Search

Recent research in systemic lupus erythematosus (SLE) yielded new antigens and antibodies in SLE patients. We describe the various autoantibodies that can be detected in patients with SLE. A literature review, using the terms “autoantibody” and “systemic lupus erythematosus”, was conducted to search for articles on autoantibodies in SLE, their target antigens, association with disease activity and other clinical manifestations. One hundred and eighty autoantibodies were so far described in SLE patients. These include autoantibodies that target nuclear antigens, cytoplasmic antigens, cell membrane antigens, phospholipid-associated antigens, blood cells, endothelial cells, and nervous system antigens, plasma proteins, matrix proteins, and miscellaneous antigens. The target of an autoantibody, the autoantigen properties, autoantibody frequencies in SLE, as well as clinical associations, and correlation with disease activity are described for all 180 autoantibodies. SLE is so far the autoimmune disease with the largest number of detectable autoantibodies. Their production could be antigen-driven, the result of a polyclonal B cell activation, impaired apoptotic pathways, or the outcome of an idiotypic network dysregulation.

The purpose of this study was to determine patients' survival after undergoing an early or delayed operation. We retrospectively assessed 1849 files of patients operated for proximal femoral fracture, divided into two diagnostic groups: intracapsular (n = 640) and extracapsular (n = 1209). 1163 (63%) were treated within 48 h from hospital admission and 686 (37%) were treated >48 h afterwards. Delayed operation in patients with intracapsular fractures was associated with a 1.8-fold excess risk for 1-year mortality (HR = 1.83, P = 0.008), while no effect was observed for patients with extracapsular fractures. Males had a higher HR for mortality in both diagnostic groups. Early surgical intervention is beneficial for intra-capsular femoral fractures; male gender and a high ASA score are associated with an increased mortality hazard risk.

Pemphigus and bullous pemphigoid are two autoimmune diseases that have a similar pathogenesis. Both have a genetic predisposition which promotes the production of auto-antibodies targeted against different components of the epidermal desmosome and hemidesmosome. Environmental factors play an important role in the pathogenesis of this autoimmune disease. Among these, the role of infectious agents was debated as a causative factor. We sought to determine a possible connection between various infectious agents and autoimmune bullous disease (ABD). A cohort of 148 serum samples of patients with pemphigus, bullous pemphigoid and controls was screened for evidence of a prior infection with HBV, HCV, EBV, CMV, Helicobacter pylori, Toxoplasma gondii and Treponema pallidum, utilizing the Bio-Rad BioPlex 2200 system as well as ELISA assays to complete the panel. HBV, HCV, H. pylori, T. gondii and CMV were demonstrated to have significantly higher prevalence of antibodies in patients with pemphigus and bullous pemphigoid in comparison to controls. Among them, we found a novel association between H. pylori and ABD. Our study suggests a contributing role for HBV, HCV, H. pylori, T. gondii and CMV in inducing ABD in the genetically susceptible host.

The antiphospholipid syndrome (APS) is the most common acquired thrombophilia. It is characterized by venous and arterial thrombosis, recurrent pregnancy loss, and various other clinical manifestations in the presence of antiphospholipid antibodies (aPL). Like other autoimmune diseases, the etiology of APS derives from a combination of genetic and environmental factors. The most significant environmental factors in APS are infectious agents, followed by trauma and drugs. Infections can induce aPL and, in the catastrophic variant of APS, about one-third of cases are associated with a clear recent infection. On their formation, aPL have been clearly shown to be pathogenic, because they influence all arms of the coagulation system and because passive transfer and active immunization protocols have demonstrated. Therefore, in a genetically susceptible individual, exposure to one or more infectious agent can cause a molecular mimicry and result in the production of pathogenic aPL that can induce thrombosis and pregnancy loss. Identification of the epitopes within the beta-2-glycoprotein-I molecule that serves as the target for autoantibodies makes them the target for immunomodulation of the syndrome.

Recently, considerable data have accumulated concerning the role of the immune system in atherosclerosis (AS). Several immunomodulating strategies are being evaluated that might influence the process of AS including immunosuppressive therapy, immunization (vaccination) and induction of immune tolerance. This article reviews experimental studies using the induction of immune tolerance for the suppression of respective immune responses in animal models of AS. Induction of neonatal tolerance or mucosal tolerance using autoantigens involved in atherogenesis, such as heat shock protein-65 or beta2-glycoprotein I, could modify the course of AS in animal models. These observations are of considerable interest and need further evaluation in humans.

The 10th International Congress on Antiphospholipid Antibodies (Sicily, Italy, September 29–October 3, 2002) (Fig. 1) provided enlightening aspects on the recent developments in antiphospholipid syndrome (APS) and antiphospholipid antibodies in more than 150 lectures and posters. Researchers from all aspects of medicine attended the meeting, implicating the systemic characteristics of APS. The important breakthroughs are summarized.

