Etiology Of Autoimmune Diseases Research Articles

Histological and immunohistochemical comparison of major salivary glands in young and old mice

Pituitary adenylate cyclase‐activating polypeptide (PACAP) is now recognized as the multi‐functional neuropeptide in various organs. We have examined the effect of PACAP for saliva secretion. In this study, we compared the parenchymal structure and the distribution of PACAP receptor, PAC1R, in three major salivary glands; parotid (PG), submandibular (SMG), sublingual (SLG) glands of young (8 weeks old) and old (8 months old) male C57BL/6 mouse. In PG, PAC1R was localized in the striated duct. In SMG, PAC1R was detected in the tall columnar epithelial cells in granular ducts and some of the cells in the striated ducts. In SLG, PAC1R was localized in the striated duct. No apparent difference of PAC1R was detected between young and old mice glands. In SLG of old mice, granular epithelial cells are detected in the striated duct. Furthermore, massive infiltrations of CD3‐ positive or B220‐positive lymphocytes were detected in old PG and SMG. These results suggested that PACAP regulated the saliva secretion by modulating the activity of striated duct and that lymphoid infiltration in PG and SMG but not in SLM might give the useful information for the etiology of autoimmune disease of salivary gland.

Risk of Inflammatory Bowel Disease According to Self-Rated Health, Pregnancy Course, and Pregnancy Complications: A Study within the Danish National Birth Cohort

BackgroundPoor self-rated health (SRH) has been connected to immunological changes, and pregnancy complications have been suggested in the etiology of autoimmune diseases including inflammatory bowel disease (IBD). We evaluated the impact of self-rated pre-pregnancy health and pregnancy course, hyperemesis, gestational hypertension, and preeclampsia on risk of IBD.MethodsInformation was collected by questionnaires from The Danish National Birth Cohort (enrolment 1996–2002) at 16th and 30th week of pregnancy and 6 months postpartum. A total of 55,699 women were followed from childbirth until development of IBD (using validated National Hospital Discharge Register diagnoses), emigration, death, or end of follow-up, 31st of October, 2011. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusting for age and evaluating pre-pregnancy BMI, parity, alcohol and tobacco consumption, and socio-occupational status as potential confounders.ResultsRisk of IBD increased with decreasing level of self-rated pre-pregnancy health (p = 0.002) and was elevated in women with poor self-rated pregnancy course (HR, 1.61, 95% CI 1.22–2.12). Associations persisted for more than 5 years postpartum. Hyperemesis and preeclampsia were not significantly associated with risk of IBD.ConclusionsThis is the first prospective observational study to suggest that poor self-rated health – in general and in relation to pregnancy – is associated with increased risk of IBD even in the long term though results needs further confirmation. Symptoms of specific pregnancy complications were, on the other hand, not significantly associated with risk of IBD.

Immunogenicity: The Elephant in the Room for Regenerative Medicine?

Paul Fairchild speaks to Alexandra Hemsley, Assistant Commissioning Editor Paul Fairchild began his research career in Oxford, UK, where he studied for a doctorate within the Nuffield Department of Surgical Sciences, focusing on the immune response to organ allografts. After spending 5 years as a postdoctoral fellow investigating the etiology of autoimmune disease in the Department of Pathology, University of Cambridge, UK, he returned to Oxford, where he is currently a University Lecturer in Preclinical Medicine within the Sir William Dunn School of Pathology and a Fellow of Trinity College. In 2008, Fairchild founded the Oxford Stem Cell Institute (OSCI), for which he currently serves as Co-Director. As a highly interdisciplinary organization, the OSCI focuses on exploiting the properties of stem cells for the treatment of some of the most intractable chronic and degenerative diseases. It is within this context that he continues to apply his background in transplantation immunology, in order to investigate the nature of the immune response to tissues differentiated from pluripotent stem cells and to develop approaches to the induction and maintenance of immunological tolerance. In a recently published book, The Immunological Barriers to Regenerative Medicine, Fairchild explores the immunological challenges that face cell therapies and confronts some common misconceptions about the immunogenicity of pluripotent cells. Here, Fairchild speaks to Regenerative Medicine about why immunological issues cannot be ignored as stem cell science moves into the clinic.

