Sample records for putative autoimmune autonomic

  1. Impaired autonomic responses to emotional stimuli in autoimmune limbic encephalitis

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    Olga eSchröder


    Full Text Available Limbic encephalitis (LE is an autoimmune-mediated disorder that affects structures of the limbic system, in particular the amygdala. The amygdala constitutes a brain area substantial for processing of emotional, especially fear-related signals. The amygdala is also involved in neuroendocrine and autonomic functions, including skin conductance responses (SCRs to emotionally arousing stimuli. This study investigates behavioral and autonomic responses to discrete emotion-evoking and neutral film clips in a patient suffering from LE associated with contactin-associated protein-2 (CASPR2-antibodies as compared to a healthy control group. Results show a lack of SCRs in the patient while watching the film clips, with significant differences compared to healthy controls in the case of fear-inducing videos. There was no comparable impairment in behavioral data (emotion report, valence and arousal ratings. The results point to a defective modulation of sympathetic responses during emotional stimulation in patients with LE, probably due to impaired functioning of the amygdala.

  2. Cardiac autonomic imbalance by social stress in rodents: understanding putative biomarkers

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    Susan K Wood, Phd


    Full Text Available Exposure to stress or traumatic events can lead to the development of depression and anxiety disorders. In addition to the debilitating consequences on mental health, patients with psychiatric disorders also suffer from autonomic imbalance, making them susceptible to a variety of medical disorders. Emerging evidence utilizing spectral analysis of heart rate variability (HRV, a reliable noninvasive measure of cardiovascular autonomic regulation, indicates that patients with depression and various anxiety disorders (i.e., panic, social, generalized anxiety disorders, and post traumatic stress disorder are characterized by decreased HRV. Social stressors in rodents are ethologically relevant experimental stressors that recapitulate many of the dysfunctional behavioral and physiological changes that occur in psychological disorders. In this review, evidence from clinical studies and preclinical stress models identify putative biomarkers capable of precipitating the comorbidity between disorders of the mind and autonomic dysfunction. Specifically, the role of corticotropin releasing factor, neuropeptide Y and inflammation are investigated. The impetus for this review is to highlight stress-related biomarkers that may prove critical in the development of autonomic imbalance in stress -related psychiatric disorders.

  3. A Japanese case of autoimmune autonomic ganglionopathy (AAG) and a review of AAG cases in Japan. (United States)

    Hayashi, Michiyuki; Ishii, Yuko


    A 29-year-old woman presented with acute, pure autonomic (both sympathetic and parasympathetic) failure and positive antibody to ganglionic nicotinic acetylcholine receptor; the diagnosis was autoimmune autonomic ganglionopathy (AAG). She had typical symptoms of AAG, although the patient also had coughing episodes and psychiatric symptoms, which are not typical of AAG in Western countries but are common in AAG cases in Japan. In a review of the Japanese literature, 29 cases of AAG had been reported. AAG patients in Japan were younger and more male predominant than in Western countries. Of the patients in these 29 cases, 10 (34.5%) had coughing episodes and 12 (41.4%) had psychiatric symptoms.

  4. Coexistent Autoimmune Autonomic Ganglionopathy and Myasthenia Gravis Associated with Non-Small Cell Lung Cancer (United States)

    Peltier, Amanda C.; Black, Bonnie K.; Raj, Satish R.; Donofrio, Peter; Robertson, David; Biaggioni, Italo


    We report a case of a 55 year old man with non-small cell lung cancer who underwent radiation, chemotherapy with carbotaxol and paclitaxel, and left upper lobe removal two years prior to evaluation. He was referred for disabling orthostatic hypotension (113/69 supine, 66/47 mmHg standing after 10 minutes without a compensatory heart rate increase (57 to 59 bpm), fatigue, and constipation with episodes of ileus. Clinical examination showed mild ptosis bilaterally, fatiguable neck flexor weakness and hip flexor weakness. Blood pressure response to Valsalva maneuver was abnormal with absence of phase 4 overshoot and a Valsalva heart rate ratio of 1.04, The plasma norepinephrine level was low (79 pg/ml supine to 330 pg/ml standing). Single fiber EMG of the right extensor digitorum communis revealed normal mean MCD (jitter) but several pairs exceeded a jitter of 100 µs. Antibodies against muscle acetylcholine receptor [(AChR) 0.66 nmol/L, normal <0.02] and ganglionic AChR (0.34 nmol/L, normal <0.02) were present. Treatment with plasma exchange normalized responses to standing posture (105/68 supine to 118/82 mmHg standing, 66 to 79 bpm), to Valsalva (normal blood pressure overshoot, HR ratio 1.47), norepinephrine (194 pg/ml supine, 763 standing), and jitter measurements. We conclude that autoimmune autonomic ganglionopathy and myasthenia gravis can coexist and suggest that the latter should be excluded in patients with autoimmune autonomic ganglionopathy who complain of fatigue that is improved with non-supine rest. PMID:19882640

  5. A putative autonomous 20.5 kb-CACTA transposon insertion in an F3'H allele identifies a new CACTA transposon subfamily in Glycine max

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    Vodkin Lila


    Full Text Available Abstract Background The molecular organization of very few genetically defined CACTA transposon systems have been characterized thoroughly as those of Spm/En in maize, Tam1 of Antirrhinum majus Candystripe1 (Cs1 from Sorghum bicolor and CAC1 from Arabidopsis thaliana, for example. To date, only defective deletion derivatives of CACTA elements have been described for soybean, an economically important plant species whose genome sequence will be completed in 2008. Results We identified a 20.5 kb insertion in a soybean flavonoid 3'-hydroxylase (F3'H gene representing the t* allele (stable gray trichome color whose origin traces to a single mutable chimeric plant displaying both tawny and gray trichomes. This 20.5 kb insertion has the molecular structure of a putative autonomous transposon of the CACTA family, designated Tgmt*. It encodes a large gene that was expressed in two sister isolines (T* and tm of the stable gray line (t* from which Tgmt* was isolated. RT-PCR derived cDNAs uncovered the structure of a large precursor mRNA as well as alternatively spliced transcripts reminiscent of the TNPA-mRNA generated by the En-1 element of maize but without sequence similarity to the maize TNPA. The larger mRNA encodes a transposase with a tnp2 and TNP1-transposase family domains. Because the two soybean lines expressing Tgmt* were derived from the same mutable chimeric plant that created the stable gray trichome t* allele line from which the element was isolated, Tgmt* has the potential to be an autonomous element that was rapidly inactivated in the stable gray trichome t* line. Comparison of Tgmt* to previously described Tgm elements demonstrated that two subtypes of CACTA transposon families exist in soybean based on divergence of their characteristic subterminal repeated motifs and their transposases. In addition, we report the sequence and annotation of a BAC clone containing the F3'H gene (T locus which was interrupted by the novel Tgmt* element

  6. Thyroid autoimmunity

    NARCIS (Netherlands)

    Wiersinga, Wilmar M.


    Autoimmune thyroid disease (AITD) is a multifactorial disease in which autoimmunity against thyroid antigens develops against a particular genetic background facilitated by exposure to environmental factors. Immunogenicity of the major thyroid antigens thyroid peroxidase, thyroglobulin (TG) and

  7. Autoimmune gastritis. (United States)

    Kulnigg-Dabsch, Stefanie


    Autoimmune gastritis is a chronic inflammatory disease with destruction of parietal cells of the corpus and fundus of the stomach. The known consequence is vitamin B12 deficiency and, consequently, pernicious anemia. However, loss of parietal cells reduces secretion of gastric acid which is also required for absorption of inorganic iron; thus, iron deficiency is commonly found in patients with autoimmune gastritis. This usually precedes vitamin B12 deficiency and is found mainly in young women. Patients with chronic iron deficiency, especially those refractory to oral iron therapy, should therefore be evaluated for the presence of autoimmune gastritis.

  8. Autoimmune disorders (United States)

    ... exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  9. Autoimmune pancreatitis

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    Davorin Dajčman


    Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and

  10. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus


    during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either...

  11. Autoimmune hepatitis. (United States)

    Vergani, D; Mieli-Vergani, G


    Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.

  12. Psychoneuroimmunology - psyche and autoimmunity. (United States)

    Ziemssen, Tjalf


    Psychoneuroimmunology is a relatively young field of research that investigates interactions between central nervous and immune system. The brain modulates the immune system by the endocrine and autonomic nervous system. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and autoimmune disease. For several diseases, the relevance of psychoneuroimmunological findings has already been demonstrated.


