Serum and urine TNF-like weak inducer of apoptosis, monocyte chemoattractant protein-1 and neutrophil gelatinase-associated lipocalin as biomarkers of disease activity in patients with systemic lupus erythematosus.

OBJECTIVES: TNF-like weak inducer of apoptosis (TWEAK), monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) are proinflammatory cytokines/chemokines that are considered as potential biomarkers reflecting disease activity in systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and extra-renal SLE. METHODS: Thirty active patients with SLE (15 renal and 15 extra-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 extra-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. RESULTS: Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared to the inactive SLE group (sTWEAK p = 0.005; uTWEAK p = 0.026; sNGAL p < 0.001; uNGAL p = 0.002), whilst no significant differences regarding serum and urine MCP-1 levels were observed (p = 0.189 and p = 0.106, respectively). uTWEAK (p = 0.237), sMCP-1 (p = 0.141), uMCP-1 (p = 0.206), sNGAL (p = 0.419) and uNGAL (p = 0.443) levels did not differ between patients with active renal and extra-renal SLE. Serum TWEAK was higher in patients with active renal SLE (p = 0.006). There were no differences between active renal SLE and active renal AAV. Levels of all biomarkers were correlated with the SLE Disease Activity Index. CONCLUSION: sTWEAK, uTWEAK, sNGAL and uNGAL are biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV.

Autoimmune haemolytic anaemia and thrombocytopaenia in a single-centre cohort of patients with systemic lupus erythematosus from Turkey: clinical associations and effect on disease damage and survival.

INTRODUCTION: Thrombocytopaenia and autoimmune haemolytic anaemia (AIHA) have considerable impact on prognosis in systemic lupus erythematosus (SLE). We investigated the frequencies of these haemocytopaenias, along with their associations and effect on outcome in a single-centre cohort of patients with SLE. METHODS: Demographic characteristics, clinical features, autoantibody profiles, damage and mortality data were compared between patients with and without each haematological abnormality. Variables displaying significant differences between the groups were entered into logistic regression. RESULTS: Ninety-three patients had AIHA and 215 had thrombocytopaenia. Both were associated with neuropsychiatric (NP) involvement, with each other, leucopaenia, antiphospholipid syndrome (APS) and antiphospholipid antibodies. More patients in both groups had organ damage, and their damage scores were higher. Association to NP damage was discernible. In addition, cardiovascular and renal damage and diabetes were more pronounced in patients with thrombocytopaenia. At logistic regression analysis, younger age, anticardiolipin antibody IgM positivity, leucopaenia and thrombocytopaenia were associated with AIHA whilst lupus anticoagulant activity, AIHA, leucopaenia, APS and NP involvement were associated with thrombocytopaenia. Among damage items, peripheral vascular damage, diabetes, NP damage, renal and ocular damage displayed significant associations with thrombocytopaenia, whereas none of the items did with AIHA. Patients with AIHA had significantly reduced survival rates at 10 and 20 years. CONCLUSIONS: We observed that AIHA and thrombocytopaenia were associated with severe lupus, affecting major organs and causing end organ damage. Thus, they may be considered as prognostic markers. Furthermore, AIHA and especially thrombocytopaenia may also be a marker for a subgroup of lupus patients who have or may develop APS.

Domain I of ß2GPI is capable of blocking serum IgA antiphospholipid antibodies binding in vitro: an effect enhanced by PEGylation.

OBJECTIVES: This study aims to inhibit antiphospholipid syndrome (APS) serum derived IgA anti-beta-2-glycoprotein I (aß2GPI) binding using Domain I (DI). METHODS: Serum from 13 APS patients was tested for IgA aß2GPI and Anti-Domain I. Whole IgA was purified by peptide M affinity chromatography from positive serum samples. Serum was tested for IgA aß2GPI binding in the presence and absence of either DI or of two biochemically modified variants containing either 20 kDa of poly(ethylene glycol) (PEG) or 40 kDa of PEG. RESULTS: Significant inhibition with DI was possible with average inhibition of 23% (N = 13). Further inhibitions using 20 kDa PEG-DI and 40 kDa PEG-DI variants showed significant inhibition (p = 0.0001) with both the 40 kDa PEG-DI and 20 kDa PEG-DI variants showing increased inhibition compared with DI alone (p = 0.0001 and p = 0.001, n = 10). CONCLUSIONS: Inhibition of IgA aß2GPI by DI is possible and can be enhanced by biochemical modification in a subset of patients.

Increased serum leptin levels are associated with metabolic syndrome and carotid intima media thickness in premenopausal systemic lupus erythematosus patients without clinical atherosclerotic vascular events.