The etiology of autoimmune diseases: the case of myasthenia gravis

Autoimmune diseases comprise a wide variety of disorders, from those that are acute and spontaneously regressive to chronic diseases. Their occurrence is the sign of a loss of tolerance to self-antigens. With few exceptions, the etiology of autoimmune diseases has not been clearly established. In all cases, it is complex, involving genetic, epigenetic, and environmental factors. In this article I will attempt to analyze the various factors that have a triggering or protecting role, with particular reference to myasthenia gravis.

Genetically Driven Target Tissue Overexpression of CD40: A Novel Mechanism in Autoimmune Disease

The CD40 gene, an important immune regulatory gene, is also expressed and functional on nonmyeloid-derived cells, many of which are targets for tissue-specific autoimmune diseases, including β cells in type 1 diabetes, intestinal epithelial cells in Crohn's disease, and thyroid follicular cells in Graves' disease (GD). Whether target tissue CD40 expression plays a role in autoimmune disease etiology has yet to be determined. In this study, we show that target tissue overexpression of CD40 plays a key role in the etiology of autoimmunity. Using a murine model of GD, we demonstrated that thyroidal CD40 overexpression augmented the production of thyroid-specific Abs, resulting in more severe experimental autoimmune GD (EAGD), whereas deletion of thyroidal CD40 suppressed disease. Using transcriptome and immune-pathway analyses, we showed that in both EAGD mouse thyroids and human primary thyrocytes, CD40 mediates this effect by activating downstream cytokines and chemokines, most notably IL-6. To translate these findings into therapy, we blocked IL-6 during EAGD induction in the setting of thyroidal CD40 overexpression and showed decreased levels of thyroid stimulating hormone receptor-stimulating Abs and frequency of disease. We conclude that target tissue overexpression of CD40 plays a key role in the etiology of organ-specific autoimmune disease.

Major histocompatibility complex class I chain related gene‐A microsatellite polymorphism shows secondary association with type 1 diabetes and celiac disease in North Indians

Microsatellite polymorphism in exon 5 of major histocompatibility complex class I chain related gene-A (MIC-A) has been implicated in the etiology of autoimmune diseases including type 1 diabetes (T1D) and celiac disease (CD). In this study on North Indian population, the MIC-A5.1 allele, carrying a premature termination codon in transmembrane region, was observed with increased frequency in T1D (29.6%, odds ratio OR = 2.1, P = 0.00017) and CD patients (40.3%, OR = 3.37, P = 1.67E-05) than in controls (16.7%). When the MIC-A5.1 association was adjusted for linkage with human leukocyte antigen (HLA)-DR3, the statistical significance of the association was abolished. This implies that the observed association of MIC-A5.1 is due to its linkage disequilibrium (D' = 0.94) with HLA-B8-DR3-DQ2 haplotype and is secondary to the overall association with DR3 positive MHC haplotypes.

Molecular mimicry in the etiology of autoimmune diseases

There are currently more than 80 different autoimmune diseases, affecting approximately 100 million people worldwide. The etiology of most autoimmune diseases is unknown. The highest incidence of these diseases is in the developed countries and they are more common in women than in men. Among the most often listed factors responsible for the onset of autoimmunity are genetic predisposition and the phenomenon known as molecular mimicry. The latter stems from a similarity between microbial antigens and antigens present in the human body (self antigens). It is believed that such homology is responsible for the production of auto-antibodies and in consequence attack of the immune system against host tissues and organs. However, the main molecular factors responsible for these diseases in most cases remain unknown. While pathogenesis of many autoimmune diseases indicates the presence of molecular mimicry, at the same time the similarities between the own and foreign structures do not always result in autoimmunity. Therefore, prediction of such crucial homology responsible for the development of autoimmune disease is extremely difficult. In this paper we present examples of autoimmune diseases such as type 1 diabetes, multiple sclerosis, reactive arthritis and the potential contribution of micro-organisms to the mechanism of molecular mimicry.

