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Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by the over production of auto-antibodies against nuclear components. Thus, SLE patients have increased morbidity and, mortality compared to healthy individuals. Available therapies are not curative and are associated with unwanted adverse effects. During the last few years, important advances in immunology research have provided rheumatologists with new tools for designing novel therapies for treating autoimmunity. However, the complex nature of SLE has played a conflicting role, hindering breakthroughs in therapeutic development. Nonetheless, new advances about SLE pathogenesis could open a fruitful line of research. Dendritic cells (DCs) have been established as essential players in the mechanisms underlying SLE, making them attractive therapeutic targets for fine-tuning the immune system. In this review, we discuss the recent advances made in revealing the mechanisms of SLE pathogenesis, with a focus on the use of DCs as a target for therapy development.

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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple alterations affecting the normal function of immune cells, such as lymphocytes, dendritic cells (DCs) and monocytes. Although the understanding of autoimmunity has significantly increased, the breakthrough in effective therapies has been modest, making necessary the development of new therapeutic strategies. Here we propose that a new potential target for therapy is haem oxygenase-1 (HO-1), an enzyme that catalyses the degradation of the haem group into biliverdin, carbon monoxide (CO) and Fe(2+) . These products exhibit immunosuppressive and anti-inflammatory effects, which can contribute to improving tolerance during organ transplantation. Because HO-1 is highly expressed by immune cells involved in SLE pathogenesis, such as monocytes and DCs, we evaluated whether induction of HO-1 expression or the administration of CO could ameliorate disease in the FcγRIIb knockout (KO) mouse model for SLE. We found that CO administration decreased the expansion of CD11b(+) cells, prevented the decline of regulatory T cells and reduced anti-histone antibodies observed in untreated FcγRIIb KO mice. Furthermore, CO-treated animals and HO-1 induction showed less kidney damage compared with untreated mice. These data suggest that HO-1 modulation and CO administration can ameliorate autoimmunity and prevent the lupus symptoms shown by FcγRIIb KO mice, highlighting HO-1 as a potential new target for autoimmune therapy.

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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple functional alterations affecting immune cells, such as B cells, T cells, dendritic cells (DCs) and monocytes. During SLE, the immunogenicity of monocytes and DCs is significantly up-regulated, promoting the activation of self-reactive T cells. Accordingly, it is important to understand the contribution of these cells to the pathogenesis of SLE and the mechanisms responsible for their altered functionality during disease. One of the key enzymes that control monocyte and DC function is haem oxygenase-1 (HO-1), which catalyses the degradation of the haem group into biliverdin, carbon monoxide and free iron. These products possess immunosuppressive and anti-inflammatory capacities. The main goal of this work was to determine HO-1 expression in monocytes and DCs from patients with SLE and healthy controls. Hence, peripheral blood mononuclear cells were obtained from 43 patients with SLE and 30 healthy controls. CD14(+) monocytes and CD4(+) T cells were sorted by FACS and HO-1 expression was measured by RT-PCR. In addition, HO-1 protein expression was determined by FACS. HO-1 levels in monocytes were significantly reduced in patients with SLE compared with healthy controls. These results were confirmed by flow cytometry. No differences were observed in other cell types, such as DCs or CD4(+) T cells, although decreased MHC-II levels were observed in DCs from patients with SLE. In conclusion, we found a significant decrease in HO-1 expression, specifically in monocytes from patients with SLE, suggesting that an imbalance of monocyte function could be partly the result of a decrease in HO-1 expression.

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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by an excessive production of auto-antibodies against double-stranded DNA, nucleosomes, ribonucleoproteins and other nuclear components. Accumulation of self-reactive antibodies leads to immune complex deposition in blood vessels, activation of macrophages and complement, inflammation and subsequent tissue damage in several organs, such as the heart, kidneys, lungs and central nervous system. Although significant progress has been made in the past 30 years of research, no effective specific treatments are currently available. The course of this disease remains unpredictable and patients diagnosed with SLE face long-term treatments with the subsequent economic, social and health burden. From the immunological perspective, SLE is a genetic- and environment-controlled disease that involves almost every constituent of the immune system, including both innate and adaptive immunity. Therefore, several immune cell types and molecules could be susceptible for intervention and modulation to develop more effective and specific treatments. More importantly, such therapies are likely not to induce complete immunosuppression and show reduced side effects on patients. In this article we discuss recent work in the field of SLE pathogenesis with a focus on data that provide clues for therapy design and new treatments.