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    Yusri Dianne Jurnalis


    Full Text Available AbstrakHepatitis autoimun merupakan penyakit inflamasi hati yang berat dengan penyebab pasti yang tidak diketahui yang mengakibatkan morbiditas dan mortalitas yang tinggi. Semua usia dan jenis kelamin dapat dikenai dengan insiden tertinggi pada anak perempuan usia prepubertas, meskipun dapat didiagnosis pada usia 6 bulan. Hepatitis autoimun dapat diklasifikasikan menjadi 2 bagian berdasarkan adanya antibodi spesifik: Smooth Muscle Antibody (SMA dengan anti-actin specificity dan/atau Anti Nuclear Antibody (ANA pada tipe 1 dan Liver-Kidney Microsome antibody (LKM1 dan/atau anti-liver cytosol pada tipe 2. Gambaran histologisnya berupa “interface hepatitis”, dengan infiltrasi sel mononuklear pada saluran portal, berbagai tingkat nekrosis, dan fibrosis yang progresf. Penyakit berjalan secara kronik tetapi keadaan yang berat biasanya menjadi sirosis dan gagal hati.Tipe onset yang paling sering sama dengan hepatitis virus akut dengan gagal hati akut pada beberapa pasien; sekitar sepertiga pasien dengan onset tersembunyi dengan kelemahan dan ikterik progresif ketika 10-15% asimptomatik dan mendadak ditemukan hepatomegali dan/atau peningkatan kadar aminotransferase serum. Adanya predominasi perempuan pada kedua tipe. Pasien LKM1 positif menunjukkan keadaan lebih akut, pada usia yang lebih muda, dan biasanya dengan defisiensi Immunoglobulin A (IgA, dengan durasi gejala sebelum diagnosis, tanda klinis, riwayat penyakit autoimun pada keluarga, adanya kaitan dengan gangguan autoimun, respon pengobatan dan prognosis jangka panjang sama pada kedua tipe.Kortikosteroid yang digunakan secara tunggal atau kombinasi azathioprine merupakan terapi pilihan yang dapat menimbulkan remisi pada lebih dari 90% kasus. Strategi terapi alternatif adalah cyclosporine. Penurunan imunosupresi dikaitkan dengan tingginya relap. Transplantasi hati dianjurkan pada penyakit hati dekom-pensata yang tidak respon dengan pengobatan medis lainnya.Kata kunci : hepatitis Autoimmune

  14. [Autoimmune hepatitis]. (United States)

    Färkkilä, Martti


    Autoimmune hepatitis is chronic liver disease with two subtypes, type 1 with anti nuclear or smooth muscle antibodies and type 2 with LKM1 or LC1 antibodies, and both with hypergammaglobulinemia and typical histology. Prevalence of AIH is between 10 to 17 per 100000 in Europe. Up to 20-40 % of cases present with acute hepatitis. Budesonide can be used as a first line induction therapy in non-cirrhotic patients, and tiopurines, mercaptopurine or mycophenolic acid as maintenance therapies. Patients not responding to conventional therapy can be treated with ciclosporin, tacrolimus or rituximab or finally with liver transplantation.

  15. Autoimmune liver disease panel (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cholangitis (formerly called primary biliary cirrhosis). This group of tests ...

  16. Update in Endocrine Autoimmunity


    Anderson, Mark S.


    Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

  17. Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis

    NARCIS (Netherlands)

    Koopman, F. A.; van Maanen, M. A.; Vervoordeldonk, M. J.; Tak, P. P.


    Imbalance in the autonomic nervous system (ANS) has been observed in many established chronic autoimmune diseases, including rheumatoid arthritis (RA), which is a prototypic immune-mediated inflammatory disease (IMID). We recently discovered that autonomic dysfunction precedes and predicts arthritis

  18. Autonomic Neuropathy (United States)

    ... risk of autonomic neuropathy. Other diseases. Amyloidosis, porphyria, hypothyroidism and cancer (usually due to side effects from treatment) may also increase the risk of autonomic neuropathy. ...

  19. Autoimmune Pancreatitis. (United States)

    Majumder, Shounak; Takahashi, Naoki; Chari, Suresh T


    Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) and typically presents with obstructive jaundice. Idiopathic duct-centric pancreatitis (IDCP) is a closely related but distinct disease that mimics AIP radiologically but manifests clinically most commonly as recurrent acute pancreatitis in young individuals with concurrent inflammatory bowel disease. IgG4 levels are often elevated in AIP and normal in IDCP. Histologically, lymphoplasmacytic acinar inflammation and storiform fibrosis are seen in both. In addition, the histologic hallmark of IDCP is the granulocyte epithelial lesion: intraluminal and intraepithelial neutrophils in medium-sized and small ducts with or without granulocytic acinar inflammation often associated with destruction of ductal architecture. Initial treatment of both AIP and IDCP is with oral corticosteroids for duration of 4 weeks followed by a gradual taper. Relapses are common in AIP and relatively uncommon in IDCP, a relatively rare disease for which the natural history is not well understood. For patients with relapsing AIP, treatment with immunomodulators and more recently rituximab has been recommended. Although rare instances of pancreaticobiliary malignancy has been reported in patients with AIP, overall the lifetime risk of developing pancreatic cancer does not appear to be elevated.

  20. Susceptibility Genes in Thyroid Autoimmunity

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    Yoshiyuki Ban


    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  1. Autoimmunity and Gastric Cancer (United States)

    Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo


    Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

  2. Inheritable and sporadic non-autoimmune hyperthyroidism. (United States)

    Ferraz, Carolina; Paschke, Ralf


    Hyperthyroidism is a clinical state that results from high thyroid hormone levels which has multiple etiologies, manifestations, and potential therapies. Excluding the autoimmune Graves disease, autonomic adenomas account for the most import cause of non-autoimmune hyperthyroidism. Activating germline mutations of the TSH receptor are rare etiologies for hyperthyroidism. They can be inherited in an autosomal dominant manner (familial or hereditary, FNAH), or may occur sporadically as a de novo condition, also called: persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH). These three conditions: autonomic adenoma, FNAH and PSNAH constitute the inheritable and sporadic non-autoimmune hyperthyroidism. Particularities in epidemiology, etiology, molecular and clinical aspects of these three entities will be discussed in this review in order to guide to an accurate diagnosis allowing among others genetic counseling and presymptomatic diagnosis for the affected families. The optimal treatment based on the right diagnosis will avoid consequences of a persistent or relapsing hyperthyroidism. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  3. Type 1 diabetes and polyglandular autoimmune syndrome: A review (United States)

    Hansen, Martin P; Matheis, Nina; Kahaly, George J


    Type 1 diabetes (T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1D as a monoglandular disease and the relation to polyglandular autoimmune syndrome (PAS) have also been well explored. The incidence of T1D has steadily increased in most parts of the world, especially in industrialized nations. T1D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterial-induced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type III, which encompasses T1D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome. PMID:25685279

  4. Galectin-3 in autoimmunity and autoimmune diseases. (United States)

    de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea


    Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell-cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte-macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. © 2015 by the Society for Experimental Biology and Medicine.

  5. Autonomous houses. Autonomous house

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, S. (Tokai University, Tokyo (Japan). Faculty of Engineering)


    Self-sufficiency type houses are outlined. On condition that people gain a certain amount of income in relation with the society, they self-suffice under the given environment, allowing themselves to accept a minimum of industrial products with small environmental load. Ordinary supply from outside of fossil energy and materials which depend on it is minimized. Types are classified into three: energy, energy materials and perfect self-sufficiency. A study project for environment symbiotic houses is progressing which is planned by the Ministry of Construction and Institute of Building Energy Conservation and is invested by a private company. Its target is making a house for halving an environmental load by CO{sub 2}, for the purpose of creating the environment symbiotic house which is nice to and in harmony with the global environment and human beings. As a part of the studies on energy-saving and resource conservation on houses, introduced is a plan of an autonomous house at Izu-Atagawa. The passive method and high thermal-insulation are used for air conditioning, and hot spring water for hot water supply. Electric power is generated by hydroelectric power generation using mountain streams and by solar cells. Staple food is purchased, while subsidiary food is sufficed. 17 refs., 4 figs., 1 tab.

  6. The Autoimmune Ecology. (United States)

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana


    Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  7. Bistability in autoimmune diseases

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Mosekilde, Erik; Lund, Ole


    Autoimmune diseases damage host tissue, which, in turn, may trigger a stronger immune response. Systems characterized by such positive feedback loops can display co-existing stable steady states. In a mathematical model of autoimmune disease, one steady state may correspond to the healthy state...

  8. Update in endocrine autoimmunity. (United States)

    Anderson, Mark S


    The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.


    Directory of Open Access Journals (Sweden)

    Juan-Manuel eAnaya


    Full Text Available Autoimmune diseases (ADs represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology, which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation. As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology. In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics to favor or protect against autoimmunity and its outcomes. Herein we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status, gender and sex hormones, vitamin D, organic solvents and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  10. [Non-autoimmune thyroiditis]. (United States)

    Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D


    The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

  11. Autonomous search

    CERN Document Server

    Hamadi, Youssef; Saubion, Frédéric


    Autonomous combinatorial search (AS) represents a new field in combinatorial problem solving. Its major standpoint and originality is that it considers that problem solvers must be capable of self-improvement operations. This is the first book dedicated to AS.