592 Evaluation of Genome-Wide Loci of Iron Metabolism in Hereditary Hemochromatosis Identifies Pcsk7 as a Predictor of Liver Cirrhosis

Background: The etiology of autoimmune diseases is multifactorial but includes a dysregulated self-tolerance and a dysfunctional communication between the sympathetic nervous system (SNS) and the immune system. Regulatory T-cells are required to induce tolerance and prevent autoimmune disease. In cirrhosis, increased SNS-activity may shift cytokineresponse towards Th2-cytokines, suppressing cellular but incrementing humoral, B-cellmediated immune response. These immune modulations, and the peripheral T-cell depletion known to occur in cirrhosis, may support development of autoimmunity. We therefore aimed to investigate whether cirrhosis confers an increased risk of autoimmune disease. Methods: We used the Danish National Patient Registry (NPR) to identify all Danish citizens diagnosed with cirrhosis in 1977-2009. For each of them we sampled five genderand agematched population controls. Competing-risks regression was used to compare the risk of rheumatoid arthritis, multiple sclerosis, or inflammatory bowel disease (identified through NPR) between cirrhosis patients and controls. Results: We included 38,394 cirrhotic patients. During 217,558 total years of follow-up 442 of them developed rheumatoid arthritis (N= 206), multiple sclerosis (N=20), or inflammatory bowel disease (N=216). In the first 10 years after cirrhosis diagnosis their risk did not exceed that of the population controls (Fig. 1), but after that their risk was markedly higher (HR >10 years after cirrhosis was diagnosed). Conclusion: Liver cirrhosis associates with an increased long-term risk for multiple sclerosis, inflammatory bowel disease and/or rheumatoid arthritis. This may indicate a general enhancement in susceptibility for autoimmune phenomena in liver cirrhosis and the underlying mechanisms should be delineated.

544 Liver Cirrhosis Increases Long-Term Risk for Autoimmunity: A Nationwide Population-Based Cohort Study

Background: The etiology of autoimmune diseases is multifactorial but includes a dysregulated self-tolerance and a dysfunctional communication between the sympathetic nervous system (SNS) and the immune system. Regulatory T-cells are required to induce tolerance and prevent autoimmune disease. In cirrhosis, increased SNS-activity may shift cytokineresponse towards Th2-cytokines, suppressing cellular but incrementing humoral, B-cellmediated immune response. These immune modulations, and the peripheral T-cell depletion known to occur in cirrhosis, may support development of autoimmunity. We therefore aimed to investigate whether cirrhosis confers an increased risk of autoimmune disease. Methods: We used the Danish National Patient Registry (NPR) to identify all Danish citizens diagnosed with cirrhosis in 1977-2009. For each of them we sampled five genderand agematched population controls. Competing-risks regression was used to compare the risk of rheumatoid arthritis, multiple sclerosis, or inflammatory bowel disease (identified through NPR) between cirrhosis patients and controls. Results: We included 38,394 cirrhotic patients. During 217,558 total years of follow-up 442 of them developed rheumatoid arthritis (N= 206), multiple sclerosis (N=20), or inflammatory bowel disease (N=216). In the first 10 years after cirrhosis diagnosis their risk did not exceed that of the population controls (Fig. 1), but after that their risk was markedly higher (HR >10 years after cirrhosis was diagnosed). Conclusion: Liver cirrhosis associates with an increased long-term risk for multiple sclerosis, inflammatory bowel disease and/or rheumatoid arthritis. This may indicate a general enhancement in susceptibility for autoimmune phenomena in liver cirrhosis and the underlying mechanisms should be delineated.