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Behçet's disease (BD) is a systemic inflammatory vascular disease with several clinical manifestations and geographical differences in disease expression. In Middle Eastern countries it is one of the most common causes of cerebral venous thrombosis. We report a 29-year-old female admitted for acute headache and vomiting. A magnetic resonance image showed a large thrombosis of sagital and transverse sinuses. She developed oral and genital ulcers a week later. Ophthalmologic examination revealed left anterior uveitis and ipsilateral papilledema. Multiple studies ruled out a hypercoagulability syndrome. The patient used oral contraceptives. Anticoagulant therapy was prescribed. A biopsy of a genital ulcer demonstrated diffuse lymphocytic infiltration with vasculitis. After treatment with topical and systemic corticoids, her condition improved. Venous sinus thrombosis followed by oral and genital ulcers is an unusual presentation of Behçet's disease.

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The classical manifestations of Behçet disease are mouth ana genital ulcers, cutaneous lesions ana ocular involvement. The central nervous system is affected in 5 to 59% of the cases, usually in the form of meningoencephalitis or sinus venous thrombosis. We report a 17-year-old femóle presenting with a two weeks history of progressive headache, nausea and blurred vision. An initial magnetic resonance was normal. Fifteen days later she was admitted to the hospital due to progression of visual impairment. She gave a history of oral ulcers and arthralgias. A new magnetic resonance was normal. A lumbar puncture showed a cerebrospinal fluid with a protein concentration of 14 mg/dl, a glucose concentration of 64 mg/dl, 20 fresh red blood cells and a pressure of 26 cm H(2)0. The diagnosis of a pseudotumor cerebri, secondary to Behçet disease was raised and the patient was treated with colchicine and acetazolamide. The evolution was torpid and an anterior uveitis was also found. After discharge, she continued with oral and genital ulcers and was treated with infliximab. Despite treatment, headache persists.

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Behçet’s disease (BD) is a systemic inflammatory vascular disease with several clinical manifestations and geographical differences in disease expression. In Middle Eastern countries it is one of the most common causes of cerebral venous thrombosis. We report a 29-year-old female admitted for acute headache and vomiting. A magnetic resonance image showed a large thrombosis of sagital and transverse sinuses. She developed oral and genital ulcers a week later. Ophthalmologic examination revealed left anterior uveitis and ipsilateral papilledema. Multiple studies ruled out a hypercoagulability syndrome. The patient used oral contraceptives. Anticoagulant therapy was prescribed. A biopsy of a genital ulcer demonstrated diffuse lymphocytic infiltration with vasculitis. After treatment with topical and systemic corticoids, her condition improved. Venous sinus thrombosis followed by oral and genital ulcers is an unusual presentation of Behçet’s disease.

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The classical manifestations of Behçet disease are mouth ana genital ulcers, cutaneous lesions ana ocular involvement. The central nervous system is affected in 5 to 59 percent of the cases, usually in the form of meningoencephalitis or sinus venous thrombosis. We report a 17-year-old femóle presenting with a two weeks history of progressive headache, nausea and blurred vision. An initial magnetic resonance was normal. Fifteen days later she was admitted to the hospital due to progression of visual impairment. Shegave a history of oral ulcers and arthralgias. A new magnetic resonance was normal. A lumbar puncture showed a cerebrospinal fluid with a protein concentration of 14 mg/dl, aglucose concentration of 64 mg/dl, 20fresh red blood cells and a pressure of 26 cm H(2)0. The diagnosis of a pseudotumor cerebri, secondary to Behçet disease was raised and the patient was treated with colchicine and acetazolamide. The evolution was torpid and an anterior uveitis was alsofound. After discharge, she continued with oral and genital ulcers and was treated with infliximab. Despite treatment, headache persists.

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