Cardiovascular disease in latin american patients with systemic lupus erythematosus: a cross-sectional study and a systematic review

Objective. This study was performed to determine the prevalence of and associated risk factors for cardiovascular disease (CVD) in Latin American (LA) patients with systemic lupus erythematosus (SLE). Methods. First, a cross-sectional analytical study was conducted in 310 Colombian patients with SLE in whom CVD was assessed. Associated factors were examined by multivariate regression analyses. Second, a systematic review of the literature on CVD in SLE in LA was performed. Results. There were 133 (36.5%) Colombian SLE patients with CVD. Dyslipidemia, smoking, coffee consumption, and pleural effusion were positively associated with CVD. An independent effect of coffee consumption and cigarette on CVD was found regardless of gender and duration of disease. In the systematic review, 60 articles fulfilling the eligibility criteria were included. A wide range of CVD prevalence was found (4%–79.5%). Several studies reported ancestry, genetic factors, and polyautoimmunity as novel risk factors for such a condition.Conclusions. A high rate of CVD is observed in LA patients with SLE. Awareness of the observed risk factors should encourage preventive population strategies for CVD in patients with SLE aimed at facilitating the suppression of cigarette smoking and coffee consumption as well as at the tight control of dyslipidemia and other modifiable risk factors.

Lupus nephritis: an overview of recent findings

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) since it is the major predictor of poor prognosis. In susceptible individuals suffering of SLE, in situ formation and deposit of immune complexes (ICs) from apoptotic bodies occur in the kidneys as a result of an amplified epitope immunological response. IC glomerular deposits generate release of proinflammatory cytokines and cell adhesion molecules causing inflammation. This leads to monocytes and polymorphonuclear cells chemotaxis. Subsequent release of proteases generates endothelial injury and mesangial proliferation. Presence of ICs promotes adaptive immune response and causes dendritic cells to release type I interferon. This induces maturation and activation of infiltrating T cells, and amplification of Th2, Th1 and Th17 lymphocytes. Each of them, amplify B cells and activates macrophages to release more proinflammatory molecules, generating effector cells that cannot be modulated promoting kidney epithelial proliferation and fibrosis. Herein immunopathological findings of LN are reviewed.

Preferential binding to elk-1 by sle-associated il10 risk allele upregulates il10 expression

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans.

Lupus nephritis in colombians: Contrasts and comparisons with other populations

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) since it is the major predictor of poor prognosis. The purpose of this study was to examine the clinical and immunological characteristics associated with LN development during the course of SLE in Colombians. Therefore, patients with SLE followed at five different referral centers in Medellin, Bogota, and Cali were included in this cross-sectional and multicenter study. Factors influencing LN were assessed by conditional logistic regression analysis, adjusting by gender, age at onset, duration of disease, and city of origin. The entire sample population included 467 patients, of whom 51% presented with LN. The presence of anti-dsDNA antibodies (adjusted odds ratio (AOR), 2.06; 95% confidence interval (CI), 1.16–3.65), pleuritis (AOR, 3.82; 95% CI, 1.38–10.54), and hypertension (AOR, 2.63; 95% CI, 1.23–5.62) were positively associated with LN, whereas the presence of anti-La antibodies was a protective factor against LN development (AOR, 0.4; 95% CI, 0.19–0.85). A review of literature on LN in different populations is made. The identified clinical- and laboratory-associated factors would assist earlier diagnosis and guide decisions on therapeutic interventions on this critical and frequent complication of SLE.

MicroRNA-3148 Modulates Allelic Expression of Toll-Like Receptor 7 Variant Associated with Systemic Lupus Erythematosus