602 LACTULOSE FOR MINIMAL HEPATIC ENCEPHALOPATHY IN PATIENTS WITH EXTRAHEPATIC PORTAL VEIN OBSTRUCTION: A PILOT STUDY

© 2011, INASL 44 AUTOIMMUNE DISEASE AND NON-CIRRHOTIC PORTAL HYPERTENSION Lactulose for Minimal Hepatic Encephalopathy in Patients with Extrahepatic Portal Vein Obstruction—A Pilot Study P Sharma, A Agrawal, BC Sharma, SR Mishra, SK Sarin Department of Gastroenterology, GB Pant Hospital, New Delhi Background and Aims: Minimal hepatic encephalopathy is common in patients with extrahepatic portal vein obstruction (EHPVO). Lactulose is effective in the treatment of MHE in patients with cirrhosis. There is no study on the treatment of MHE using lactulose in patients with EHPVO. Patients and Methods: Consecutive EHPVO patients were assessed by psychometric (number connection test [NCT-A and B], digit symbol test [DST], serial dot test [SDT], line tracing test [LTT]) and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests and CFF were reassessed after 3 months. Results: Of 70 patients screened prevalence of abnormal psychometric test were NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%) and LTT (44%). Thirty patients (43%) had two or more than two abnormal psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3 months of treatment. All patients could do CFF with little training. CFF in patients with MHE (n = 30) was significantly lower than those without MHE (n = 40) (38.1 ± 2.4 vs. 41.5 ± 3.1 Hz, p = 0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose need reduction, 3 (10%) did not like its taste but continued, 2 (6%) developed abdominal bloating sensation. Conclusion: Lactulose is effective in the treatment of MHE in patients with EHPVO Conflict of Interest: None Associated HLA Alleles with Pediatric and Adult AIH in North Indian Population RW Minz*, N Kaur*, S Anand*, R Aggarwal*, B Saikia*, YK Chawla** Department of *Immunopathology, **Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh Background and Aims: Autoimmune hepatitis is an unresolving inflammation of liver characterized by presence of hypergammaglobulinemia, autoantibodies and histology showing interface hepatitis. AIH is a polygenetic disorder in which genetic risk factors affect the occurrence, clinical phenotype, severity and disease outcome. The major contributor to genetic susceptibility is the HLA region. This study aimed to find the associated HLA alleles in pediatric AIH and adult AIH. Methods: Twenty pediatric AIH patients and 35 adult AIH patients were enrolled in the study following IAHG guidelines. One hundred twenty-eight healthy controls were also included in the study. The patients and the controls were typed for HLA-DR DQ by PCR–SSP method (Innotrain, Germany). Results: HLA-DRB1*08 was found to be significantly associated with adult AIH and DRB1*03 and DRB1*04 were found to be associated with pediatric AIH. Conclusion: Like other autoimmune diseases, AIH is also associated with HLA genetic susceptibility. Presence of high susceptibility alleles leads to early manifestation of the disease i.e., in childhood age, whereas presence of other associated alleles leads to disease manifestation later in age. However, there are other genetic regions that need to be studied for genetic susceptibility for the disease. Conflict of Interest: None Clinical Profile of Patients with Liver Disease of Autoimmune Etiology R Kavitha*, TM Ramachandran**, T Varghese*** *DM Trainee and Presenting Author,**Additional Professor, ***Professor Department of Gastroenterology, Govt Medical College, Calicut, Kerala Aim: To determine the incidence, clinical, and biochemical profile of autoimmune hepatitis in a tertiary care institution. Methods: Patients presented with acute or chronic liver disease between January 2009 and January 2011 were evaluated. Data was taken retrospectively from data register. Workup included clinical, biochemical, USG, viral markers, autoimmune markers (ANA, SMA, AntiLKM, AMA, RF, p-ANCA) and liver biopsy if possible. AIH was diagnosed using Czaja criteria. Those patients who presented with features of cirrhosis were included since they were evaluated in the past with liver biopsy. 03_JCEH-Abstract.indd 44 3/18/2011 11:13:06 AM

MicroRNAs in autoimmune rheumatic diseases

The etiology of autoimmune diseases remains largely unknown. In recent years, besides genetic factors, several studies proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically epigenetic regulatory mechanisms comprise DNA methylation, a variety of histone modifications, and microRNA (miRNA) activity, all of which act upon gene and protein expression levels. In particular it is well known that epigenetic mechanisms are important for controlling the pattern of gene expression during development, the cell cycle, and the response to biological or environmental changes. In the present review a description of the most frequent epigenetic deregulations, in particular the role of miRNAs, in rheumatic autoimmune disorders will be investigated.

Etiology of autoimmune disease: past, present and future

Autoimmune disease may be defined as sustained pathology directly caused by a specific self-reactive immune response. This is opposed to the low levels of self-reactivity that are found in most chr...