  12. Stress proteins, autoimmunity, and autoimmune disease. (United States)

    Winfield, J B; Jarjour, W N


    At birth, the immune system is biased toward recognition of microbial antigens in order to protect the host from infection. Recent data suggest that an important initial line of defense in this regard involves autologous stress proteins, especially conserved peptides of hsp60, which are presented to T cells bearing gamma delta receptors by relatively nonpolymorphic class lb molecules. Natural antibodies may represent a parallel B cell mechanism. Through an evolving process of "physiological" autoreactivity and selection by immunodominant stress proteins common to all prokaryotes, B and T cell repertoires expand during life to meet the continuing challenge of infection. Because stress proteins of bacteria are homologous with stress proteins of the host, there exists in genetically susceptible individuals a constant risk of autoimmune disease due to failure of mechanisms for self-nonself discrimination. That stress proteins actually play a role in autoimmune processes is supported by a growing body of evidence which, collectively, suggests that autoreactivity in chronic inflammatory arthritis involves, at least initially, gamma delta cells which recognize epitopes of the stress protein hsp60. Alternate mechanisms for T cell stimulation by stress proteins undoubtedly also exist, e.g., molecular mimicry of the DR beta third hypervariable region susceptibility locus for rheumatoid arthritis by a DnaJ stress protein epitope in gram-negative bacteria. While there still is confusion with respect to the most relevant stress protein epitopes, a central role for stress proteins in the etiology of arthritis appears likely. Furthermore, insight derived from the work thus far in adjuvant-induced arthritis already is stimulating analyses of related phenomena in autoimmune diseases other than those involving joints. Only limited data are available in the area of humoral autoimmunity to stress proteins. Autoantibodies to a number of stress proteins have been identified in SLE and

  13. Autoantibodies in Autoimmune Hepatitis. (United States)

    Muratori, Luigi; Deleonardi, Gaia; Lalanne, Claudine; Barbato, Erica; Tovoli, Alessandra; Libra, Alessia; Lenzi, Marco; Cassani, Fabio; Muratori, Paolo


    The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed. © 2015 S. Karger AG, Basel.

  14. Vaccines, adjuvants and autoimmunity. (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda


    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Eosinophils in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Daniela Čiháková


    Full Text Available Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

  16. Eosinophils in Autoimmune Diseases (United States)

    Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela


    Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

  17. Autoimmune diseases in asthma. (United States)

    Tirosh, Amir; Mandel, Dror; Mimouni, Francis B; Zimlichman, Eyal; Shochat, Tzippora; Kochba, Ilan


    Previous research has suggested an inverse relationship between T-helper 2-related atopic disorders, such as asthma, and T-helper 1-related autoimmune diseases. One controversial hypothesis postulates that asthma provides a protective effect for the development of autoimmune-related disorders. To assess the rate of newly diagnosed autoimmune disorders in a large cohort of young adults. Using cross-sectional data from the Israeli Defense Force database, the authors analyzed the prevalence of autoimmune disorders in asthmatic and nonasthmatic military personnel between 1980 and 2003. A follow-up study traced newly diagnosed autoimmune disorders among asthmatic and nonasthmatic individuals from the time of enrollment in military service until discharge (22 and 36 months for women and men, respectively). General community. 307,367 male and 181,474 female soldiers in compulsory military service who were between 18 and 21 years of age. Cases of type 1 diabetes mellitus, vasculitis, immune thrombocytopenic purpura, inflammatory bowel disease, rheumatoid arthritis, and the antiphospholipid syndrome. Of 488,841 participants at enrollment, significantly more women than men had autoimmune disorders. Compared with asthmatic women, nonasthmatic women had a significantly higher prevalence of all autoimmune disorders except for the antiphospholipid syndrome. Type 1 diabetes mellitus, vasculitis, and rheumatoid arthritis were less prevalent in men with asthma than in those without. During the follow-up period, vasculitis and rheumatoid arthritis were more frequently diagnosed in nonasthmatic persons of both sexes. There was a significantly higher incidence of immune thrombocytopenic purpura, inflammatory bowel disease, and the antiphospholipid syndrome in nonasthmatic women and a statistically significantly higher incidence of type 1 diabetes mellitus in nonasthmatic men. The study was limited to a population of young military recruits; therefore, its findings are not necessarily

  18. Autoimmune gastritis: Pathologist's viewpoint. (United States)

    Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo


    Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling.

  19. Curcumin and autoimmune disease. (United States)

    Bright, John J


    The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

  20. Headache in autoimmune diseases. (United States)

    John, Seby; Hajj-Ali, Rula A


    Autoimmune diseases are a group of heterogeneous inflammatory disorders characterized by systemic or localized inflammation, leading to ischemia and tissue destruction. These include disorders like systemic lupus erythematosus and related diseases, systemic vasculitides, and central nervous system (CNS) vasculitis (primary or secondary). Headache is a very common manifestation of CNS involvement of these diseases. Although headache characteristics can be unspecific and often non-diagnostic, it is important to recognize because headache can be the first manifestation of CNS involvement. Prompt recognition and treatment is necessary not only to treat the headache, but also to help prevent serious neurological sequelae that frequently accompany autoimmune diseases. In this review, we discuss headache associated with autoimmune diseases along with important mimics. © 2014 American Headache Society.

  1. [Autoimmune thyroid disease and other non-endocrine autoimmune diseases]. (United States)

    Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana


    Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

  2. The thyroid and autoimmunity

    International Nuclear Information System (INIS)

    Drexhage, H.A.; Wiersinga, W.M.


    These proceedings give an almost complete picture of what is presently known on the autoimmune aspects of both functional and growth disturbances of the thyroid gland. It comprises 12 reviews on main areas of present research, each followed by shorter communications of work in progress relevant to the topic. (Auth.)

  3. Paraneoplastic autoimmune movement disorders. (United States)

    Lim, Thien Thien


    To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders. The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome. Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. [Autoimmune hepatitis: Immunological diagnosis]. (United States)

    Brahim, Imane; Brahim, Ikram; Hazime, Raja; Admou, Brahim


    Autoimmune hepatopathies (AIHT) including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune cholangitis (AIC), represent an impressive entities in clinical practice. Their pathogenesis is not perfectly elucidated. Several factors are involved in the initiation of hepatic autoimmune and inflammatory phenomena such as genetic predisposition, molecular mimicry and/or abnormalities of T-regulatory lymphocytes. AIHT have a wide spectrum of presentation, ranging from asymptomatic forms to severe acute liver failure. The diagnosis of AIHT is based on the presence of hyperglobulinemia, cytolysis, cholestasis, typical even specific circulating auto-antibodies, distinctive of AIH or PBC, and histological abnormalities as well as necrosis and inflammation. Anti-F actin, anti-LKM1, anti-LC1 antibodies permit to distinguish between AIH type 1 and AIH type 2. Anti-SLA/LP antibodies are rather associated to more severe hepatitis, and particularly useful for the diagnosis of seronegative AIH for other the antibodies. Due to the relevant diagnostic value of anti-M2, anti-Sp100, and anti-gp210 antibodies, the diagnosis of PBC is more affordable than that of PSC and AIC. Based on clinical data, the immunological diagnosis of AIHT takes advantage of the various specialized laboratory techniques including immunofluorescence, immunodot or blot, and the Elisa systems, provided of a closer collaboration between the biologist and the physician. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Autoimmune paediatric liver disease. (United States)

    Mieli-Vergani, Giorgina; Vergani, Diego


    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

  6. Nonsegmental Vitiligo and Autoimmune Mechanism

    Directory of Open Access Journals (Sweden)

    Naoki Oiso


    Full Text Available Nonsegmental vitiligo is a depigmented skin disorder showing acquired, progressive, and depigmented lesions of the skin, mucosa, and hair. It is believed to be caused mainly by the autoimmune loss of melanocytes from the involved areas. It is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases including Hashimoto's thyroiditis and Graves' disease, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, systemic lupus erythematosus, Addison's disease, and alopecia areata. This indicates the presence of genetically determined susceptibility to not only vitiligo but also to other autoimmune disorders. Here, we summarize current understanding of autoimmune pathogenesis in non-segmental vitiligo.

