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The article presents a study regarding the high mobility group box1 (HMGB1) in systemic lupus erythematosus (SLE). The study performed in vitro experiments with ultraviolet B (UVB)-irradiated keratinocytes to eleven SLE patients and 10 healthy controls (HCs). The result of the study shows that there was an increase HMGB1 release in the skin of SLE patients compared to HCs.

Fatigue is a major problem in systemic lupus erythematosus (SLE), but the physiological substrate of this fatigue is largely unclear. To examine if low levels of dehydroepiandrosterone (DHEA) and its sulphate DHEAS play a role in SLE fatigue, we compared: 1) DHEAS levels and fatigue between 60 female patients with SLE with low disease activity (31 using, 29 not using prednisone) and 60 age-matched healthy women, and 2) fatigue between patients with SLE with low and normal DHEAS levels. Serum DHEAS levels were determined with an Advantage Chemiluminescense System. The Multidimensional Fatigue Inventory (MFI) was used to assess fatigue. Patients were more fatigued (p ≤ 0.001) than healthy women and more often had below-normal DHEAS levels (p < 0.001). Patients using prednisone with low and normal DHEAS levels reported a similar level of fatigue (p ≥ 0.39). Patients with low DHEAS levels not using prednisone reported less fatigue than those with normal DHEAS levels (p ≤ 0.03). Thus, our results indicate that low DHEAS levels in SLE are not – or even inversely – related to fatigue. After our previous finding that DHEA administration does not reduce fatigue, this result further indicates that low serum DHEA(S) levels alone do not offer an explanation for SLE fatigue. [ABSTRACT FROM AUTHOR]

Objective: Interaction of advanced glycation end products (AGEs) with their receptors (RAGE) plays an important role in inflammation in auto-immune diseases. Several functional polymorphisms of RAGE have been described. In this study we analysed the role of RAGE polymorphisms in disease susceptibility for systemic lupus erythematosus (SLE). In addition, we investigated whether these polymorphisms in SLE are associated with serum levels of soluble RAGE (sRAGE), renal involvement (lupus nephritis (LN)) and its outcome. Methods: For this cross-sectional study DNA samples of 97 SLE patients, 114 LN patients and 429 healthy controls (HC) were genotyped for four RAGE polymorphisms: −429 T/C, −374 T/A, 2184 A/G and Gly82Ser. Differences in genotype frequencies and allele frequencies were tested between patients and HCs. In SLE patients, sRAGE was measured by enzyme-linked immunosorbent assay (ELISA). In addition, association of genotypes with sRAGE and disease severity in LN was analysed. Results: The C allele of −429 T/C, the T allele of −374 T/A and the G allele of 2184 A/G were significantly more prevalent in SLE and LN compared with HC. In LN, the C allele of RAGE −429 T/C, the A allele of −374 T/A and the G allele of RAGE 2184 A/G polymorphism were significantly associated with more proteinuria and worse renal function during the first two years of treatment. No association of genotype with sRAGE was found. Conclusion: RAGE polymorphisms are associated with susceptibility to SLE and LN. In addition, some of these polymorphisms are likely to be associated with disease severity and initial response to treatment in LN. [ABSTRACT FROM PUBLISHER]

The European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) have been recently published. These evidence-based recommendations were based on existing literature in combination with expert opinion. Although patients with AIIRD are at increased risk of suffering from (complicated) infectious diseases – and vaccination seems a tool to reduce this risk – still many questions and controversies remain for the individual patient. In this overview, taking influenza as an example, the background of the recommendations, their clinical implications, and the direction of future research are discussed. The increase in knowledge on vaccine-preventable infections will allow us to further improve vaccination strategies. [ABSTRACT FROM AUTHOR]

B cells, being a source of characteristic antinuclear autoantibodies, play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). Evidences indicate that alterations in B-cell regulation are responsible for B-cell hyperactivity as seen in SLE. T cells, soluble factors, and even B cells themselves regulate effector B-cell functions. The latter, so-called regulatory B cells possess regulatory function through production of the cytokine interleukin-10 (IL-10) that can damp down the humoral immune responses. This review will focus on B-cell regulation in the pathogenesis of SLE as a target for intervention. In particular, the regulatory impact of T cells through costimulation, soluble factors such as B lymphocyte stimulator, and the characteristics of IL 10-producing regulatory B cells will be discussed. Therapies targeting B cells as well as B-cell regulation seem promising, but the precise mechanisms involved in these interventions are not completely understood. More insight into B-cell regulation in SLE, and particularly in regulatory B cells, could lead to novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

