Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus.

An inception cohort of patients with systemic lupus erythematosus from 14 European centres was followed for up to 5 years in order to describe the current early disease course. At inclusion patients (n = 200, 89% female, mean age 35 years, 97% Caucasian, mean SLEDAI 12.2) fulfilled a mean of 6.

Increased ferritin response in adult Still's disease: specificity and relationship to outcome.

Background: The disproportionate ferritin response encountered in some patients with adult Still's disease (ASD) may reflect a fundamental aspect in the pathophysiology of ASD.

Methods: An observational case-control study of 22 ASD patients followed for 63 months. Baseline laboratory data were compared with age- and gender-matched controls with new-onset rheumatoid arthritis (RA).

Renal immunofluorescence and the prediction of renal outcome in patients with proliferative lupus nephritis.

The risk for endstage renal failure in patients with proliferative lupus nephritis (PLN) depends largely on the severity and reversibility of the inflammatory process as determined by light microscopy (LM). As the intrarenal formation of immune complexes is thought to initiate this inflammation, we studied whether renal immunofluorescence microscopy (IFM) provides clinical or prognostic information in addition to LM findings. Clinical data at the time of renal biopsy and during a mean follow-up of 46 months were extracted from the records of 69 SLE patients with proliferative LN (WHO class III/IV).

Isolated hepatic perfusion in the pig with TNF-alpha with and without melphalan.

Isolated limb perfusion with tumour necrosis factor alpha (TNF-alpha) and melphalan is well tolerated and highly effective in irresectable sarcoma and melanoma. No data are available on isolated hepatic perfusion (IHP) with these drugs for irresectable hepatic malignancies. This study was undertaken to assess the feasibility of such an approach by analysing hepatic and systemic toxicity of IHP with TNF-alpha with and without melphalan in pigs.

Functional analysis of synovial fluid and peripheral blood T cells from patients with rheumatoid arthritis.

Rheumatoid arthritis is a T cell-mediated autoimmune disease. The lack of knowledge of the involved target antigens severely hampers research on relevant T cells in patients. Here we describe the functional analysis of freshly isolated T cells from the peripheral blood and the site of the lesion (synovial fluid or synovial membrane) of patients with rheumatoid arthritis.

Clinical significance of maternal anti-Ro/SS-A antibodies in children with isolated heart block.

Objectives: We studied 30 consecutive children with isolated heart block to assess the clinical impact of the presence of maternal anti-Ro/SS-A antibodies for isolated heart block.

Background: Isolated heart block in children, often associated with maternal autoimmune disease leading to anti-Ro/SS-A auto-antibody production, is an infrequent but potentially lethal disorder.

Methods: Thirty children with isolated heart block were studied with respect to medical history and electrocardiographic (ECG) analysis.

Responses of synovial fluid and peripheral blood mononuclear cells to bacterial antigens and autologous antigen presenting cells.

The specificity of T cells in the inflamed joints of patients with rheumatoid arthritis (RA) has been the subject of much study. Bacterial antigens are suspect in the aetiology of rheumatic diseases. The responsiveness of the mononuclear cell fraction of peripheral blood and synovial fluid of patients with RA and of patients with rheumatic diseases other than RA to bacterial antigens such as cell wall fragments of the anaerobic intestinal flora, cell wall fragments of Streptococcus pyogenes, intestinal flora derived peptidoglycan polysaccharide complexes, the 65 kilodalton protein of Mycobacterium tuberculosis, and muramyldipeptide was investigated.

Proteolytic inactivation of alpha 1-antitrypsin and alpha 1-antichymotrypsin by neutrophils in arthritic joints.

Objective: In vitro, activated neutrophils create a microenvironment in which proteinase inhibitors are inactivated through the coordinate action of reactive oxygen species and released elastase. We investigated whether such a mechanism may contribute to the destruction of the joint tissues in arthritis.

Methods: We analyzed the state of alpha 1-antitrypsin (alpha 1AT) and alpha 1-antichymotrypsin (alpha 1ACT), the two major inhibitors of the neutrophilic serine proteinases, in synovial fluid (SF) from patients with inflammatory arthropathies (n = 71) and osteoarthritis (OA) (n = 11), and related the results to neutrophil activation in SF.

Analysis of intraarticular fibrinolytic pathways in patients with inflammatory and noninflammatory joint diseases.

Objective: Intraarticular activation of the fibrinolytic system has been suspected to occur in patients with arthritis. We undertook the present study to investigate the relation of this activation to clinical symptoms, and the molecular pathways involved.

Methods: We quantitatively assessed levels of plasmin-alpha 2-antiplasmin (PAP) complexes in synovial fluid (SF) from 25 patients with rheumatoid arthritis (RA), 7 with seronegative spondylarthropathy (SSA), and 10 with osteoarthritis (OA), and conducted an analysis to determine the plasminogen-activating pathway via which these complexes were generated.

Diagnostic value of antibodies against ribosomal phosphoproteins. A cross sectional and longitudinal study.

Antibodies against ribosomal phosphoproteins (anti-P antibodies) are found in about 10% of patients with systemic lupus erythematosus (SLE). Using an ELISA with a synthetic peptide for screening and an immunoblotting technique as a confirmation test for detection of these antibodies, we found 16 positive patients among 946 sera sent to our reference laboratory for anti-DNA determination. All 12 patients on which we could obtain clinical data had clearcut SLE, fulfilling 6 ARA criteria on average.

Sjögren syndrome: comparative studies in local ocular and serum immunoglobulin concentrations with special reference to secretory IgA.

The objective of the present study was to examine Secretory IgA in tears and serum of Sjögren patients (34 patients and 23 controls). The test was performed in a parallel study using a polyclonal and a monoclonal method (Inter-Assay variation 9.1/Intra-Assay variation 5.