  7. Diabetic peripheral neuropathy, is it an autoimmune disease? (United States)

    Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread


    Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (pneuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Peptides Against Autoimmune Neurodegeneration. (United States)

    Stepanov, Alexey; Lomakin, Yakov; Gabibov, Alexander; Belogurov, Alexey


    The mammalian immune system is a nearly perfect defensive system polished by a hundred million years of evolution. Unique flexibility and adaptivity have created a virtually impenetrable barrier to numerous exogenous pathogens that are assaulting us every moment. Unfortunately, triggers that remain mostly enigmatic will sometimes persuade the immune system to retarget against self-antigens. This civil war remains underway, showing no mercy and taking no captives, eventually leading to irreversible pathological changes in the human body. Research that has emerged during the last two decades has given us hope that we may have a chance to overcome autoimmune diseases using a variety of techniques to "reset" the immune system. In this report, we summarize recent advances in utilizing short polypeptides - mostly fragments of autoantigens - in the treatment of autoimmune neurodegeneration. Copyright© Bentham Science Publishers; For any queries, please email at

  9. Sarcoidosis and Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Piera Fazzi


    Full Text Available Most of the studies have shown a higher risk for subclinical and clinical hypothyroidism, antithyroid autoantibodies [overall antithyroid peroxidase antibodies (TPOAb], and in general, thyroid autoimmunity, overall in the female gender in patients with sarcoidosis (S. A significantly higher prevalence of clinical hypothyroidism and Graves’ disease was also described in female S patients with respect to controls. Gallium-67 (Ga-67 scyntigraphy in S patients, in the case of thyroid uptake, suggests the presence of aggressive autoimmune thyroiditis and hypothyroidism. For this reason, ultrasonography and thyroid function should be done in the case of Ga-67 thyroid uptake. In conclusion, thyroid function, TPOAb measurement, and ultrasonography should be done to assess the clinical profile in female S patients, and the ones at high risk (female individuals, with TPOAb positivity, and hypoechoic and small thyroid should have periodically thyroid function evaluations and suitable treatments.

  10. Autoimmune Addison's disease. (United States)

    Napier, Catherine; Pearce, Simon H S


    Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease. Copyright © 2012. Published by Elsevier Masson SAS.

  11. Autoimmune thyrotoxicosis: diagnostic challenges. (United States)

    Ponto, Katharina A; Kahaly, George J


    Autoimmune thyrotoxicosis or Graves' disease (GD) is the most common cause of hyperthyroidism in the United States (full text available online: GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders. Copyright © 2012. Published by Elsevier Inc.

  12. Autoimmune liver disease 2007. (United States)

    Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B


    Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

  13. Autoimmune liver disease and therapy in childhood

    Directory of Open Access Journals (Sweden)

    Matjaž Homan


    Full Text Available Autoimmune hepatitis is a chronic immune-mediated disease of the liver. In childhood, autoimmune liver disorders include autoimmune hepatitis type I and II, autoimmune sclerosing cholangitis, Coombs-positive giant cell hepatitis, and de novo autoimmune hepatitis after liver transplantation. Autoimmune liver disease has a more aggressive course in children, especially autoimmune hepatitis type II. Standard therapy is a combination of corticosteroids and azathioprine. Around 80 % of children with autoimmune liver disease show a rapid response to combination therapy. The non-responders are treated with more potent drugs, otherwise autoimmune disease progresses to cirrhosis of the liver and the child needs liver transplantation as rescue therapy.

  14. [Treatment of autoimmune hepatic diseases]. (United States)

    Bueverov, A O


    The immunosuppresive drugs, primarily glucocorticosteroids, serve as the basis for the pathogenetic treatment of autoimmune diseases of the liver. In autoimmune hepatitis, immunosuppressive therapy induces and maintains persistent remission in most patients while in primary biliary cirrhosis and primary sclerosing cholangitis, its capacities are substantially limited. Ursodeoxycholic acid is used as the basic drug in predominantly occurring intrahepatic cholestasis. The treatment of cross autoimmune syndromes generally requires the choice of a combination of drugs.

  15. Autoimmune hepatitis vs. pregnancy

    Directory of Open Access Journals (Sweden)

    Olga Adamczyk-Gruszka


    Full Text Available Introduction Autoimmune hepatitis (AIH is a disease of unknown etiology. In pregnancy, it may have mild clinical course as well as can lead to liver failure, or exacerbation of clinical symptoms. In pregnant women the severity of symptoms is often observed between the second and third trimester, and in the puerperium. The disease is marked by enhanced activity of Th lymphocytes, which hepatocytes recognize as foreign antigens. This results in interleukin production activating B lymphocytes, and the production of specific antibodies attacking and destroying the hepatocytes. Case report A 35-year old patient, CII PII, 7 Hbd, with autoimmune hepatitis reported for a check-up. Her first pregnancy was 18 years ago, without history of underlying disease, carried to term without complications. The woman gave birth to a baby-son weighing 3,280g, 10 points Apgar. The delivery was spontaneous and uneventful. The patient got pregnant after an 18-year break. When she twice-tested positively for pregnancy, the treatment with azathioprine was switched to prednisolone. Over the pregnancy the patient was hospitalized 4 times, in 25, 29, 35, and 37 week of gestation due to a threat of preterm delivery, and pregnancy-related cholestasis associated with AIH. In 37 week of gestation, delivery was induced, and she gave birth to a healthy male, weighing 2,650 g, body height of 49 cm, 10 points Apgar scale. The liver function improved and stabilized after the delivery. Treatment with prednisolone has been continued, and the patient’s condition is still controlled. Pregnant patients with autoimmune hepatitis often experience exacerbation of the disease, especially in the third trimester, and in the postpartum period. This case shows that with proper care it is possible to continue and terminate pregnancy safely for the mother and her newly born baby.

  16. Maternal history of autoimmune disease in children presenting with tics and/or obsessive-compulsive disorder. (United States)

    Murphy, T K; Storch, E A; Turner, A; Reid, J M; Tan, J; Lewin, A B


    A commonality across a number of pediatric neuropsychiatric disorders is a higher than typical rate of familial - and especially maternal - autoimmune disease. Of recent interest, a subtype of obsessive-compulsive disorder (OCD) and tic disorders known collectively as Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is believed to be secondary to central nervous system (CNS) autoimmunity that occurs in relation to group A streptococcal infection. Thus, we hypothesized that a sample of children with OCD and/or tics would have an increased maternal risk for an autoimmune response relative to population norms. We also expected maternal prevalence of various autoimmune diseases to be higher among those participants that met the putative criteria for PANDAS. We examined, via structured interview, the medical history of the biological mothers of 107 children with OCD and/or tics. Autoimmune disorders were reported in 17.8% of study mothers, which is significantly greater than the general prevalence among women in the United States (approximately 5%). Further, study mothers were more likely to report having an autoimmune disease if their children were considered "likely PANDAS" cases versus "unlikely PANDAS" cases. The results offer preliminary support for hypothesized links between maternal autoimmune disease and both OCD/tics and PANDAS in youth. Further research is necessary to clarify these general associations; links to specific autoimmune disease; and relevance of autoimmune disease in other family members (e.g., fathers). Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Steroids and Autoimmunity. (United States)

    Trombetta, Amelia Chiara; Meroni, Marianna; Cutolo, Maurizio


    From the middle of the 19th century, it is known that endocrine and immune systems interact bi-directionally in different processes that ensure organism homeostasis. Endocrine and nervous systems have a pivotal role in the balancing of pro- and anti-inflammatory functions of immune system, and constitute a complex circadian neuroendocrine network. Autoimmune diseases have in fact a complex pathogenic origin in which the importance of endocrine system was demonstrated. In this chapter, we will mention the structure and function of steroidal hormones involved in the neuroendocrine immune network and we will address the ways in which endocrine and immune systems influence each other, in a bi-directional fashion. Adrenal hormones, sex hormones, vitamin D, and melatonin and prolactin importantly all contribute to the homeostasis of the immune system. Indeed, some of the steroidal hormone activities determine inhibition or stimulation of immune system components, in both physiological (i.e. suppression of an unwanted response in pregnancy, or stimulation of a protective response in infections) and pathological conditions. We will finally mention the rationale for optimization of exogenous administration of glucocorticoids in chronic autoimmune diseases, and the latest developments concerning these drugs. © 2017 S. Karger AG, Basel.

  18. Current topics in autoimmune hepatitis. (United States)

    Muratori, Luigi; Muratori, Paolo; Granito, Alessandro; Pappas, Giorgios; Cassani, Fabio; Lenzi, Marco


    Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by "impaired" regulatory T cells and the development of novel animal models of autoimmune hepatitis. Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  19. Increased polyamines alter chromatin and stabilize autoantigens in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Wesley H. Brooks


    Full Text Available Polyamines are small cations with unique combinations of charge and length that give them many putative interactions in cells. Polyamines are essential since they are involved in replication, transcription, translation, and stabilization of macro-molecular complexes. However, polyamine synthesis competes with cellular methylation for S-adenosylmethionine, the methyl donor. Also, polyamine degradation can generate reactive molecules like acrolein. Therefore, polyamine levels are tightly controlled. This control may be compromised in autoimmune diseases since elevated polyamine levels are seen in autoimmune diseases. Here a hypothesis is presented explaining how polyamines can stabilize autoantigens. In addition, the hypothesis explains how polyamines can inappropriately activate enzymes involved in NETosis, a process in which chromatin is modified and extruded from cells as extracellular traps that bind pathogens during an immune response. This polyamine-induced enzymatic activity can lead to an increase in NETosis resulting in release of autoantigenic material and tissue damage.