As endothelial dysfunction is one of the earliest signs of atherosclerosis, which is accelerated in systemic lupus erythematosus (SLE), we assessed whether vascular responses of the cutaneous microcirculation are disturbed in SLE patients and influenced by Raynaud's phenomenon (RP). Laser Doppler fluxmetry (LDF) was used in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), an endothelium-dependent and endothelium-independent vasodilator respectively. 42 SLE patients with inactive disease, 12 of whom had RP and 19 age- and sex-matched controls were included. Furthermore, traditional and non-traditional risk factors for cardiovascular disease (CVD) were assessed, and markers of inflammation and endothelial activation were measured. Vascular responses of SLE patients without RP did not differ from controls. However, SLE patients with RP exhibited decreased vasodilatation compared with controls. SLE patients with RP also had longer arrival times of ACh and SNP than controls. Markers of inflammation and von Willebrand factor were increased in SLE patients. Smoking, the presence of SLE and RP were negatively associated with vascular responses in univariate analysis. In multivariate analyses, the only independent variable of vascular responses to ACh and SNP was the presence of RP. Despite signs of endothelial activation, SLE patients with inactive disease do not have altered vascular responses in the microcirculation compared with controls. In SLE patients with RP, cutaneous vascular responses to both ACh and SNP are impaired. Therefore, LDF of the microcirculation seems not to be the appropriate method to distinguish those SLE patients with an increased risk to develop CVD. [ABSTRACT FROM AUTHOR]

Chimerism occurs twice as often in the kidneys of women with lupus nephritis as in normal kidneys and may be involved in the pathogenesis of systemic lupus erythematosus. Pregnancy is considered the most important source of chimerism, but the exact relationship between pregnancy, the persistence of chimeric cells and the development of systemic lupus erythematosus has not been investigated. Renal biopsies and clinical data from patients in the First Dutch Lupus Nephritis Study were used. Chimeric cells were identified by in-situ hybridization of the Y chromosome. A questionnaire was used to obtain detailed reproductive data including pregnancy history and miscarriages. Chimerism was found in 12 of 26 (46%) renal biopsies. Of the 12 chimeric women, 5 reported a pregnancy; of 14 women who were not chimeric, 8 reported a pregnancy. Chimeric women who had been pregnant reported significantly more pregnancies than non-chimeric women who had been pregnant (P = 0.04). The median age of the youngest child was higher in chimeric women (19 years) than in non-chimeric women (6 years). Despite the attention given to pregnancy histories with respect to chimerism, this study shows that in patients with systemic lupus erythematosus, a clear-cut relationship is not apparent. A considerable number of chimeric women did not report a pregnancy: in these women, other sources of chimerism must be considered. Our data support the theory that only certain subsets of chimeric cells persist into the maternal circulation after pregnancy. [ABSTRACT FROM AUTHOR]

Although for decades sunlight was suspected to be involved in the development of cutaneous lupus erythematosus (CLE), only in recent years research on the effects of ultraviolet irradiation on the skin of patients with CLE has resulted in a more comprehensive model for the pathogenesis of the disease. In this model, exposure to UV light induces apoptosis of keratinocytes and the release of pro-inflammatory cytokines. In susceptible patients, the presence or even accumulation of apoptotic cells results in the induction of characteristic inflammatory skin lesions, which might be due to a delayed and pro-inflammatory clearance of these apoptotic cells. Many other factors, in part genetically determined, are involved in CLE resulting in a very heterogeneous clinical manifestation. Among these factors, presence of autoantibodies, a decreased number of regulatory T cells at the site of inflammation and increased expression of pro-inflammatory cytokines like TNFα and IFN-inducible protein myxovirus protein A have been shown to play a role in the pathogenesis of CLE. [ABSTRACT FROM AUTHOR]

