.

Arthritis, Rheumatoid↗
PubMed1996

Genetic analysis of TAP2 in systemic lupus erythematosus patients from two ethnic groups.

The aim of this study was to determine whether the TAP2 (Transporter associated with Antigen Processing 2) locus is involved in susceptibility to systemic lupus erythematosus (SLE). We adopted the interethnic approach to overcome problems in the analysis resulting from linkage disequilibrium. The TAP2 gene polymorphisms of the codons corresponding to amino acid positions 379, 565 and 665 were investigated by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) in 186 patients (151 white Europeans, 35 Afrocaribbeans) and 183 controls (79 white Europeans, 104 Afrocaribbeans). In the European SLE patients, the frequency of the TAP2 type V-A-TA was marginally lower compared with the control group (31% vs 42%), with negative linkage disequilibrium between this TAP2 type and DR3 probably accounting for the difference. For the European SLE patients, we confirmed a significant association of DR3 with disease status [odds ratio = 4.16, 95% confidence interval (CI), 2.08-8.39] and in the patients with DR3 there was a significantly high frequency of the TAP2 type V-A-T-. In the Afrocaribbean SLE patients, any associations of disease status with TAP2 phenotype were the inverse of those in the European patients. Thus, in these patients the frequency of V-A-TA was higher than in controls (46% vs 26%, OR = 2.4, 95% CI 1.01-5.74), while the frequency of V-A-T- was lower (26% vs 40%, not significant). Despite possible sampling error, the lack of a difference in TAP2 status between cases and controls within ethnic groups and, if anything, an inverse association across ethnic groups, makes it unlikely that the TAP2 polymorphism studied here is of primary relevance to SLE susceptibility.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Prevalence of self-reported depression in patients with rheumatoid arthritis.

The prevalence of self-reported depressive symptoms was investigated in a case-control study of patients with rheumatoid arthritis (RA) attending an out-patient clinic at the Middlesex Hospital. Patients selected their own controls, matched for age and sex. Previous attempts to measure depressive symptoms in RA have suffered from measurement error due to criterion contamination, where psychological symptoms augment depressive scores. A total of 163 patients (77% of the sample) and 115 matched pairs completed the Hospital Anxiety and Depression Scale (HADS). The results indicated that RA patients are more depressed and anxious than controls. The prevalence of depression above the cut-point was 15%. This figure is comparable to other reports adjusted for criterion contamination, but is lower than that of other studies which employ 'contaminated' tools. The depression scale of the HADS appeared to be relatively free of criterion contamination. Subject to further reliability testing, the HADS may be a practical screening tool for practitioners to assess patients in need of psychological interventions.

Arthritis, Rheumatoid↗