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Longitudinal studies on cognitive impairment in patients with past history of neuropsychiatric lupus (NPSLE) are scant. In this study, NPSLE patients and matched disease and healthy controls were examined with a full battery of neuropsychological tests that covered eight cognitive domains at two time-points 12 months apart. Confounders, including depressive and anxiety symptoms, were measured by the Hospital Anxiety and Depression Scale. Eighteen NPSLE, 18 patients with systemic lupus erythematosus (SLE) who had no previous cerebral involvement (non-NPSLE) and 16 healthy subjects were recruited. NPSLE patients consistently reported more cognitive and anxiety symptoms than non-NPSLE patients over both time-points. NPSLE patients had significantly worse memory, simple and complex attention compared to non-NPSLE patients, among which memory remained significantly impaired after adjustment for confounders. NPSLE patients demonstrated a trend of higher raw scores of some neurocognitive tests upon re-evaluation over 12 months, but NPSLE patients did not demonstrate any practice effect. In conclusion, NPSLE patients had significantly worse and persistently impaired memory and learning deficits compared to non-NPSLE patients over the 12-month re-assessment period. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) has been considered as stem cell disorder. The objective of this study was to examine the phenotype, growth and immunomodulatory effect of mesenchymal stem cells (MSCs) from SLE patients compared with those from age- and sex-matched healthy donors. MSCs were expanded from bone marrow aspirate and were examined for morphological appearance, quantified in different passages to determine growth rate and evaluated for ability of adipogenesis and osteogenesis. Telomerase activity was measured by telomerase repeat amplification protocol. The immunomodulatory effect of MSCs was evaluated by mixed lymphocyte reaction. MSCs from SLE patients were found to be bigger and flattened in appearance after passage 3 and demonstrated slower growth rate compared with fibroblast-like MSCs from normal controls. These cells were not able to reach confluence after passage 4. Telomerase activity was upregulated in five SLE patients mostly with active disease compared with two with negative expression with lesser activity. MSCs from SLE patients were, otherwise, comparable to normal controls in terms of their surface marker (CD73, CD90 and CD105) expression and extent of suppression on proliferation of allogeneic T lymphocytes. In conclusion, MSCs from SLE demonstrated early signs of senescence which may be a corollary of active lupus or a contributory factor to disease pathogenesis. [ABSTRACT FROM AUTHOR]

Patients with systemic lupus erythematosus (SLE) are susceptible to the development of lymphoproliferative disorders and postulated causes include intrinsic defects in immune surveillance and iatrogenic administration of immunosuppressants. Since the introduction of mycophenolate mofetil (MMF) to the immunosuppressive regimen for the management of post-organ transplantation, there have been reports of primary lymphoma of the central nervous system (PCNSL). MMF has been widely used to treat active SLE patients with Class IV lupus nephritis. In addition to two previously reported cases of PCNSL among SLE patients on long-term MMF, we report a third patient who has been on treatment with MMF for 8 years. The histology showed features compatible with diffuse large B-cell lymphoma with strong immunohistochemical staining for CD20 and positive signal for Epstein-Barr virus (EBV)-encoded RNA by in-situ hybridization that is similar to other case reports, suggesting EBV driven B-cell lymphoproliferative disease. The patient responded to withdrawal of MMF, intravenous methotrexate, rituximab and whole brain radiotherapy. With the increasing use of MMF in active renal as well as non-renal exacerbations of SLE, PCNSL should be included in the differential diagnosis in patients who present with gradual onset of focal neurological deficit. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE) is uncommon but is associated with poor survival. This study aimed to examine the long-term effects of bosentan, a dual endothelin-1 receptor antagonist, on symptomatology, haemodynamics and quality of life measures in SLE patients with symptomatic PAH. Four local patients had been followed up prospectively with pre-defined protocol during 12-months of bosentan treatment. Six minute walk distance (6MWD), NYHA functional class, Borg Dyspnoea Index (BDI) and SF-36 were measured at 0, 3, 6, 9 and 12 months. Systolic pulmonary arterial pressure (PAP) was measured by transthoracic echocardiography at zero, six and 12 months. Clinical parameters were analysed, pooling data from other SLE patients reported in the literature (n = 4). Bosentan was found to result in significant improvement in 6MWD compared to baseline [+24.8 m, +26.2 m, +54 m and +62.7 m at three (P = 0.001), six (P = 0.001), nine (P = 0.24) and 12 (P = 0.01) months respectively]. A differential effect was found with greater response in patients with lower exercise capacity. This was accompanied by decrease in NYHA functional class, BDI, transient or sustained drop in systolic PAP and mild improvement in SF-36 domains including mental health, vitality, social function and general health. Significantly deranged liver function was found in one patient. [ABSTRACT FROM AUTHOR]

