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SLE
SLE Patients with a disease duration < 3 years
An international, multicenter study under the supervision of the Eular Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCICS).
Study objective:
1. To describe the early disease course in patients with Systemic Lupus Erythematosus with respect to severity of early disease activity, development of organ damage and causes of early death.
2. To provide data on the need and/or desirability of early, aggressive treatment to prevent
disease induced damage
Design: A multicentre study of all patients diagnosed with SLE since 1-1-1997 at the various participating institutes.
Inclusion criteria: Only patients fulfilling the updated ACR criteria (1997) will be included. Time of diagnosis defined as moment of fulfilling 4 or more updated ACR classification-criteria.
Exclusion criteria: Patients with a disease duration longer than 3 years after study-start.
Primary study parameters: a. longitudinal disease activity index /damage Index
b. causes of early death (SLE-related or other)
Secondary parameters: c. age at onset
d. specific organ involvement
e. need for medication (mean/cumulative dosage)
Study size: At least 150 patients must be included to allow comparison of these data with the previous data obtained in patients with a disease duration longer than 10 years. Comparing these results will lead to information if the timing of disease activity (i.e. early vs. late) is important in determining outcome cq damage in SLE. For the study of mortality however, assuming a 5 year cumulative survival of 90% , at least 300 SLE patients must be taken in the study to reach a meaningful study cohort.
Data collection: All information from the patients will be obtained by the physicians involved in the study at each centre. These data are recorded in the patient record book at the start of the study and then annually during a 5 year period of time by assessing extent of organ damage (SLICC/ACR Damage Index) and disease activity (ECLAM +SLEDAI) during that period. For every nonsurviving patient, cause of death will be studied in detail as described in the separate protocol for the study on causes of death in all SLE patients.
Publications: All data will be registered in a computerised database. Information derived from the study will be presented in relation to EULAR workshops-congresses. Several original articles are expected to be written with the information obtained from this study. Authorship of these publications will be established with agreement of all participating centres. In addition each centre can make use of the data obtained from its own patients for its own publications
Current causes of death in Systemic Lupus Erythematosus in Europe: results of a multicenter study under the auspices of ESCISIT-EULAR
Aim
To describe current causes of death in a large multinational cohort of European SLE patients in relation to disease duration, activity and damage.
Methods
Observational study with twelve participating centres recording the direct and contributory causes of death in patients with SLE throughout a five year period. Demographics, disease duration, previous disease manifestations and therapeutic interventions, concurrent disease activity (by ECLAM and SLEDAI) and damage (by SLICC-DI) at the time of death will be recorded and related to the cause of death.
K. Manger, J. R. Kalden. Department of Internal Medicine III and Institute for Clinical Immunology, University Erlangen-Nurnberg, Erlangen, Germany.
A. Marchesoni, S. Tosi. Rheumatology Unit, Istituto Ortopedico Gaetano Pini, Milano, Italy.
Z. Domljan, A. Branimir, N. Cikes.Department of Rheumatology, University Hospital, Zagreb, Croatia.
D. Logar, B. Rozman, Department of Rheumatology, Dr Peter Drzaj Hospital, Ljubljana, Slovenia.
L. Kovacs, G. Pokorny, First Department of Internal Medicine, Szent-Gyorgyi Medical University Centre, Szeged, Hungary.
A. Kovacs, Bloodtransfusion Institute, Dr A. Szent-Gyorgyi Medical University Centre, Szeged, Hungary.
P. G. Vlachoyiannopoulos, H. M. Moutsopoulos.Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece.
B. Dratwianka, H. Chwalinska-Sadowska, Department of Connective Tissue Diseases, Institute of Rheumatology, Warsaw, Poland.
E. Kiss, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary.
R. Fischer, M. Schneider, Medical Clinic, Department of Rheumatology, Heinrich-Heine University, Dusseldorf, Germany.
M. Mosca, S. Bombardieri, Universita degli Studi di Pisa, Dipartimenti di Medicina Interna, Italy.
W. Graninger, J. S. Smolen, Department of Rheumatology, University of Vienna, Vienna, Austria.
A. J. G. Swaak, Department of Rheumatology, Ikazia ziekenhuis, Rotterdam, The Netherlands.
H. Nossent, Dept. of Rheumatology, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.
Alpha-actinin binding antibodies: specificity for Systemic Lupus Erythematosus and relation to anti-dsDNA antibodies and nephritis
A wide spectrum of non-organ specific autoantibodies can be demonstrated in the serum of patients with Systemic Lupus Erythemaosus (SLE). While the clinical significance of many of these autoantibodies remains unclear, anti-dsDNA antibodies are among the most SLE specific autoantibodies and are also involved in the pathogenesis of lupus nephritis (LN). Given the severe consequences of LN in terms of comorbidity, mortality and/or treatment related toxicity, increased knowledge on the pathophysiology of LN is needed to develop more rational therapeutic interventions. Intraglomerular immunecomplex depositions are a hallmark of LN and anti-dsDNA antibodies can be eluted from affected kidneys in both human and experimental LN. The glomerular binding site for anti-dsDNA antibodies is however still unknown . The α-actinins are rod-shaped proteins important in the organization of the cytoskeleton as they bind and crosslink actin; it consists of two identical antiparallel dimers of 94-103 kDa and is detected in both muscle and non-muscle cells. In non-muscle cells, α-actinin plays an important role in the assembly of adhesion receptors such as integrins and cadherins. Via these adhesion plaque proteins α-actinin provides a link between the cytoskeleton and the extracellular matrix (ECM). In the kidney, α -actinin has been detected in mesangial cells, podocytes, capillaries, and larger blood vessels. After puromycin aminonucleoside injection glomerular α -actinin expression increases prior to foot processes confluence and proteinuria, suggesting a role for α -actinin in renal pathophysiology. In addition, mutations in the human α -actinin-4 gene are involved in the development of familial focal and segmental glomerulosclerosis. There is also evidence that α-actinin is present in the extracellular footpad material of cells adhesion sites, as a result of normal movement of cells and that influx of inflammatory cells increases the amount of extracellular α-actinin, possibly as an aid in monocyte/macrophage maturation. Recent reports have indicated that anti-dsDNA antibodies may specifically cross react with intraglomerular α-actinin in patients with LN. However in view of the abovementioned it seems improbable that the intraglomerular presence of non-muscle α–actinin would be specific for patients with LN. Therefore, we investigated the presence of α–actininin binding antibodies in patients with various autoimmune systemic inflammatory diseases, including SLE. Furthermore, as anti-dsDNA antibodies are thought to mediate their nephritogenic potential in SLE patients through cross-reactive α-actinin binding, we analyzed in more detail the associations between α-actinin binding and clinical and immunological manifestations in SLE patients.
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