  20. Autoimmune premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Beata Komorowska


    Full Text Available Premature ovarian failure (POF, also termed as primary ovarian insufficiency (POI, is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.

  1. Autoimmune hepatitis in children. (United States)

    Mieli-Vergani, Giorgina; Vergani, Diego


    AIH, ASC, and de novo AIH after liver transplantation are childhood liver diseases of an autoimmune nature. The mode of presentation of AIH in childhood is variable, and the disease should be suspected and excluded in all children presenting with symptoms and signs of prolonged or severe acute liver disease. Although corticosteroids are effective in all types of childhood AIH, patients with LKM1 have a higher frequency of acute hepatic failure and relapse after corticosteroid withdrawal than do patients with ANA/SMA. ASC occurs commonly in the absence of inflammatory bowel disease, requires cholangiography for diagnosis, and improves during corticosteroid therapy. The development of AIH de novo in children who undergo liver transplantation for nonautoimmune liver disease may reflect interference with the maturation of T cells by immunosuppressive drugs.

  2. Recent advances in understanding autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Bliddal, Sofie; Nielsen, Claus Henrik; Feldt-Rasmussen, Ulla


    Autoimmune thyroid disease (AITD) is often observed together with other autoimmune diseases. The coexistence of two or more autoimmune diseases in the same patient is referred to as polyautoimmunity, and AITD is the autoimmune disease most frequently involved. The occurrence of polyautoimmunity h...

  3. [Stress and auto-immunity]. (United States)

    Delévaux, I; Chamoux, A; Aumaître, O


    The etiology of auto-immune disorders is multifactorial. Stress is probably a participating factor. Indeed, a high proportion of patients with auto-immune diseases report uncommon stress before disease onset or disease flare. The biological consequences of stress are increasingly well understood. Glucocorticoids and catecholamines released by hypothalamic-pituitary-adrenal axis during stress will alter the balance Th1/Th2 and the balance Th17/Treg. Stress impairs cellular immunity, decreases immune tolerance and stimulates humoral immunity exposing individuals to autoimmune disease among others. The treatment for autoimmune disease should include stress management. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. Celiac disease and endocrine autoimmunity. (United States)

    Kahaly, George J; Schuppan, Detlef


    Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives. © 2015 S. Karger AG, Basel.

  5. Autonomic Nervous System Disorders (United States)

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  6. Autoimmune Thyroiditis and Glomerulopathies

    Directory of Open Access Journals (Sweden)

    Domenico Santoro


    Full Text Available Autoimmune thyroiditis (AIT is generally associated with hypothyroidism. It affects ~2% of the female population and 0.2% of the male population. The evidence of thyroid function- and thyroid autoantibody-unrelated microproteinuria in almost half of patients with AIT and sometimes heavy proteinuria as in the nephrotic syndrome point to a link of AIT with renal disease. The most common renal diseases observed in AIT are membranous nephropathy, membranoproliferative glomerulonephritis, minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis, antineutrophil cytoplasmic autoantibody (ANCA vasculitis, and amyloidosis. Different hypotheses have been put forward regarding the relationship between AIT and glomerulopathies, and several potential mechanisms for this association have been considered. Glomerular deposition of immunocomplexes of thyroglobulin and autoantibodies as well as the impaired immune tolerance for megalin (a thyrotropin-regulated glycoprotein expressed on thyroid cells are the most probable mechanisms. Cross-reactivity between antigens in the setting of genetic predisposition has been considered as a potential mechanism that links the described association between ANCA vasculitis and AIT.


    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez


    Full Text Available Autoimmune bullous skin diseases (ABDs are uncommon, potentially fatal diseases of skin and mucous membranes which are associated with deposits of autoantibodies and complement against distinct molecules of the epidermis and dermal/epidermal basement membrane zone (BMZ. These autoantibodies lead to a loss in skin molecular integrity, which manifests clinically as formation of blisters or erosions. In pemphigus vulgaris, loss of adhesion occurs within the epidermis. The pioneering work of Ernst H. Beutner, Ph.D. and Robert E. Jordon, M.D. confirmed the autoimmune nature of these diseases. Walter F. Lever, M.D. contributed significantly to our understanding of the histopathologic features of these diseases. Walter Lever, M.D. and Ken Hashimoto, M.D. contributed electron microscopic studies of these diseases, especially in pemphigus vulgaris and bullous pemphigoid. In bullous pemphigoid (BP, linear IgA bullous dermatosis, epidermolysis bullosa acquisita (EBA and dermatitis herpetiformis (DH, loss of adhesion takes place within or underneath the BMZ. Classic EBA demonstrates extensive skin fragility; DH is commonly associated with gluten-sensitive enteropathy, and manifests clinically with pruritic papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The clinical spectrum of bullous pemphigoid includes tense blisters, urticarial plaques, and prurigo-like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy, and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a „cluster of jewels”-like pattern in childhood (chronic bullous disease of childhood and is more clinically heterogeneous in adulthood. Many of the autoantigens in these disorders are known and have been well characterized. ABDs may be influenced by both genetic and exogenous factors. The diagnoses of

  8. Autoimmune liver disease in children. (United States)

    Mieli-Vergani, G; Vergani, D


    Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.

  9. Intraocular inflammation in autoimmune diseases. (United States)

    Pras, Eran; Neumann, Ron; Zandman-Goddard, Gisele; Levy, Yair; Assia, Ehud I; Shoenfeld, Yehuda; Langevitz, Pnina


    The uveal tract represents the vascular organ of the eye. In addition to providing most of the blood supply to the intraocular structures, it acts as a conduit for immune cells, particularly lymphocytes, to enter the eye. Consequently, the uveal tract is represented in many intraocular inflammatory processes. Uveitis is probably a misnomer unless antigens within the uvea are the direct targets of the inflammatory process. A better term of the condition is "intraocular inflammation" (IOI). To review the presence of IOI in autoimmune diseases, the immunopathogenic mechanisms leading to disease, and treatment. We reviewed the English medical literature by using MEDLINE (1984-2003) employing the terms "uveitis," "intraocular inflammation," and "autoimmune diseases." An underlying autoimmune disease was identified in up to 40% of patients with IOI, and included spondyloarthropathies, Behcets disease, sarcoidosis, juvenile chronic arthritis, Vogt-Koyanagi-Harada syndrome (an inflammatory syndrome including uveitis with dermatologic and neurologic manifestations), immune recovery syndrome, and uveitis with tubulointerstitial disease. The immunopathogenesis of IOI involves enhanced T-cell response. Recently, guidelines for the use of immunosuppressive drugs for inflammatory eye disease were established and include: corticosteroids, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, cyclophosphamide, and chlorambucil. New therapies with limited experience include the tumor necrosis factor alpha inhibitors, interferon alfa, monoclonal antibodies against lymphocyte surface antigens, intravenous immunoglobulin (IVIG), and the intraocular delivery of immunosuppressive agents. An underlying autoimmune disease was identified in up to 40% of patients with IOI. Immunosuppressive drugs, biologic agents, and IVIG are employed for the treatment of IOI in autoimmune diseases.

  10. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M


    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  11. Type 1 autoimmune pancreatitis. (United States)

    Zen, Yoh; Bogdanos, Dimitrios P; Kawa, Shigeyuki


    Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed

  12. Type 1 autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Zen Yoh


    Full Text Available Abstract Before the concept of autoimmune pancreatitis (AIP was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of

  13. Autoimmune pancreatitis. An update

    International Nuclear Information System (INIS)

    Helmberger, T.