We previously reported that the G allele of rs3853839 at 3′untranslated region (UTR) of Toll-like receptor 7 (TLR7) was associated with elevated transcript expression and increased risk for systemic lupus erythematosus (SLE) in 9,274 Eastern Asians [P = 6.5×10−10, odds ratio (OR) (95%CI) = 1.27 (1.17–1.36)]. Here, we conducted trans-ancestral fine-mapping in 13,339 subjects including European Americans, African Americans, and Amerindian/Hispanics and confirmed rs3853839 as the only variant within the TLR7-TLR8 region exhibiting consistent and independent association with SLE (Pmeta = 7.5×10−11, OR = 1.24 [1.18–1.34]). The risk G allele was associated with significantly increased levels of TLR7 mRNA and protein in peripheral blood mononuclear cells (PBMCs) and elevated luciferase activity of reporter gene in transfected cells. TLR7 3′UTR sequence bearing the non-risk C allele of rs3853839 matches a predicted binding site of microRNA-3148 (miR-3148), suggesting that this microRNA may regulate TLR7 expression. Indeed, miR-3148 levels were inversely correlated with TLR7 transcript levels in PBMCs from SLE patients and controls (R2 = 0.255, P = 0.001). Overexpression of miR-3148 in HEK-293 cells led to significant dose-dependent decrease in luciferase activity for construct driven by TLR7 3′UTR segment bearing the C allele (P = 0.0003). Compared with the G-allele construct, the C-allele construct showed greater than two-fold reduction of luciferase activity in the presence of miR-3148. Reduced modulation by miR-3148 conferred slower degradation of the risk G-allele containing TLR7 transcripts, resulting in elevated levels of gene products. These data establish rs3853839 of TLR7 as a shared risk variant of SLE in 22,613 subjects of Asian, EA, AA, and Amerindian/Hispanic ancestries (Pmeta = 2.0×10−19, OR = 1.25 [1.20–1.32]), which confers allelic effect on transcript turnover via differential binding to the epigenetic factor miR-3148.

16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus

Background: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naive mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intracerebra-ventricularly (ICV) with the 16/6-Id antibody. Methods: C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id antibody or commercial human IgG antibodies (control). The mice were tested for depression by the forced swimming test (FST), locomotor and explorative activity by the staircase test, and cognitive functions were examined by the novel object recognition and Y-maze tests. Brain slices were stained for inflammatory processes. Results: 16/6-Id injected mice were cognitively impaired as shown by significant differences in the preference for a new object in the novel object recognition test compared to controls (P = 0.012). Similarly, the preference for spatial novelty in the Y-maze test was significantly higher in the control group compared to the 16/6-Id-injected mice (42% vs. 9%, respectively, P = 0.065). Depression-like behavior and locomotor activity were not significantly different between the16/6-Id-injected and the control mice. Immunohistochemistry analysis revealed an increase in astrocytes and microglial activation in the hippocampus and amygdala, in the 16/6-Id injected group compared to the control. Conclusions: Passive transfer of 16/6-Id antibodies directly into mice brain resulted in cognitive impairments and histological evidence for brain inflammation. These findings shed additional light on the diverse mosaic pathophysiology of neuropsychiatric lupus.

Anti-c1q y anti-nucleosoma en lupus eritematoso sistémico – relación con actividad

ntroducción : La mortalidad de los pacientes con Lupus eritematoso sistémico (LES) es 3 a 5 veces comparada con la población general. Detect ar oportunam ente la actividad del LES reduc e morbi - mortalidad. Las pruebas disponibles actualmente no son eficientes. Se requieren nuevos biomarcadores

El costo de la atención ambulatoria del lupus eritematoso sistémico en Colombia. Contrastes y comparaciones con otras poblaciones.

Introducción: el lupus eritematoso sistémico (LES) es considerado una enfermedad de alto costo. La expresión clínica de la enfermedad depende de la ubicación geografía y la etnicidad. El objetivo de este estudio fue el calcular los costos ambulatorios relacionado al LES en una cohorte colombiana, identificar los predictores de costos y comparar nuestro resultados con otras poblaciones. Métodos: Se realizó una aproximación de tipo prevalencia en 100 pacientes LES en quienes se evaluaron los costos directos médicos, directos no médicos, indirectos e intangibles. Todos los costos médicos fueron evaluados usando una metodología abajo hacia arriba. Los costos directos fueron valorados desde una perspectiva social usando una metodología de micro-costeo. Los costos indirectos se evaluaron mediante una aproximación de capital humano, y los costos intangibles calculados a partir de los años de vida ajustados por calidad (AVAC). Se analizaron los datos por medio de un análisis multivariado. Para comparaciones con otras poblaciones todos los costos fueron expresados como la razón entre los costos y producto interno bruto nacional per cápita. Resultados: La media de costos totales fue 13.031±9.215 USD (ajustados por el factor de conversión de paridad del poder adquisitivo), lo cual representa el 1,66 del PIB per capita de Colombia. Los costos directos son el 64% de los costos totales. Los costos médicos representan el 80% de los costos directos,. Los costos indirectos fueron el 10% y los costos intangibles el 25% de los costos totales. Los medicamentos representaron el 45% de los costos directos. Mayores costos se relacionaron con el estrato socioeconómico, seguro médico privado, AVAC, alopecia, micofenolato mofetilo, y terapia anticoagulante. Los costos directos ajustados de los pacientes con LES en Colombia fueron mayores que en Norte América y en Europa. Conclusiones: el LES impone una carga económica importante para la sociedad. Los costos relacionados con la atención médica y AVAC fueron los principales contribuyentes al alto costo de la enfermedad. Estos resultados pueden ser referencia para determinar políticas en salud pública así como comparar el gasto en salud de forma internacional.