Twelve-Year-Old Girl with Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic liver disease of autoimmune etiology. The initial presentation of PBC is varies from asymptomatic, abnormal liver biochemical tests to overt cirrhosis. Unlike other autoimmune liver diseases, PBC has rarely been reported in childhood. We report a case of primary biliary cirrhosis in a 12-year-old girl. In addition to characteristic histology features, strongly positive antimitochondrial antibodies, increased liver enzyme levels, increased serum quantitative immunoglobulin M levels, and cholestasis were discovered. She had been treated with ursodeoxycholic acid. In the world literature, we found only few pediatric patients of primary biliary cirrhosis. Aetiology, pathogenesis, the long-term natural history, and prognosis remain obscure. Due to increased awareness of early-onset PBC, rather than typical older ones, further pediatric cases may be discovered.

The ability of green tea to alleviate autoimmune diseases: fact or fiction?

Autoimmune diseases are a major health threat affecting 3–8% of the population in the industrialized world. While the etiology of autoimmune diseases is unclear, genetic, infectious and environmental factors are implicated. Nutrition is viewed as a modifiable environmental factor to potentially prevent and/or alleviate autoimmune diseases. Green tea consumption is suggested to have many health benefits, probably owing to its high content of polyphenols, known as catechins, among which epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active. A limited number of animal studies have demonstrated that green tea/EGCG can, to a varied degree, improve autoimmune diseases. These diseases include, ranking in order of the available information in literature, rheumatoid arthritis, inflammatory bowel disease (IBD), Sjogren’s syndrome and Type 1 diabetes (T1D; sharing the same animal model) and experimental autoimmune encephalomyelitis (EAE, murine model for human multiple sclerosis [MS]). Employing collagen- or adjuvant-induced arthritis rodent models, investigators have observed that administering green tea polyphenols (GTP, mainly EGCG) or EGCG alleviates the disease as demonstrated by reduced disease incidence, severity, pathology, serum autoantibody levels, and production or gene expression of relevant inflammation mediators/markers

Antigenic challenge in the etiology of autoimmune disease in women

Infection has long been implicated as a trigger for autoimmune disease. Other antigenic challenges include receipt of allogeneic tissue or blood resulting in immunomodulation. We investigated antigenic challenges as possible risk factors for autoimmune disease in women using the Health and Retirement Study, a nationally representative longitudinal study, linked to Medicare files, years 1991–2007. The prevalence of autoimmune disease (rheumatoid arthritis, Hashimoto’s disease, Graves’ disease, systemic lupus erythematosus, celiac disease, systemic sclerosis, Sjögren syndrome and multiple sclerosis) was 1.4% in older women (95% CI: 1.3%, 1.5%) with significant variation across regions of the United States. The risk of autoimmune disease increased by 41% (95% CI of incidence rate ratio (IRR): 1.10, 1.81) with a prior infection-related medical visit. The risk of autoimmune disease increased by 90% (95% CI of IRR: 1.36, 2.66) with a prior transfusion without infection. Parity was not associated with autoimmune disease. Women less than 65 years of age and Jewish women had significantly elevated risk of developing autoimmune disease, as did individuals with a history of heart disease or end-stage renal disease. Antigenic challenges, such as infection and allogeneic blood transfusion, are significant risk factors for the development of autoimmune disease in older women.

