RESULTS: Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29% ABSTRACT ObjectivesTo determine the causes and predictors of mortality in systemic sclerosis (SSc). Methods Patients with SSc (n=5860) fulfi lling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. Results Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fi brosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the nonSSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%).Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modifi ed Rodnan skin score (HR 1.20 per 10 score points). Conclusion Disease-related causes, in particular pulmonary fi brosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.Systemic sclerosis (SSc) is a multisystem disease with vascular, infl ammatory and fi brotic components.

Conclusion. In addition to supporting the role of IFNs in SLE immunopathogenesis in general, the findings of the present study support a role of IFN␥ in this disease.Type I interferons (e.g., IFN␣) and type II IFN (IFN␥) have both been implicated in the immunopathogenesis of systemic lupus erythematosus (SLE). IFN␣ and IFN␥ serum levels are increased (1-5), and IFN messenger RNA (mRNA) signatures are expressed in the peripheral blood cells of SLE patients (6-8). IFN␣ and IFN␥ are known to induce SLE flares and druginduced lupus (9-11). In murine models of the disease, both IFN␣ and IFN␥ may be pathogenetically important (12-15), and, especially, a deficiency in either IFN␥ or the IFN␥ receptor (IFN␥R) totally abates the disease process (16)(17)(18)(19).IFNs act on a variety of cells, including lymphocytes and monocytes (20,21). The biologic effects of IFN␣ and IFN␥ are mediated via the phosphorylation, and thus the activation, of members of the STAT family

Objective. To explore the array of concepts important to patients with chronic systemic lupus erythematosus (SLE) and to compare these with instruments assessing disease activity, damage, and health status. Methods. We conducted a qualitative focus-group study of patients with SLE concerning their problems in daily functioning. The group sessions were tape recorded, transcribed, and divided into meaning units. The concepts contained in these meaning units were extracted and linked to the International Classification of Functioning, Disability and Health (ICF). We then compared the concepts from the focus groups with those concepts covered by SLE activity scores, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and the Short Form 36 Health Survey (SF-36).Results. A total of 92 concepts emerged from 5 focus groups; of these, 28 related to body functions and structures, 24 to activities and participation, and 25 to environmental factors. Two concepts were linked to the health condition itself and 6 to personal factors. Seven were not covered by the ICF. Of the 28 concepts regarding body functions and structures, 24 (86%) were covered by the combination of activity scores and the SDI. The SF-36 also addressed 3 of these concepts and contained 9 (38%) of 24 concepts in activities and participation. Conclusion. Although the combination of SLE activity scores, SDI, and SF-36, as suggested for SLE studies, well covers body functions and structures and includes a significant portion of problems regarding activities and participation, neither environmental nor personal factors are covered at all. KEY WORDS. Systemic lupus erythematosus; International Classification of Functioning, Disability and Health; Patient perspective. INTRODUCTIONThe World Health Organization's International Classification of Functioning, Disability and Health (ICF) (1) is a tool used to better characterize the full array of problems a patient faces when affected with disease (2-4). Specifying these problems is a particular challenge in a disease such as systemic lupus erythematosus (SLE) because of the wide variety of organ systems involved and its variable activity and severity.SLE is a prototypical autoimmune disease with an incidence and prevalence varying considerably in different countries (5,6). The burden of the disease is elevated Arthritis & Rheumatism (Arthritis Care & Research) Vol. 57, No. 7, October 15, 2007, pp 1287-1295 DOI 10.1002/art.23013 © 2007, American College of Rheumatology ORIGINAL ARTICLE 1287 among nonwhite racial groups. There is a trend toward higher incidence and prevalence of SLE in Europe and Australia compared with the US. In Europe, the highest prevalence was reported in Sweden, Iceland, and Spain (7). Patients with SLE commonly experience combinations of various organ symptoms, which often include joints, skin, kidney, or central nervous system (CNS) disease, but can also affect essentially all other organ systems (8,9). SLE also varies in disease activit...

In systemic lupus erythematosus (SLE) serum TNF is increased and correlates with its soluble receptors and with disease activity. We therefore investigated (i) whether the TNF in SLE serum is bioactive, (ii) whether SLE cells react to TNF and (iii) whether there are associations with cell death, which is regarded as pathogenic in SLE. Sera from active SLE patients induced an increase in fibroblast CD54, which was abolished by blocking antibodies against TNF, suggesting TNF bioactivity. SLE lymphocytes had a similar surface expression of TNF-RI as healthy lymphocytes, their expression of TNF-RII was slightly increased. Recombinant TNF induced cell death in PBMC of SLE patients, suggesting functional receptors. Serum levels of sTNF-RII (as a surrogate marker for TNF activity) correlated with sTNF-RI and disease activity, as expected, and also correlated with the percentage of dying lymphocytes and with lymphocytic CD95. SLE sera contain increased amounts of biologically active TNF. Peripheral blood lymphocytes of SLE patients express functional TNF receptors. Finally, associations with cell death and CD95 receptors suggest that TNF may be pathogenic in SLE.

The LE cell has been one of the first immunological signs of active systemic lupus erythematosus, included into the ACR criteria. LE cells consist of a phagocyte engulfing material of disputed origin, which was interpreted as either cellular remnants from necrotic cells or as early apoptotic cells. It is well established that LE cell formation is dependent on autoantibodies against the linker histone H1. In view of this fact, we investigated whether anti-histone H1 antibodies and LE cell positive sera bound to cells where apoptosis had been induced by gliotoxin or actinomycin D or which were necrotic after heating. Necrotic cell remnants, but not (early) apoptotic cells were bound by anti-histone H1 antibodies and LE cell positive sera, establishing that the process of LE cell formation, which is dependent on anti-H1 binding, leads to engulfment of necrotic (or late apoptotic) material, but not of early apoptotic cells.