Renal tubular dysfunction in primary Sjögren's syndrome: clinical studies in 27 patients.

Kidney involvement in Sjögren's syndrome (SS) including renal tubular disorders are well recognized but little is known about frequency and extent of such dysfunction in the general population of patients with primary SS, due to a lack of group studies. We studied 27 patients with primary SS and without other possible causes of tubular dysfunction. Increased urinary beta 2M excretion, due to proximal tubular dysfunction, was present in 26% of patients.

Systemic lupus erythematosus after renal transplantation: patient and graft survival and disease activity. The Dutch Working Party on Systemic Lupus Erythematosus.

Objective: To determine the outcome of renal transplantation in patients with systemic lupus erythematosus and end-stage renal failure and to compare disease activity after transplantation with disease activity before transplantation.

Design: Retrospective case finding using data for an 8-year period from the central registry for renal replacement therapy in The Netherlands.

Setting: Tertiary care hospitals with facilities for renal transplantation in the Netherlands.

Systemic lupus erythematosus: analysis of disease activity in 55 patients with end-stage renal failure treated with hemodialysis or continuous ambulatory peritoneal dialysis. Dutch Working Party on SLE.

Purpose: To compare disease activity in patients with systemic lupus erythematosus (SLE) (1) before and after the onset of end-stage renal failure and (2) during hemodialysis and continuous ambulatory peritoneal dialysis (CAPD).

Patients And Methods: Records of 55 patients with SLE currently being treated with dialysis were reviewed. Disease activity was measured according to the SLE Disease Activity Index, event rates per 1,000 months' patient observation, and use of medication.

Contribution of renal biopsy data in predicting outcome in lupus nephritis. Analysis of 116 patients.

We reassessed renal biopsy specimens from 116 patients with systemic lupus erythematosus and clinical manifestations of lupus nephritis to determine the contributions of the World Health Organization classification system, the activity and chronicity indexes of the National Institutes of Health scoring system, and various clinical parameters at the time of biopsy to predicting disease outcome. Multivariate analysis showed that only a chronicity index greater than 3 was predictive for decreased renal survival, while age greater than 31 years at biopsy and a chronicity index greater than 3 were associated with decreased patient survival. Clinical tests of renal function were not reliable in discriminating between active lesions and chronic renal damage.

Systemic lupus erythematosus. VI. Analysis of the interrelationship with pregnancy.

The influence of systemic lupus erythematosus (SLE) on pregnancy and vice versa was examined during 39 pregnancies in 19 patients, and outcome was compared with 24 pregnancies in 18 other patients before SLE was established. No difference in fetal loss or premature birth rate was found, although more babies were born with low birth weight after SLE was diagnosed; there was a preponderance of female babies in both groups. Pregnancy during SLE was accompanied by disease exacerbations in up to 74% of all patients.

A comparison of assays used for the detection of antibodies to DNA.

In this paper we will briefly compare four assays in use in our institute for the measurement of antibodies to DNA: the anti-DNA ELISA, the PEG assay, the indirect immunofluorescence test on Crithidia luciliae and the Farr assay. Although with the use of sera from defined patients with systemic lupus erythematosus (SLE) quite good correlations were obtained between the various assays, these correlations were lost upon the use in routine screening of sera of undefined patients. It will be shown that the Farr assay has the highest specificity to systemic lupus erythematosus, whereas the ELISA and the PEG assay are the most sensitive methods.

Antibodies to DNA in patients with systemic lupus erythematosus. Their role in the diagnosis, the follow-up and the pathogenesis of the disease.

In this paper an overview of the present knowledge on antibodies against DNA will be presented. Diagnostic, prognostic and pathogenic aspects of anti-DNA will be highlighted. Detection of antibodies to DNA in the circulation of a patient by an assay selective for high avidity anti-DNA is highly diagnostic for SLE.

Dissociation studies of DNA/anti-DNA complexes in relation to anti-DNA avidity.

Antibodies to dsDNA differ in their avidity towards the antigen. The electrostatic interaction between DNA and anti-DNA is sensitive to increases in pH and/or ionic strength and therefore, elution studies employing either of these permit discrimination between anti-dsDNA populations that differ in avidity. Another way to determine anti-dsDNA avidity is the calculation of Farr/PEG ratios.

Is anticardiolipin activity a cross-reaction of anti-DNA or a separate entity?

Putative cross-reactions between anti-DNA and anticardiolipin activities were studied using sera of different patients and a panel of monoclonal antibodies to DNA. Sera were obtained from patients with systemic lupus erythematosus, from patients with syphilis, and from heroin addicts who showed a biologic false-positive result on the serologic test for syphilis. While the patients with syphilis and the heroin addicts had elevated levels of anticardiolipin antibodies in their circulation, no reactivity with DNA was observed in these sera.

Clinical significance of antibodies to double stranded DNA (dsDNA) for systemic lupus erythematosus (SLE).

In sera of patients with systemic lupus erythematosus (SLE) a wide variety of antibodies against nuclear antigens can be found, including antibodies to nucleic acids, histones and non-histone nuclear proteins. Among these, antibodies to double stranded DNA (dsDNA) appear to be mainly restricted to SLE. Yet, in daily practice one also finds patients that have antibodies to dsDNA during a long time ( greater than 5 years) but have not developed SLE.

Complement-fixing antibodies to dsDNA detected by the immunofluorescence technique on Crithidia luciliae. A critical appraisal.

Studies using an adapted immunofluorescence technique (IFT) on Crithidia luciliae to determine the complement fixing ability of antibodies to dsDNA in relation to disease manifestations, i.e., nephritis, have yielded conflicting results.