To determine risk factors of accelerated atherosclerosis in patients with systemic lupus erythematosus (SLE), 72 patients with inactive disease and 36 age- and sex-matched controls were included. The intima-media thickness (IMT) of the common carotid artery was determined by ultrasound. Traditional risk factors and disease-related factors were recorded. Cardiovascular risk was estimated using SCORE (systematic coronary risk evaluation). Markers of inflammation, endothelial activation and vascular remodelling (matrix metalloproteinases (MMP-3, MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1)) were determined. IMT was increased in patients (0.67 mm ± 0.13 versus 0.61 mm ± 0.11, P < 0.05). Prevalence of hypertension (33% versus 6%, P < 0.001), SCORE (2.2 (1.7–4.2) versus 1.7 (1.3–2.1), P < 0.001), as well as parameters of inflammation (CRP 1.8 (0.6–5.8) mg/L versus 0.6 (0.2–1.0) mg/L, P < 0.001) and endothelial activation (VCAM-1 505 (389–683) ng/mL versus 374 (322–427) ng/mL, P < 0.001) and von Willebrand factor (138 (59–208)% versus 48 (24–92)%, P < 0.001), were increased in patients. Vascular remodelling was altered: MMP-3 and TIMP-1 were increased (18 (10–29) ng/mL versus 8 (5–11) ng/mL, P < 0.001, and 275 (216–352) ng/mL versus 230 (197–268) ng/mL, P < 0.001, respectively), and MMP-9 was decreased in SLE (266 (147–412) ng/mL versus 348 (226–530) ng/mL, P < 0.05). Univariate analyses revealed that in patients IMT was associated with age, systolic blood pressure, SCORE and disease duration. In multivariate analysis, age and SCORE were independent predictors of IMT. In conclusion, SLE patients have an increased IMT, which is associated with traditional risk factors. Non-traditional risk factors, such as endothelial activation, altered vascular remodelling and disease duration, might play an additional role. [ABSTRACT FROM AUTHOR]

Serial assessment of levels of autoantibodies has been proposed as being clinically useful in certain systemic autoimmune diseases. In particular, attention has been given to anti-dsDNA antibodies in systemic lupus erythematosus (SLE) and ANCA in the ANCA-associated vasculitides (AAV). Much controversy exists, however, concerning the value of serial testing in these diseases. We here review the various tests available for quantitation of anti-dsDNA and ANCA, and their capacity to detect changes in autoantibody levels that are associated with changes in clinical disease activity of the respective diseases. It is concluded that changes in anti-dsDNA as measured by the Farr assay and changes in ANCA as assessed by ELISA have predictive value for the occurrence of disease relapses, although this relationship is far from absolute. Consequently, treatment based on changes in levels of the respective autoantibodies only seems at present not justified, in view of the toxicity of currently available immunosuppressive regimens. [ABSTRACT FROM AUTHOR]

Levels of apoptotic lymphocytes have been found to be increased in SLE and persistence of apoptotic cells has been associated with autoantibody production. Increased lymphocyte Fas (CD95) expression due to lymphocyte activation may account for increased susceptibility to Fas-mediated apoptosis in SLE. Flowcytometry was performed to evaluate membrane expression of Fas in combination with the activation markers CD25, HLA-DR and CD38 on, respectively, CD4[sup +], CD8[sup +] and CD19[sup +] lymphocytes of SLE patients with inactive (n=20) and with active disease (n=13). SLEDAI-scores were calculated. Healthy volunteers (n=14) served as controls. Percentages of CD4[sup +] T-cells expressing CD25 and CD19[sup +] B-cells expressing CD38 were increased in patients with active disease compared to controls (P=0.03, P=0.04, respectively). In contrast to CD4[sup +] and CD8[sup +] cells, percentages of CD19[sup +] cells expressing Fas were increased in SLE patients with active disease (P=0.0002 vs controls). In these patients percentages of cells double positive for both CD38 and Fas were increased compared to patients with inactive disease (P=0.006) and controls (P=0.0007). Percentages of CD19[sup +] cells expressing Fas correlated with SLEDAI-scores. In SLE patients, percentages of Fas-expressing B-lymphocytes are increased, are related to the state of lymphocyte activation, and correlate to disease activity. Increased Fas expression results in a higher susceptibility for Fas-mediated apoptosis, which might contribute to the increased levels of apoptotic lymphocytes in SLE patients. [ABSTRACT FROM AUTHOR]

Many patients with systemic lupus erythematosus (SLE) develop cardiac manifestations during the course of their disease. Pericarditis is most commonly seen, with a reported prevalence of 60%. Myocardial involvement is present in only a minority of patients. In recent years, due to better non-invasive diagnostic techniques, valvular abnormalities can be demonstrated in an increasing number of patients. Depending on the technique used, valvulopathy can be demonstrated in up to 77% of SLE patients. Although most of the valvular lesions will be present without any symptoms, valve incompetence can result in congestive heart failure. Valvular lesions are associated with IgG anticardiolipin antibodies (aCL) and disease duration. We present a patient with SLE and secondary antiphospholipid syndrome (APS) who developed acute congestive heart failure due to pancarditis. Endocarditis, together with left ventricular dysfunction and pericardial effusion, were present. The endocarditis caused hemody namically significant mitral valve insufficiency due to thickening of the mitral cusps. Just two weeks prior to the occurrence of congestive heart failure echocardiography had been normal. Treatment with high dose corticosteroids resulted in a gradual, almost complete recovery. Literature concerning cardiac manifestations in lupus is reviewed. Lupus (2000) 9, 236–240. [ABSTRACT FROM AUTHOR]