The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases

During recent years, researchers have been focusing on the concept of an infectious etiology of autoimmune diseases. The most discussed theory is molecular mimicry, i.e. the emergence of autoreactive clones of T- and B-lymphocytes as a result of cross-immune response to homologous bacterial or viral antigen. Information on the role of probiotic microorganisms (PM) in the molecular mechanisms of autoimmune thyroid diseases (ATD) is limited. Using proteins and immunogenic peptides databanks and relevant computer programs, the homology between the amino acid sequences of thyroid peroxidase (TPO) and thyroglobulin (Tg), which are potential B- and T-cell epitopes of these antigens, and proteins of bifidobacteria and lactobacilli was established. Moreover, we have found components of cells of Bifidobacterium bifidum 791, Bifidobacterium adolescentis 94 BIM, Bifidobacterium longum B379M and Lactobacillus plantarum B-01 that selectively bind human antibodies to TPO (anti-TPO) and antibodies to Tg (anti-Tg) and compete with natural antigens for the binding of anti-TPO and anti-Tg in ELISA. Additionally, a three-fold difference was observed between the probability of detecting antibodies (Abs) to the antigens of L. plantarum B-01 and B. bifidum 791 in serum samples containing and those not containing anti-TPO. On the whole, our data are arguments in favour of the assumption of the possible role of PM of the genera Bifidobacterium and Lactobacillus in triggering ATD by the mechanism of molecular mimicry. The data obtained in silico and in vitro should be proven by use of animal models and clinical studies for extrapolations to the whole body. Possible antigenic properties of components/proteins of bifidobacteria and lactobacilli, selectively binding anti-TPO and anti-Tg should be taken into consideration. Natural human Abs to these bacterial components are probably able to cross-react with the TPO and Tg in the ELISA for detection of anti-TPO and anti-Tg, which are serologic markers of ATD. It can lead to unspecific false positive results and, hence, to an incorrect diagnosis.

Helicobacter pylori and autoimmune diseases

Helicobacter pylori (H. pylori) is a widely prevalent microbe, with between 50 and 80% of the population infected worldwide. Clinically, infection with H. pylori is commonly associated with peptic ulcer disease, but many of those infected remain asymptomatic. H. pylori has evolved a number of means to affect the host immune response and has been implicated in many diseases mitigated by immune dysregulation, such as immune thrombocytopenic purpura (ITP), atrophic gastritis, and mucosa associated lymphoid tissue (MALT) lymphoma. Autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome, are the result of a dysregulated host immune system which targets otherwise healthy tissues. The exact etiology of autoimmune diseases is unclear, but it has long been suggested that exposure to certain environmental agents, such as viral and bacterial infection or chemical exposures, in genetically susceptible individuals may be the catalyst for the initiation of autoimmune processes. Because of its prevalence and ability to affect human immune function, many researchers have hypothesized that H. pylori might contribute to the development of autoimmune diseases. In this article, we review the available literature regarding the role of chronic H. pylori infection in various autoimmune disease states.

Clinical Profile of Patients with Liver Disease of Autoimmune Etiology

Clinical Profile of Patients with Liver Disease of Autoimmune Etiology

The epigenetics of autoimmunity

The etiology of autoimmune diseases remains largely unknown. Concordance rates in monozygotic twins are lower than 50% while genome-wide association studies propose numerous significant associations representing only a minority of patients. These lines of evidence strongly support other complementary mechanisms involved in the regulation of genes expression ultimately causing overt autoimmunity. Alterations in the post-translational modification of histones and DNA methylation are the two major epigenetic mechanisms that may potentially cause a breakdown of immune tolerance and the perpetuation of autoimmune diseases. In recent years, several studies both in clinical settings and experimental models proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically, data support the impact of epigenetic changes in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases, in some cases based on mechanistical observations. We herein discuss what we currently know and what we expect will come in the next future. Ultimately, epigenetic treatments already being used in oncology may soon prove beneficial also in autoimmune diseases.

Human plasma membrane-derived vesicles inhibit the phagocytosis of apoptotic cells – Possible role in SLE

Plasma membrane-derived vesicles (PMVs) also known as microparticles, are small membrane-bound vesicles released from the cell membrane via blebbing and shedding. PMVs have been linked with various physiological functions as well as pathological conditions such as inflammation, autoimmune disease and cardiovascular disease. PMVs are characterised by the expression of phosphatidylserine (PS) on the plasma membrane. PS, also expressed on apoptotic cells (ACs) enables macrophages to phagocytose ACs. As it is widely known that PMV production is increased during apoptosis, we were able to show that PMVs could compete dose dependently with ACs for the PS receptor on macrophages, so reducing phagocytosis of ACs. In a clinical setting this may result in secondary necrosis and further pathological conditions. In SLE in which there are raised PMV levels, there is an anti-phospholipid-mediated increase in PMV release, which can be abrogated by depletion of IgG. Our work provides an insight into how PMVs may play a role in the aetiology of autoimmune disease, in particular SLE.