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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]

The objective of this study was to evaluate the patterns of clinical manifestations and their mortality in a large cohort of Chinese patients with systemic lupus erythematosus. The cumulative clinical manifestations of a large group of Chinese systemic lupus erythematosus patients who fulfilled at least four American College of Rheumatology criteria for systemic lupus erythematosus were studied. Patients were divided into distinct groups by using the K-mean cluster analysis. Clinical features, prevalence of proliferative lupus nephritis (World Health Organization class III, IV), autoantibody profile, and treatment data were compared and the standardized mortality ratios were calculated for each cluster of patients. There were 1082 patients included in the study (mean age at systemic lupus erythematosus diagnosis 30.5 years; mean systemic lupus erythematosus duration 10.3 years). Three distinct groups of patients were identified. Cluster 1 (n=347) was characterized predominantly by mucocutaneous manifestations (malar rash, discoid rash, photosensitivity, oral ulcer) and arthritis but having the lowest prevalence of serositis, hematologic manifestations (hemolytic anemia, leukopenia, and thrombocytopenia), and proliferative lupus nephritis. Patients in cluster 2 (n=409) had mainly renal and hematological manifestations but having the lowest prevalence of mucocutaneous manifestations. Pulmonary and gastrointestinal manifestations were significantly more frequent in cluster 2 than the other clusters. Cluster 3 patients (n=326) had the most heterogeneous features. Besides having a high prevalence of mucocutaneous manifestations, serositis and hematologic manifestations, renal involvement, and proliferative lupus nephritis was also most prevalent among the three clusters. Patients in cluster 2 had a much higher standardized mortality ratio [standardized mortality ratio 7.23 (6.7-7.7), p<0.001] than those in cluster 3 [standardized mortality ratio 1.27 (1.1-1.5), p=0.005] and cluster 1 [standardized mortality ratio 0.95 (0.5-1.7), p=0.86]. In conclusion, patients with systemic lupus erythematosus could be clustered into prognostically distinct patterns of clinical manifestations. [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]

Necrotizing fasciitis is an uncommon but life-threatening complication in immunocompromised hosts. We reported four patients with rheumatic diseases complicated by necrotizing fasciitis and reviewed 14 others from literature search. Most patients were on corticosteroid treatment. Septic shock, disseminated intravascular coagulopathy and acute renal deterioration were common giving rise to an overall mortality rate of 27.8%. Septic arthritis may also complicate the condition. Statistical analysis on the series showed the lack of major surgical debridement as the only risk factor associated with increased mortality (RR 7.5, 95% CI 2.1–27.3, P = 0.01). Timely debridement of necrotic tissue is important for reducing mortality. [ABSTRACT FROM AUTHOR]

Variations at the ITGAM gene, which encodes for the CD11b chain of the Mac-1 (alphaMbeta2; CD11b/CD18; complement receptor-3) integrin, is one of the strongest genetic risk factors for systemic lupus erythematosus (SLE). More specifically, a genetic variant (rs1143679) which results in an arginine to histidine substitution at position 77 in the extracellular portion of the integrin is associated with disease. It has recently been shown that this amino acid substitution results in a dysfunctional integrin, which is deficient in mediating cell adhesion to integrin ligands, phagocytosis and in addition cannot restrict inflammatory cytokine production in macrophages. In this review, we discuss immunological functions of the Mac-1 integrin and how defects in the genetic variant of Mac-1 may relate to SLE development.

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.