    Autoimmune pancreatitis (AIP) is a rare disease, the pathophysiological understanding of which has been greatly improved over the last years. The most common form, type 1 AIP belongs to the IgG4-related diseases and must be distinguished from type 2 AIP, which is a much rarer entity associated with chronic inflammatory bowel disease. Clinically, there is an overlap with pancreatic cancer. Imaging and further criteria, such as serological and histological parameters are utilized for a differentiation between both entities in order to select the appropriate therapy and to avoid the small but ultimately unnecessary number of pancreatectomies. The diagnostics of AIP are complex, whereby the consensus criteria of the International Association of Pancreatology have become accepted as the parameters for discrimination. These encompass five cardinal criteria and one therapeutic criterion. By applying these criteria AIP can be diagnosed with a sensitivity of 84.9 %, a specificity of 100 % and an accuracy of 93.8 %. The diagnosis of AIP is accomplished by applying several parameters of which two relate to imaging. As for the routine diagnostics of the pancreas these are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Important for the differential diagnosis is the exclusion of signs of local and remote tumor spread for which CT and MRI are established. The essential diagnostic parameter of histology necessitates sufficient sample material, which cannot usually be acquired by a fine needle biopsy. CT or MRI are the reference standard methods for identification of the optimal puncture site and imaging-assisted (TruCut) biopsy. In patients presenting with unspecific upper abdominal pain, painless jaundice combined with the suspicion of a pancreatic malignancy in imaging but a mismatch of secondary signs of malignancy, AIP should also be considered as a differential diagnosis. As the diagnosis of AIP only partially relies on imaging radiologists also

  14. Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen. (United States)

    Alimohammadi, Mohammad; Dubois, Noémie; Sköldberg, Filip; Hallgren, Asa; Tardivel, Isabelle; Hedstrand, Håkan; Haavik, Jan; Husebye, Eystein S; Gustafsson, Jan; Rorsman, Fredrik; Meloni, Antonella; Janson, Christer; Vialettes, Bernard; Kajosaari, Merja; Egner, William; Sargur, Ravishankar; Pontén, Fredrik; Amoura, Zahir; Grimfeld, Alain; De Luca, Filippo; Betterle, Corrado; Perheentupa, Jaakko; Kämpe, Olle; Carel, Jean-Claude


    Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

  15. Free radical theory of autoimmunity

    Directory of Open Access Journals (Sweden)

    Kannan Subburaj


    Full Text Available Abstract Background Despite great advances in clinical oncology, the molecular mechanisms underlying the failure of chemotherapeutic intervention in treating lymphoproliferative and related disorders are not well understood. Hypothesis A hypothetical scheme to explain the damage induced by chemotherapy and associated chronic oxidative stress is proposed on the basis of published literature, experimental data and anecdotal observations. Brief accounts of multidrug resistance, lymphoid malignancy, the cellular and molecular basis of autoimmunity and chronic oxidative stress are assembled to form a basis for the hypothesis and to indicate the likelihood that it is valid in vivo. Conclusion The argument set forward in this article suggests a possible mechanism for the development of autoimmunity. According to this view, the various sorts of damage induced by chemotherapy have a role in the pattern of drug resistance, which is associated with the initiation of autoimmunity.

  16. RNAi Therapeutics in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Seunghee Cha


    Full Text Available Since the discovery of RNA interference (RNAi, excitement has grown over its potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to change biological processes post-transcriptionally in various health conditions such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA enhances stability and specificity of RNAi-based approaches whereas it has to reduce or prevent undesirable immune responses or off-target effects. Recent advances in understanding pathogenesis of autoimmune diseases have allowed application of these tools in vitro as well as in vivo with some degree of success. Further research on the design and delivery of effectors of RNAi pathway and underlying molecular basis of RNAi would warrant practical use of RNAi-based therapeutics in human applications. This review will focus on the approaches used for current therapeutics and their applications in autoimmune diseases, including rheumatoid arthritis and Sjögren’s syndrome.

  17. Thyroid dysfunction: an autoimmune aspect. (United States)

    Khan, Farah Aziz; Al-Jameil, Noura; Khan, Mohammad Fareed; Al-Rashid, May; Tabassum, Hajera


    Auto immune thyroid disease (AITD) is the common organ specific autoimmune disorder, Hashimoto thyroiditis (HT) and Grave's disease (GD) are its well-known sequelae. It occurs due to loss of tolerance to autoantigens thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSH-R) which leads to the infiltration of the gland. T cells in chronic autoimmune thyroiditis (cAIT) induce apoptosis in thyroid follicular cells and cause destruction of the gland. Presences of TPO antibodies are common in HT and GD, while Tg has been reported as an independent predictor of thyroid malignancy. Cytokines are small proteins play an important role in autoimmunity, by stimulating B and T cells. Various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-α and IFN-γ are found in thyroid follicular cells which enhance inflammatory response with nitric oxide (NO) and prostaglandins.

  18. A minimum number of autoimmune T cells to induce autoimmunity?

    Czech Academy of Sciences Publication Activity Database

    Bosch, A.J.T.; Bolinger, B.; Keck, S.; Štěpánek, Ondřej; Ozga, A.J.; Galati-Fournier, V.; Stein, J.V.; Palmer, E.


    Roč. 316, jaro (2017), s. 21-31 ISSN 0008-8749 R&D Projects: GA ČR GJ16-09208Y Institutional support: RVO:68378050 Keywords : T cell * Tolerance * Autoimmunity Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Immunology Impact factor: 3.172, year: 2016

  19. Multiplex autoantibody detection for autoimmune liver diseases and autoimmune gastritis. (United States)

    Vanderlocht, Joris; van der Cruys, Mart; Stals, Frans; Bakker-Jonges, Liesbeth; Damoiseaux, Jan


    Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs. For the autoimmune liver diseases and AIG, respectively, 64 and 36 samples were tested. For anti-mitochondrial and anti-smooth muscle antibodies a concordance rate of 97% and 88% was observed, respectively. The concordance rate for anti-parietal cell antibodies was 92% when samples without EQC consensus (n=15) were excluded. For antibodies against intrinsic factor a concordance of 96% was observed. For all these antibodies discrepancies were identified that relate to the different test characteristics and the preponderance of IIF utilizing labs in the EQC program. In conclusion, we observed good agreement of the tested DIA blots with the consensus results of the Dutch EQC program. Taken together with the logistic advantages these blots are a good alternative for autoantibody detection in the respective diseases. A large prospective multicenter study is warranted to position these novel tests further in the whole spectrum of assays for the detection of these antibodies in a routine autoimmune laboratory. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Testing for autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J


    Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course of the di......Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course...

  1. Leaky gut and autoimmune diseases. (United States)

    Fasano, Alessio


    Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases.

  2. Vitiligo and Autoimmune Thyroid Disorders

    Directory of Open Access Journals (Sweden)

    Enke Baldini


    Full Text Available Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5–1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves’ disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s.

  3. [Type 2 autoimmune polyendocrine syndromes (APS-2)]. (United States)

    Vialettes, Bernard; Dubois-Leonardon, Noémie


    Type 2 autoimmune polyendocrine syndromes (APS-2) are the most frequent disorders associating several organ-specific autoimmune diseases. Their high prevalence is due to the fact that the main manifestations of APS-2, such as thyroidal autoimmunity, type 1 diabetes, autoimmune gastric atrophy and vitiligo, are common diseases. APS-2 represents a clinical model that can serve to help unravel the mechanisms underlying autoimmunity. Diagnosis of APS-2 is a challenge for the clinician, especially in poorly symptomatic forms, and may require systematic screening based on measurement of autoantibodies and functional markers.

  4. Semi-Autonomous Systems Laboratory (United States)

    Federal Laboratory Consortium — VisionThe Semi-Autonomous Systems Lab focuses on developing a comprehensive framework for semi-autonomous coordination of networked robotic systems. Semi-autonomous...

  5. Postural tachycardia syndrome (POTS) and other autonomic disorders in antiphospholipid (Hughes) syndrome (APS). (United States)

    Schofield, J R; Blitshteyn, S; Shoenfeld, Y; Hughes, G R V


    Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder that has been shown to cause a large number of cardiac and neurological manifestations. Two recent studies have demonstrated abnormalities in cardiovascular autonomic function testing in APS patients without other cardiovascular or autoimmune disease. However, an association between autonomic disorders such as postural tachycardia syndrome and APS has not previously been described. Data were obtained by retrospective chart review. We identified 15 patients who have been diagnosed with APS and an autonomic disorder. The median age of the patients at the time of data analysis was 39 years. The autonomic disorders seen in these patients included postural tachycardia syndrome, neurocardiogenic syncope and orthostatic hypotension. The majority of patients (14/15) were female and the majority (14/15) had non-thrombotic neurological manifestations of APS, most commonly migraine, memory loss and balance disorder. Many also had livedo reticularis (11/15) and Raynaud's phenomenon (nine of 15). In some patients, the autonomic manifestations improved with anticoagulation and/or anti-platelet therapy; in others they did not. Two patients with postural tachycardia syndrome who failed to improve with the usual treatment of APS have been treated with intravenous immunoglobulin with significant improvement in their autonomic symptoms. We believe that autonomic disorders in APS may represent an important clinical association with significant implications for treatment. © The Author(s) 2014 Reprints and permissions:

  6. The role of the autoimmunity laboratory in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    SS Hasson


    Full Text Available Laboratory testing is of great value when evaluating a patient with a suspected autoimmune disease. The results can confirm a diagnosis, estimate disease severity, aid in assessing prognosis and are useful to follow disease activity. Components of the laboratory exam include complete blood count with differential, comprehensive metabolic panel, inflammatory markers, autoantibodies, and flow cytometry. Currently, autoimmunity laboratories are very vibrant owing to the constant and increasing availability of new tests, mainly due to the detection of new autoantibodies. The main characteristic that differentiates the autoimmunity laboratory from other laboratories is the use of immunoassays such as enzyme-linked immunosorbent assay (ELISA, as basic techniques which determines antibodies (autoantibodies and not antigens. For this reason, immunoassay techniques must employ antigens as reagents. However, over the last few years, a significant trend at autoimmunity laboratories has been the gradual replacement of immunofluorescence microscopy by immunoassay. Nowadays the revolution of new technology has taken place significantly, for examples; recombinant DNA technology has allowed the production of large quantities of antigens for autoantibody analysis. Flow cytometry for the analysis of microsphere-based immunoassays allows the simultaneous measurement of several autoantibodies. In the same way, autoantigen microarrays provide a practical means to analyse biological fluids in the search for a high number of autoantibodies. We are now at the beginning of an era of multiplexed analysis, with a high capacity of autoantibody specificities. The future tendency in this field will include immunoassays with greater analytical sensitivity, specificity, simultaneous multiplexed capability, the use of protein microarrays, and the use of other technologies such as microfluidics.

