Lupus

Hội chứng antiphospholipid (APS) được định nghĩa bởi sự hiện diện của huyết khối và/hoặc các vấn đề liên quan đến thai kỳ kết hợp với sự hiện diện liên tục của các kháng thể antiphospholipid trong lưu thông: kháng đông lupus, kháng thể chống cardiolipin và/hoặc kháng thể chống β2-glycoprotein I với nồng độ từ trung bình đến cao. Quản lý tình trạng huyết khối ở bệnh nhân APS là một chủ đề gây tranh cãi. Tập hợp các khuyến nghị này là kết quả của nỗ lực xây dựng hướng dẫn điều trị trong một nhóm bác sĩ chuyên khoa về Tim mạch, Thần kinh, Huyết học, Thấp khớp và Nội khoa, với trọng tâm là lâm sàng và nghiên cứu về APS.

The objective was to investigate the relation between serum levels of interferon-α (IFN-α), the activity of an endogenous IFN-a inducing factor (SLE-IIF), clinical and immunological disease activity as well as serum levels of antiretroviral antibodies in SLE. Serum levels of IFN-α were measured in serial sera from 30 patients sampled at different stages of disease activity (SLEDAI score). The SLE-IIF activity was measured by its ability to induce IFN-α production in cultures of normal peripheral blood mononuclear cells. Both serum IFN-α and SLE-IIF increased markedly at flare in serially followed patients. The SLEDAI score, levels of anti-dsDNA antibodies and IL-10 correlated positively, and complement components Clq, C3 and leukocytes correlated inversely with serum concentrations of IFN-α. The extent of multiple organ involvement correlated with serum IFN-α. No relation between concentrations of retroviral peptide binding antibodies and IFN-α or SLE-IIF activity was found. The close relationship between disease activity in SLE patients and IFN-α serum levels suggests that activation of the type I IFN system might be of importance in the disease process.

MicroRNAs (miRNAs) are noncoding RNA molecules of 21—24 nt that regulate the expression of target genes in a post-transcriptional manner. Evidence indicates that miRNAs play essential roles in embryogenesis, cell differentiation and pathogenesis of human diseases. This study describes a comparison between the miRNA profile of the systemic lupus erythematosus (SLE) patients and the controls to develop further understanding of the pathogenesis of SLE. Peripheral blood mononuclear cells were isolated from blood samples of 23 SLE patients, 10 idiopathic thrombocytopenic purpura patients and 10 healthy controls. The miRNA microarray chip analysis identified 16 miRNAs differentially expressed in SLE. The chip results were confirmed by northern blot analysis. This work indicates that miRNAs are potential diagnosis biomarkers and probable factors involved in the pathogenesis of SLE. Lupus (2007) 16, 936—946.

Multiple reliable and valid disease activities indices exist and have been used successfully in longitudinal studies. However, the definition of flare, using these intruments, has not been universally decided or accepted. Because flare is one of the three major patterns of lupus activity, it will remain an important outcome measure in both longitudinal and clinical trial studies.

Systemic lupus erythematosus (SLE) is a prototypic multisystem autoimmune disorder where interplay of environmental and genetic risk factors leads to progressive loss of tolerance to nuclear antigens over time, finally culminating in clinical disease. The heterogeneity of clinical manifestations and the disease’s unpredictable course characterized by flares and remissions are very likely a reflection of heterogeneity at the origin of disease, with a final common pathway leading to loss of tolerance to nuclear antigens. Impaired clearance of immune complexes and apoptotic material and production of autoantibodies have long been recognized as major pathogenic events in this disease. Over the past decade the type I interferon cytokine family has been postulated to play a central role in SLE pathogenesis, by promoting feedback loops progressively disrupting peripheral immune tolerance and driving disease activity. The identification of key molecules involved in the pathogenesis of SLE will not only improve our understanding of this complex disease, but also help to identify novel targets for biological intervention. Lupus (2010) 19, 1012—1019.

Patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL) are at a greater risk for venous thromboembolism (VTE) than SLE patients without these antibodies. For patients without SLE there is a controversy about the risk associated with these antibodies and about their prognostic significance. We reviewed the degree of evidence and describe the odds ratio for VTE associated with aPL, namely the lupus anticoagulant (LA) and anticardiolipin antibodies (aCL), in patients without SLE. The study was a meta-analysis of seven observational studies of risk for antiphospholipid associated venous thromboembolism (VTE), excluding SLE patients. The strategies to identify published research included a computerized literature search and the review of citations in primarily relevant articles for the period 1983 to 1997. A summary of study characteristics and a critical appraisal of study quality were done. Summary odds ratios were obtained conducted using a random and a fixed effects-model. The overall odds ratio for aCL associated VTE obtained by fixed-effects model was 1.56 (95% CI, 1.10—2.24) and 1.64 (95% CI, 0.93—2.89) by random-effects model. The heterogeneity of these results appeared to be due in part to the detection limit of the aCL assay: the odds ratio was 3.21 (95% CI, 1.11—9.28) with both models when high titres only were considered. The overall odds ratio for LA associated VTE was 11.1 (95% CI, 3.81—32.3). In conclusion meta-analysis of the risk for antiphospholipid associated thrombosis demonstrated a higher risk in patients with the LA than in other patients. This risk was also higher than in patients with aCL even when high titres only were considered.