Background and Purpose: Patients with neuropsychiatric systemic lupus erythematosus have worse outcomes compared with those with systemic lupus erythematosus. A better understanding of the mechanisms of neuropsychiatric systemic lupus erythematosus could potentially improve diagnosis and management. The goal of this study was to investigate the differences in the structural brain network of patients with neuropsychiatric systemic lupus erythematosus compared with patients with systemic lupus erythematosus by using brain connectivity analysis., Materials and Methods: We recruited 20 subjects for each patient cohort and age-matched healthy controls. The topology and efficiency of the network and the characteristics of various brain hubs were investigated by using brain connectivity analysis of diffusion MR imaging data., Results: There were more extensive reorganizations in the structural brain network of patients with neuropsychiatric systemic lupus erythematosus than in patients with systemic lupus erythematosus. For example, the network of the former had significantly decreased clustering coefficient and local efficiency. They also had significantly lower nodal efficiency in the superior temporal gyrus (P = .046) and middle temporal gyrus (P = .041)., Conclusions: Our results hint at a plausible relationship between the neuropsychiatric symptoms and reorganization of the structural brain network of patients with systemic lupus erythematosus. Brain connectivity analysis may be a potential tool to subtype these patients., (© 2017 by American Journal of Neuroradiology.)

Objectives: To study the predictive value of coronary calcification score (CCS) for future cardiovascular (CVS) events as detected by multi-detector computed tomography (MDCT) in patients with rheumatoid arthritis(RA) and systemic lupus erythematosus (SLE)., Methods: A total of 152 patients with RA and SLE, and 106 healthy controls underwent MDCT to measure CCS. All patients were prospectively followed up for major CVS events., Results: Compared with controls, patients with RA and SLE had a significantly higher mean CCS (42.2±154.3 vs. 1.4±13.0, p<0.01) and prevalence of CCS 1-10, CCS 11-100 and CCS>100 (all p<0.05). After a mean period of 4.3±0.6 years, major CVS events occurred in 10 patients with RA and SLE. In patients with RA and SLE, a higher major CVS events rate occurred in patients with CCS 1-10 (5.0%), CCS 11-100 (14.3%) and CCS >100 (40.0%) than those with CCS=0 (1.0%, p<0.01). Multivariate Cox regression analysis revealed that hypercholesterolemia (hazard ratio (HR) 11.2, confidence interval (CI 1.4-89.3, p=0.02) and CCS>100 (HR 11.1, CI 1.31-95.0, p=0.03) were independent predictors of combined events., Conclusions: Coronary calcification detected by MDCT independently predicts CVS events in patients with RA and SLE. Risk stratification by assessment of CCS may have an important role in patients with systemic inflammatory disease.

Objective: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established., Methods: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls., Results: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production., Conclusion: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.

Background and Aim: Our study aimed to compare the performance of faecal α(1)-antitrypsin clearance (AATC) and radiolabelled human serum albumin (HSA) scintigraphy in protein-losing enteropathy (PLE)., Methods: Patients studied by both AATC and technetium-99m ((99m)Tc)-labelled HSA scintigraphy were recruited and categorized into PLE and non-PLE groups based on clinical and laboratory findings. The performance of AATC and (99m)Tc-labelled HSA scintigraphy was evaluated using clinical diagnosis of PLE as a gold standard., Results: 29 patients were recruited and 13 patients were considered to have definite PLE (PLE group). In the PLE group, all patients had a positive HSA scinigraphy and 10 (77%) had demonstrable positive tracing in the early phase. Conversely, only 6 of them (46%) had elevated AATC level (>13 m/day). Results of (99m)Tc-labelled HSA scan (but not AATC) showed significant agreement with the clinical diagnosis (κ 0.35, p = 0.013). (99m)Tc-labelled HSA scintigraphy carried higher sensitivity (100 vs. 46%) and negative predictive value (100 vs. 63%) compared to AATC in diagnosing PLE. The correlation between the results of these two investigations was only modest (κ 0.27, p = 0.04). The area under the receiver operating characteristic curve of AATC level showed no optimal diagnostic cut-off for PLE., Conclusion: (99m)Tc-labelled HSA scintigraphy was superior to AATC in diagnosing PLE., (Copyright © 2011 S. Karger AG, Basel.)