  7. Genetic autonomic disorders. (United States)

    Axelrod, Felicia B


    Genetic disorders affecting the autonomic nervous system can result in abnormal development of the nervous system or they can be caused by neurotransmitter imbalance, an ion-channel disturbance or by storage of deleterious material. The symptoms indicating autonomic dysfunction, however, will depend upon whether the genetic lesion has disrupted peripheral or central autonomic centers or both. Because the autonomic nervous system is pervasive and affects every organ system in the body, autonomic dysfunction will result in impaired homeostasis and symptoms will vary. The possibility of genetic confirmation by molecular testing for specific diagnosis is increasing but treatments tend to remain only supportive and directed toward particular symptoms. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Management strategies for autoimmune pancreatitis. (United States)

    Kamisawa, Terumi; Takuma, Kensuke; Hara, Seiichi; Tabata, Taku; Kuruma, Sawako; Inaba, Yoshihiko; Gopalakrishna, Rajesh; Egawa, Naoto; Itokawa, Fumihide; Itoi, Takao


    Autoimmune pancreatitis (AIP) is a newly developed concept for a peculiar type of pancreatitis, and at present is recognized as a pancreatic lesion reflecting IgG4-related systemic disease. It is of utmost importance to differentiate AIP from pancreatic cancer to avoid unnecessary surgery. The current management strategies for AIP, including its clinical features, diagnostic criteria, clinical subtypes, steroid therapy and prognosis are discussed, based on our 66 AIP cases and papers searched in PubMed from 1992 to March 2011, using the term 'autoimmune pancreatitis'. A new clinicopathological entity, an 'IgG4-related sclerosing disease' is also mentioned. AIP should be considered in the differential diagnosis in elderly male patients presented with obstructive jaundice and pancreatic mass. Steroids are a standard therapy for AIP, but their regimen including maintenance therapy should be evaluated in prospective trials.

  9. Autoimmune encephalitis and sleep disorders

    Directory of Open Access Journals (Sweden)

    Yan HUANG


    Full Text Available Research shows that autoimmune encephalitis is associated with sleep disorders. Paraneoplastic neurological syndrome (PNS with Ma2 antibodies can cause sleep disorders, particularly narcolepsy and rapid eye movement sleep behavior disorder (RBD. Limbic encephalitis (LE and Morvan syndrome, associated with voltage - gated potassium channel (VGKC-complex antibodies, which include leucine-rich glioma-inactivated 1 (LGI1 antibody and contactin-associated protein 2 (Caspr2, can result in profound insomnia and other sleep disorders. Central neurogenic hypoventilation are found in patients with anti-N-methyl-D-aspartate (NMDA receptor encephalitis, whereas obstructive sleep apnea (OSA, stridor and parasomnia are prominent features of encephalopathy associated with IgLON5 antibodies. Sleep disorders are cardinal manifestations in patients with autoimmune encephalitis. Immunotherapy possiblely can improve clinical symptoms and prognosis in a positive way. DOI: 10.3969/j.issn.1672-6731.2017.10.004

  10. Progranulin antibodies in autoimmune diseases. (United States)

    Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael


    Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Autoimmune Thyroiditis and Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Angela Lopomo


    Full Text Available Autoimmune diseases (AIDs are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG. In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed.

  12. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ayesha Salahuddin


    Full Text Available Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.




    Purpose To report the presence of a hyperautofluorescent ring and corresponding spectral-domain optical coherence tomography (SD-OCT) features seen in patients with autoimmune retinopathy. Methods All eyes were evaluated by funduscopic examination, full-fleld electroretinography, fundus autofluorescence, and SD-OCT. Further confirmation of the diagnosis was obtained with immunoblot and immunohistochemistry testing of the patient’s serum. Humphrey visual fields and microperimetry were also performed. Results Funduscopic examination showed atrophic retinal pigment epithelium (RPE) associated with retinal artery narrowing but without pigment deposits. The scotopic and photopic full-field electroretinograms were nondetectable in three patients and showed a cone–rod pattern of dysfunction in one patient. Fundus autofluorescence revealed a hyperautofluorescent ring in the parafoveal region, and the corresponding SD-OCT demonstrated loss of the photoreceptor inner segment–outer segment junction with thinning of the outer nuclear layer from the region of the hyperautofluorescent ring toward the retinal periphery. The retinal layers were generally intact within the hyperautofluorescent ring, although the inner segment–outer segment junction was disrupted, and the outer nuclear layer and photoreceptor outer segment layer were thinned. Conclusion This case series revealed the structure of the hyperautofluorescent ring in autoimmune retinopathy using SD-OCT. Fundus autofluorescence and SD-OCT may aid in the diagnosis of autoimmune retinopathy and may serve as a tool to monitor its progression. PMID:22218149

  14. Autoimmune Thyroiditis and Myasthenia Gravis (United States)

    Lopomo, Angela; Berrih-Aknin, Sonia


    Autoimmune diseases (AIDs) are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD) is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG). In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed. PMID:28751878

  15. Vitamin D and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    E. A. Potrokhova


    Full Text Available The review discusses the effect of vitamin D on the tolerogenic modulation of an immune response, its relationship to cells of the monocyte-macrophage series, including dendritic cells, monocytes, and macrophages, in the context of the impact of the expression of anti-inflammatory proinflammatory cytokines in some autoimmune diseases (rheumatoid arthritis, systemic scleroderma, multiple sclerosis, type 1 diabetes mellitus, systemic lupus erythematosus, and Crohn`s disease. It discusses the role of vitamin D in the development of innate and adaptive immunity. Despite some conflicting evidence, the immune regulatory function of vitamin D is generally directed toward inhibition of the components of innate and acquired immunity, which are responsible for the induction of autoimmune reactions; in this connection there are a growing number of publications devoted to the issues of vitamin D supplementation in patients with autoimmune diseases, the preventive effect of vitamin D intake on the risk of an abnormality and that of therapeutic doses of the vitamin on its course. The maintenance of the threshold value for serum 25(OHD3 at least 30 ng/ml, which is achieved by the intake of about 2000 IU of vitamin D, is shown to be required for its immune regulatory function. The data given raise the question as to whether it is necessity to revise the Russian recommended daily dietary allowances for vitamin D through its infant food fortification.

  16. Diagnosing autoimmune pancreatitis with the Unifying-Autoimmune-Pancreatitis-Criteria. (United States)

    Schneider, Alexander; Michaely, Henrik; Rückert, Felix; Weiss, Christel; Ströbel, Philipp; Belle, Sebastian; Hirth, Michael; Wilhelm, Torsten J; Haas, Stephan L; Jesenofsky, Ralf; Schönberg, Stefan; Marx, Alexander; Singer, Manfred V; Ebert, Matthias P; Pfützer, Roland H; Löhr, J Matthias

    We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. From 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospectively validated our diagnostic approach in consecutive patients with a pancreatic lesion requiring surgery (Surgical-Cohort, n = 98). Overall, we identified 21 patients with AiP. Unifying-Autoimmune-Pancreatitis-Criteria and ICDC presented the highest diagnostic accuracies (each 98.8%), highest Youden indices (each 0.95238), and highest proportions of diagnosed patients (each n = 20/21, U-AIP/ICDC vs. other diagnostic systems, p Pancreatitis-Criteria revealed a satisfactory clinical applicability and offered an additional approach to diagnose AiP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  17. Autonomous Propellant Loading Project (United States)

    National Aeronautics and Space Administration — The AES Autonomous Propellant Loading (APL) project consists of three activities. The first is to develop software that will automatically control loading of...