Towards a single crystal Raman spectrum of kaolinite at 77 K

The Raman spectra at 77 K of the hydroxyl stretching of kaolinite were obtained along the three axes perpendicular to the crystal faces. Raman bands were observed at 3616, 3658 and 3677 cm−1 together with a distinct band observed at 3691 cm−1 and a broad profile between 3695 and 3715 cm−1. The band at 3616 cm−1 is assigned to the inner hydroxyl. The bands at 3658 and 3677 cm−1 are attributed to the out-of-phase vibrations of the inner surface hydroxyls. The Raman spectra of the in-phase vibrations of the inner-surface hydroxyl-stretching region are described in terms of transverse and longitudinal optic splitting. The band at 3691 cm−1 is assigned to the transverse optic and the broad profile to the longitudinal optic mode. This splitting remained even at liquid nitrogen temperature. The transverse optic vibration may be curve resolved into two or three bands, which are attributed to different types of hydroxyl groups in the kaolinite.

Queensland Environmental Practice Reporter 17(77) (2011/2012) Editorial

This issue begins with a paper by QUT masters student, Jenny Kortlaender, which considers the effectiveness of the United Nations Convention on Biological Diversity in addressing global biodiversity decline. This is followed by a paper by Fiona Leddy which critically analyses international shipping in Australian waters and the approach taken by Australia laws in addressing the risks posed by ship-based oil pollution. The third paper in this issue is by Adjunct Professor Hugh Lavery, Gina Lee and Carolyn S. Sandercoe. This paper considers the ecological principles to be followed in the sustainable design of large-scale marina developments. This paper highlights the differences between the practice of landscape ecology and the design of ecological landscapes. Finally, this issue includes a summary of relevant cases from the Queensland Planning and Environment Court and Court of Appeal by Michael Walton and Ben Job.

Clergy Sexual Abuse Litigation: Survivors Seeking Justice By Jennifer M. Balboni (Boulder: First Forum Press, 2011, 180pp. £43.77)

Balboni identifies her interest as being the processes of official disclosure and the path taken to civil litigation by survivors of child sexual abuse by Roman Catholic Clergy. The empirical data, on which this work is based, come in the form of in-depth face-to-face interviews with 22 survivors of clergy sexual abuse who have pursued litigation and 13 of their advocates. Balboni provides a space for survivors’ accounts of the ‘why’ behind their decision making and the impact of civil litigation on their lives to be heard, discussed and contextualized with both clarity and sensitivity. She acknowledges the breadth and depth of survivor responses, and the perspectives of their legal advocates, employing defiance theory, symbolic interaction and other points of analysis, to capture the journey of survivors towards litigation and beyond. Balboni’s work is deeply poignant in its recognition of survivors’ voices, the complex transformative capacity of litigation, the effects of community forming amongst survivors and the complex nature of ‘empowerment’ obtained by survivors through civil litigation. Acknowledging that, for many survivors, litigation becomes a means of identity change and truth telling, Balboni admits that ‘these survivors helped me understand that litigation is more about voice than monetary settlement’ (p. 149). This work is not deeply analytical or theoretically rich but privileges the voices of survivors and their advocates with sufficient frameworks to contextualize and explain participants’ perspectives and experiences.