The predisposition to and clinical phenotype of systemic lupus erythematosus, an autoimmune disease that is associated with significant morbidity and mortality, are affected by genetic and environmental factors. This article aims to examine whether Asians have worse lupus by reviewing the literature on genetic predisposition and clinical outcomes, including major organ involvement, damage score and mortality in Asian populations compared with other ethnicities. A number of lupus nephritis susceptibility genes have been identified in Asians and White patients, with further variations among different Asian populations. Meta-analysis studies on various Fcγ receptor subtypes revealed that FcγRIIIA-F158 allele, which is associated with low binding affinity to IgG1 and IgG3, predisposed to lupus nephritis in Asian patients. Asian patients were reported to have higher rates of lupus nephritis-associated autoantibodies, lupus nephritis and more active glomerulonephritis compared with White patients. Renal outcome and the level of immunosuppressant use in Asians were comparable to Afro-American Blacks in some studies. Asians were also found to have higher overall damage scores compared with Whites. The difference in mortality between Asian patients and other ethnicities in different geographical regions was found to vary depending on socioeconomic factors such as access to health care. Poverty, education level, cultural and behavioural factors are confounders to ethnicity in determining clinical outcome of systemic lupus erythematosus.

Background: Results of previous studies on the level of circulating endothelial progenitor cells (EPCs), which are involved in vascular repair, in scleroderma (SSc) patients have been controversial., Objectives: To enumerate circulating EPC subsets and to examine their relation with endothelial dysfunction, biochemical markers of endothelial injury and vascular outcome in SSc patients., Methods: Enumeration of circulating CD34+KDR+ and CD133+ KDR+EPCs was performed by flow cytometry. Endothelium-dependent vasodilation was evaluated by changes in flow-mediated dilation (FMD%) in the brachial artery. Serum level of vascular endothelial growth factor (VEGF) was measured by enzyme linked immunosorbent assay., Results: SSc patients (n=52) were found to have significantly lower CD133+KDR+EPCs (3.0 vs. 7.0/μl, p<0.001) as well as FMD% (4.8% vs. 7.8%, p<0.001) compared with age and sex-matched controls (n=52). Among patients who had no concomitant cardiovascular risk factors (n=28), CD133+KDR+ EPC level was significantly lower than controls (3.8 vs. 7.3/μl, p=0.001) and correlated modestly with FMD% (r=0.29, p=0.03). Disease duration was the only determining factor identified for circulating CD133+KDR+ EPCs (p=0.03) by logistic regression analysis. Levels of serum VEGF (p=0.92) and KDR expression were not different between patients who had early and intermediate/late disease. Circulating CD34+KDR+ EPCs was not different between SSc patients and controls and did not correlate with any clinical or biochemical parameter., Conclusions: Lower circulating CD133 +KDR+ EPC subset was found in SSc patients and correlated with impaired endothelium-dependent vasodilation in patients without cardiovascular risk factors suggesting a potential role of deficient EPC recruitment contributing to endothelial dysfunction in this disease.

Background: Impaired coronary artery reserve has previously been demonstrated in patients with systemic sclerosis (SSc). Both micro- and macrovascular factors are probably contributory to the underlying pathogenesis., Objectives: To examine the frequency of coronary atherosclerosis in a series of SSc patients by computed tomography coronary angiography (CTCA), a less invasive method than conventional coronary angiography, the current gold standard in the detection of coronary atherosclerosis, and to explore its clinical associations., Methods: Nineteen consecutive SSc patients [six with diffuse (dSSc) and 13 with limited disease (lSSc)] with disease duration of >or= 3 years were recruited. Coronary calcium score and contrast angiography were examined by CT scan. Conventional cardiovascular factors and inflammatory markers were measured and correlated with CT findings., Results: The mean+/-SD age of these patients was 52.5+/-12.5 years with median disease duration of 12.5 years. Six (31.6%) patients were found to have coronary artery calcification (calcium score 13-2008). Coronary calcium was detected in one dSSc patient but contrast angiography was not performed because of interference from an in situ implantable cardiac device. Some parts of the coronary arteries were not assessable in two patients who had ectopic cardiac rhythm. Five lSSc patients had calcified plaques causing variable coronary luminal stenosis. All patients were asymptomatic. Patients with abnormal CTCA findings were more likely to be older (p < 0.001) and were less likely to have serum anti-Scl70 antibodies (p = 0.003) than those without, after Bonferroni correction., Conclusions: Coronary atherosclerosis is not uncommon in asymptomatic SSc patients. CTCA is a convenient and non-invasive method for studying coronary atherosclerosis.

A patient with longstanding rheumatoid arthritis (RA) developed swelling in a chronically inflamed knee joint while receiving prolonged methotrexate treatment. Magnetic resonance imaging and positron-emission tomography showed soft tissue swelling with intense tracer uptake. Biopsy confirmed high-grade B-cell lymphoma. He developed complete remission with rituximab plus CEOP. The role of chronic inflammation and methotrexate in the pathogenesis of lymphoma in RA was discussed.