Mục tiêu: Chúng tôi nhằm xác định tác động của liệu pháp hydroxychloroquine lên mức độ các chỉ số proinflammatory/prothrombotic và điểm số hoạt động bệnh lý ở bệnh nhân lupus ban đỏ hệ thống (SLE) trong một nhóm đa sắc tộc, đa trung tâm (LUMINA). Phương pháp: Các mẫu huyết tương/huyết thanh từ bệnh nhân SLE (n = 35) được đánh giá tại thời điểm xuất phát và sau khi điều trị bằng hydroxychloroquine. Hoạt động bệnh lý được đánh giá bằng điểm SLAM-R. Mức độ của interferon (IFN)-α2, interleukin (IL)-1β, IL-6, IL-8, protein cảm ứng (IP)-10, protein hóa học tế bào đơn nhân-1, yếu tố hoại tử khối u (TNF)-α và ligand CD40 hòa tan (sCD40L) đã được xác định bằng phương pháp xét nghiệm miễn dịch đa lớp. Các kháng thể anticardiolipin được đánh giá bằng các xét nghiệm ELISA. Ba mươi hai mẫu huyết tương/huyết thanh tương ứng với tần suất từ các người hiến tặng khỏe mạnh được sử dụng làm đối chứng. Kết quả: Mức độ IL-6, IP-10, sCD40L, IFN-α và TNF-α tăng đáng kể ở bệnh nhân SLE so với đối chứng. Có một mối tương quan dương tính nhưng vừa phải giữa điểm SLAM-R tại thời điểm xuất phát và mức độ IFN-α (p = 0.0546). Liệu pháp hydroxychloroquine dẫn đến sự giảm đáng kể trong điểm SLAM-R (p = 0.0157), và sự giảm điểm SLAM-R sau liệu pháp hydroxychloroquine tương quan mạnh mẽ với sự giảm mức độ IFN-α (p = 0.0087). Kết luận: Liệu pháp hydroxychloroquine dẫn đến cải thiện lâm sàng đáng kể ở bệnh nhân SLE, điều này tương quan mạnh mẽ với việc giảm mức độ IFN-α. Điều này chỉ ra vai trò quan trọng của việc ức chế kích hoạt TLR nội sinh trong cơ chế tác động của hydroxychloroquine trên SLE và cung cấp bằng chứng bổ sung cho tầm quan trọng của interferon loại I trong sinh lý bệnh của SLE. Nghiên cứu này nhấn mạnh việc sử dụng hydroxychloroquine trong điều trị SLE.

Although males with systemic lupus erythematosus (SLE) represent 4—22% of all SLE patients, it may not be appropriate that these cases should be subordinated to females with SLE in terms of most health-related issues. Over the past few decades, some distinctive features of male lupus have been observed with regard to genetic and environmental aspects of sex differences, clinical features, and outcome. In addition, recent insights into sex disparities in this disease have brought forth a few plausible and novel pathogenetic hypotheses. This review discusses these findings and sex disparities in SLE that appear to be especially noteworthy and pertinent to our understanding of male SLE. Lupus (2010) 19, 119—129.

Objective. To examine the potential immunologic mechanism and involvement of antiphos pholipid antibodies in the pathogenesis of heart valve lesions in patients with the antiphos pholipid syndrome (APS).

Methods. Immunoperoxidase and immunofluorescence staining methods were used to evaluate 13 heart valve specimens derived from eight patients with the APS, either primary or secondary to systemic lupus erythematosus. Primary antibodies to human immuno globulins, complement components, serum albumin and a monoclonal anti-idiotypic anti body to human anticardiolipin antibodies (aCL) were employed. Various tissue specimens from a patient with the APS as well as deformed and normal valves from subjects without the APS were used as controls.

Results. Linear subendothelial deposition consisting of immunoglobulins with complement components but not of a non-specific serum protein was found in deformed valves from patients with the APS. None of the control valves or tissues disclosed similar deposition. The same pattern and location of staining was obtained by the anti-idiotypic antibody to aCL. A significant amount of IgG immunoglobulins that bound to cardiolipin was eluted from a valve of a patient with secondary APS.

Conclusion. Deposits of immunoglobulins including aCL, and of complement components, are common in affected valves of patients with primary and secondary APS. Such deposits may be involved in the pathogenesis of valvular lesions.