Antiphospholipid antibodies are the hallmark of the antiphospholipid syndrome which is characterized by thrombosis. There are currently data supporting an association between these autoantibodies and atherosclerosis as well. Human studies suggest that anti-cardiolipin and anti-beta2-glycoprotein-I antibodies are elevated in patients having coronary artery disease compared with controls. Anti-cardiolipin antibodies are also associated with typical chest pain, significant coronary artery stenosis on angiography and prediction of myocardial infarction. Laboratory studies and murine models support the pro-atherogenic role of these autoantibodies, as they are involved in uptake of oxidized LDL into macrophages, and immunization of mice with them results in enhanced atherosclerosis. There is some evidence that high anti-beta2-glycoprotein-I antibodies can present a risk factor for atherosclerosis, but more epidemiological data are required in order to confirm whether the pro-atherogenic properties of anti-phospholipid antibodies signifies an independent risk factor for atherosclerosis and its complications.

In recent years, it has become clear that the immune system has a major role in atherosclerosis development and progression. More specifically, atherosclerosis fulfills all four criteria to define a condition as being an autoimmune in nature. This association also suggests that modification of the immune response in atherosclerosis could affect this process. In this review, we summarize different aspects of immunomodulation in atherosclerosis. These include immunosuppression, active immunization, induction of tolerance, administration of intravenous immunoglobulin, gene therapy, cytokine network manipulation and statins.

Background: Intravenous immunoglobulin (IVIg) is a standard therapeutic modality for a few autoimmune diseases, such as immune thrombocytopenic purpura. However, in other hematologic autoimmune conditions its role is still controversial. Methods: Seven patients with either autoimmune hemolytic anemia, Evans’ syndrome, aplastic anemia, pure red cell aplasia, thrombotic thrombocytopenic purpura, or acquired factor VIII inhibitors were treated with a single course of high-dose (2 g/kg) IVIg. Results: A good response was observed in all seven patients, except the one with thrombotic thrombocytopenic purpura, and there were no adverse effects related to IVIg use. The literature reports on IVIg therapy in these conditions and the mechanisms of action of IVIg in autoimmune diseases are discussed. Conclusions: IVIg might be a useful agent in the treatment of several hematologic disorders other than immune thrombocytopenic purpura. Future aims of clinical research in this respect would be to identify the patient subgroups that might benefit more from IVIg in these conditions.

Objectives: To determine whether malignant thymoma is associated with high rates of concomitantly occurring autoimmune diseases. Methods: Sheba Medical Center computer records from 1966 to 1995 werereviewed to identify patients with malignant thymoma, either type I (invasive thymoma) or type II (thymic carcinoma). All patients who had malignant thymoma and autoimmune phenomena were analyzed. The diagnosis of thymic neoplasm was confirmed by two independent pathologists. The diagnosis of autoimmune diseases was based on both clinical and serological findings. Results: Six of 22 (27%) cases of malignant thymoma had an autoimmunedisease. Five patients had type I malignant thymoma and either myasthenia gravis (four patients) or Graves' disease (one patient). Only one patient had type II malignant thymoma with Sjbgren's syndrome. The diagnosis of autoimmune disease preceded the diagnosis of thymic neoplasm in four cases, and was diagnosed simultaneously in two. Conclusions: Malignant thymomas are highly associated with autoimmunediseases, as are benign thymomas. To our knowledge, we report the first documented cases of a patient with thymic carcinoma and Sjogren's syndrome, and another with invasive thymoma and Graves' disease.

The European Atherosclerosis Society Workshop on the Immune System in Atherosclerosis was held at the Hotel Intercontinental, Geneva, Switzerland, from 8–11 March 2001.

Two children were admitted to the Emergency Department (ED) after ingesting a large amount of fruit of a plant identified as Jatropha multifida. They were mildly obtunded, had intractable vomiting, and seemed dehydrated. Intravenous fluid replacement and urine alkalinization were initiated. After stabilization, their 5-day hospital stays were uneventful except for a subclinical rise of liver enzymes. Jatropha species contain the toxalbumin ricin, which causes severe vomiting and diarrhea, dehydration, shock, and renal and hepatic impairment. Ricin also has cardiotoxic and hemolytic effects and several deaths have been documented. Children are attracted by the shape and the color of the Jatropha fruits. Mortality can be prevented by immediate fluid and electrolyte replacement.

The 3rd International Congress on Autoimmunity was held at the Palexpo Congress Center, Geneva, Switzerland, from 20–24 February 2002.