Aim To assess subclinical atherosclerosis and the role of inflammatory mediators, vascular endothelial cell activation markers and adipocytokines in systemic lupus erythematosus (SLE) in the presence or absence of metabolic syndrome (MetS). Methods We studied 66 premenopausal female SLE patients (20 with MetS) and 28 female healthy controls (HCs) without history of cardiovascular disease (CVD). Subclinical atherosclerosis was screened by measuring carotid intima media thickness (CIMT). Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor α (TNFα), interleukin 6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin, leptin and visfatin were measured. Results The mean age of MetS+SLE, MetS- and HC were 38.3 ± 6.7, 32.7 ± 9.3 and 29.9 ± 5.6 years, respectively. The mean disease duration, SLICC (Systemic Lupus International Collaborating Clinics damage index) and Systemic Lupus Erythematosus Disease Activity Index scores were 74.8 ± 54.9 months, 0.16 ± 0.48 and 1.18 ± 1.5, respectively, and were similar between MetS+and MetS- SLE patients. CIMT values were higher in both MetS+ and MetS- SLE patients than HCs ( p < 0.001). sICAM-1 and erythrocyte sedimentation rate levels were higher in both MetS+ and MetS- SLE patients than HCs ( p < 0.001; p = 0.002, p = 0.001). The SLE MetS+ group had higher CIMT values than SLE MetS- (right: p = 0.003; left: p = 0.025). Leptin levels and homeostatic model assessment (HOMA) scores were significantly higher in SLE MetS+ than SLE MetS- ( p = 0.018; p = 0.04). Leptin and CRP levels and body mass index, SLICC and HOMA scores were correlated with CIMT values (right: p = 0.03, p < 0.001, p < 0.001, p = 0.026 and p < 0.001, and left: p = 0.028, p = 0.03, p = 0.003, p = 0.002 and p = 0.025). Conclusions In premenopausal women with SLE without a history of CVD, CIMT values were increased and related to MetS. Leptin was increased in patients with MetS and correlated with CIMT values.

Metabolic syndrome is not only a risk factor for cardiovascular diseases in systemic lupus erythematosus but is also associated with cumulative organ damage: a cross-sectional analysis of 311 patients.

BACKGROUND/PURPOSE: Patients with systemic lupus erythematosus (SLE) have increased rates of cardiovascular disease (CVD) that are one of the major causes of mortality. The aim of this study was to determine the frequencies of metabolic syndrome (MetS) and CVD in SLE patients and investigate the link between these and clinical features of SLE. METHODS: A total of 311 SLE patients were consecutively assessed for cumulative organ damage (SDI/SLICC scores), history of CVD and MetS as defined by the National Cholesterol Educational Program Adult Treatment Panel III (NCEP ATP III). Clinical data of SLE patients were collected from the records. RESULTS: The mean age of the patients was 40.2 ± 13.4 years and 89% were female. The frequencies of CVD and MetS were 15.2% and 19%, respectively. In this SLE cohort increased age, cumulative damage, disease duration and CVD were associated with MetS. CVD was associated with disease duration, cumulative damage, pericarditis, hematologic involvement, lymphopenia, thrombocytopenia, neurological involvement and antiphospholipid antibody (aPL) positivity. Hydroxychloroquine (HCQ) use was found as a protective factor for CVD. CONCLUSION: In SLE patients, MetS was associated with CVD and both increased with disease duration. Patients who developed MetS and/or CVD had increased cumulative organ damage. Certain clinical features of SLE and the presence of aPL were also associated with CVD. There was a significant protective effect of HCQ from CVD. The prevention of MetS and long-term use of HCQ may be beneficial in improving the prognosis of SLE.

Favourable pregnancy outcome in Takayasu arteritis: a single-centre experience.

OBJECTIVES: Takayasu arteritis is a chronic large-vessel vasculitis in young women of reproductive age. We aimed to obtain information on pregnancy in TA retrospectively. METHODS: Takayasu arteritis patients with history of pregnancy were included in this study. The evaluations included physical findings, serum C-reactive protein, erythrocyte sedimentation rate as well as history and symptoms. Information about pregnancies, abortus, deliveries and newborns was obtained from medical records. Disease activity score, disease damage index appraised Kerr's criteria and vasculitis damage index (VDI) and medication were recorded. RESULTS: Thirty-six Takayasu arteritis patients who had a total of 84 pregnancies were evaluated. The mean age of patients ranged 24.5 ± 6.6 years. Subclavian arteries (86%) were the most frequently involved vessels. We were able to complete the follow-up of ten patients who had a pregnancy after diagnosis during the period of pregnancy. Two patients who had renal artery involvement and active disease in third trimester suffered from preeclampsia and a worsening of hypertension. In one of them, disease flared up in the third trimester. There was no active disease in the postpartum sixth month. Maternal heart failure, cerebrovascular accident, death or cerebral hypoperfusion at the time of delivery, asphyxia and newborn anomalies were not seen in any of these patients. CONCLUSIONS: TA pregnancies may have a favourable outcome with regular follow-up schedule and close monitorisation of blood pressure.