  18. Autonomous Systems and Operations (United States)

    National Aeronautics and Space Administration — The AES Autonomous Systems and Operations (ASO) project will develop an understanding of the impacts of increasing communication time delays on mission operations,...

  19. Autonomous Star Tracker Algorithms

    DEFF Research Database (Denmark)

    Betto, Maurizio; Jørgensen, John Leif; Kilsgaard, Søren


    Proposal, in response to an ESA R.f.P., to design algorithms for autonomous star tracker operations.The proposal also included the development of a star tracker breadboard to test the algorithms performances.......Proposal, in response to an ESA R.f.P., to design algorithms for autonomous star tracker operations.The proposal also included the development of a star tracker breadboard to test the algorithms performances....

  20. A new combination of multiple autoimmune syndrome? Coexistence of vitiligo, autoimmune thyroid disease and ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Firdevs Topal


    Full Text Available The occurrence of three or more autoimmune disorders in one patient defines multiple autoimmune syndrome. The pathogenesis of multiple autoimmune syndrome is not known yet and environmental triggers and genetic susceptibility have been suggested to be involved. Herein, we report a 47-year-old woman who had Hashimoto’s thyroiditis, vitiligo and newly diagnosed ulcerative colitis. Diagnosis of ulcerative colitis was confirmed with histopathologic examination. This case presents a new combination of multiple autoimmune syndrome.

  1. Epidemiology of autoimmune diseases in Denmark

    DEFF Research Database (Denmark)

    Eaton, William W.; Rose, N.R.; Kalaydijan, A.


    An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate the population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise co-morbidities in i......An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate the population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise co...

  2. Autoimmune atrophic gastritis: current perspectives

    Directory of Open Access Journals (Sweden)

    Minalyan A


    Full Text Available Artem Minalyan,1 Jihane N Benhammou,1 Aida Artashesyan,1 Michael S Lewis,2 Joseph R Pisegna1 1Division of Gastroenterology, Hepatology and Parenteral Nutrition, 2Department of Pathology and Laboratory Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA Abstract: At present there is no universally accepted classification for gastritis. The first successful classification (The Sydney System that is still commonly used by medical professionals was first introduced by Misiewicz et al in Sydney in 1990. In fact, it was the first detailed classification after the discovery of Helicobacter pylori by Warren and Marshall in 1982. In 1994, the Updated Sydney System was proposed during the International Workshop on the Histopathology of Gastritis followed by the publication in The American Journal of Surgical Pathology by Dixon et al. Using the new classification, distinction between atrophic and nonatrophic gastritis was revised, and the visual scale grading was incorporated. According to the Updated Sydney System Classification, atrophic gastritis is categorized into multifocal (H. pylori, environmental factors, specific diet and corpus-predominant (autoimmune. Since metaplasia is a key histological characteristic in patients with atrophic gastritis, it has been recommended to use the word “metaplastic” in both variants of atrophic gastritis: autoimmune metaplastic atrophic gastritis (AMAG and environmental metaplastic atrophic gastritis. Although there are many overlaps in the course of the disease and distinction between those two entities may be challenging, the aim of this review article was to describe the etiology, epidemiology, pathogenesis, diagnosis, clinical manifestations and treatment in patients with AMAG. However, it is important to mention that H. pylori is the most common etiologic factor for the development of gastritis in the world. Keywords: autoimmune gastritis, pernicious anemia, gastric carcinoid

  3. Immunoglobulin E-Mediated Autoimmunity

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    Marcus Maurer


    Full Text Available The study of autoimmunity mediated by immunoglobulin E (IgE autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP, and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.

  4. Abdominal manifestations of autoimmune disorders

    International Nuclear Information System (INIS)

    Triantopoulou, C.


    Full text: Immunoglobulin G4-related disease was recognized as a systemic disease since various extrapancreatic lesions were observed in patients with autoimmune pancreatitis (AIP). The real etiology and pathogenesis of IgG4-RD is still not clearly understood. Moreover the exact role of IgG4 or IgG4-positive plasma cells in this disease has not yet been elucidated. only some inconsistent biological features such as hypergammaglobulinemia or hypocomplementemia support the autoimmune nature of the disease process. various names have been ascribed to this clinicopathological entity including IgG4-related sclerosing disease, IgG4-related systemic sclerosing disease, IgG4-related disease, IgG4-related autoimmune disease, hyper-IgG4 disease and IgG4-related systemic disease. The extrapancreatic lesions of IgG4-RD also exhibit the same characteristic histologic features including dense lymphoplasmacytic infiltrate, massive storiform fibrosis, and obliterative phlebitis as seen in IgG4-related pancreatitis. Abdominal manifestations include the following organs/systems: Bile ducts: Sclerosing cholangitis; Gallbladder and liver: Acalculous sclerosis cholecytitis with diffuse wall thickening; hepatic inflammatory pseudotumorts; Kidneys: round or wedge-shaped renal cortical nodules, peripheral cortical; lesions, mass like lesions or renal pelvic involvement; Prostate, urethra, seminal vesicle, vas deferens, uterine cervix; Autoimmune prostatitis; Retroperitoneum: Retroperitoneal fibrosis. thin or mildly thick homogeneous soft tissue lesion surrounding the abdominal aorta and its branches but also bulky masses causing hydronephroureterosis; Mesentery: Sclerosing mesenteritis usually involving the root of the mesentery; Bowel: Inflammatory bowel diseases mimicking Crohn’s disease or ulcerative colitis. various types of sclerosing nodular lesions of the bowel wall; Stomach: Gastritis, gastric ulcers and focal masses mimicking submucosal tumor; omentum: Infiltration mimicking

  5. Autoimmune Cytopenias In Common Variable Immunodeficiency (CVID

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    Roshini Sarah Abraham


    Full Text Available Common variable immunodeficiency (CVID is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20-50%(Chapel et al., 2008;Cunningham-Rundles, 2008, autoimmune cytopenias are by far the most common occurring variably in 4-20% (Michel et al., 2004;Chapel et al., 2008 of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia and neutropenia. While it may seem paradoxical prima facie that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID.

  6. Endocrine autoimmune disease: genetics become complex. (United States)

    Wiebolt, Janneke; Koeleman, Bobby P C; van Haeften, Timon W


    The endocrine system is a frequent target in pathogenic autoimmune responses. Type 1 diabetes and autoimmune thyroid disease are the prevailing examples. When several diseases cluster together in one individual, the phenomenon is called autoimmune polyglandular syndrome. Progress has been made in understanding the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases such as autoimmune polyglandular syndrome type 1, immunodysregulation, polyendocrinopathy, enteropathy, X-linked and primary immune deficiencies helped uncover the role of key regulators in the preservation of immune tolerance. Alleles of the major histocompatibility complex have been known to contribute to the susceptibility to most forms of autoimmunity for more than 3 decades. Furthermore, sequencing studies revealed three non-major histocompatibility complex loci and some disease specific loci, which control T lymphocyte activation or signalling. Recent genome-wide association studies (GWAS) have enabled acceleration in the identification of novel (non-HLA) loci and hence other relevant immune response pathways. Interestingly, several loci are shared between autoimmune diseases, and surprisingly some work in opposite direction. This means that the same allele which predisposes to a certain autoimmune disease can be protective in another. Well powered GWAS in type 1 diabetes has led to the uncovering of a significant number of risk variants with modest effect. These studies showed that the innate immune system may also play a role in addition to the adaptive immune system. It is anticipated that next generation sequencing techniques will uncover other (rare) variants. For other autoimmune disease (such as autoimmune thyroid disease) GWAS are clearly needed. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

  7. Autonomic cardiac innervation (United States)

    Hasan, Wohaib


    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

  8. Multiple Autoimmune Syndromes Associated with Psoriasis: A Rare Clinical Presentation

    Directory of Open Access Journals (Sweden)

    Sadia Masood


    Full Text Available Autoimmune diseases are known to have association with each other but it is very rare to see multiple autoimmune diseases in one patient. The combination of at least three autoimmune diseases in the same patient is referred to as multiple autoimmune syndrome. The case we are reporting features multiple autoimmune syndrome with five different conditions. The patient had type 1 diabetes mellitus, autoimmune hemolytic anemia, systemic lupus erythematosus, vitiligo, and psoriasis. Psoriasis has rarely been reported previously under the spectrum of autoimmune syndrome. Although the relationship of autoimmune conditions with each other has been explored in the past, this case adds yet another dimension to the unique evolution of autoimmune pathologies. The patient presented with a combination of five autoimmune diseases, which makes it consistent type three multiple autoimmune syndromes with the addition of psoriasis. The current case is unique in this aspect that the combination of these five autoimmune disorders has never been reported in the past.

  9. Cystic Lesions in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Macarena Gompertz


    Full Text Available Autoimmune pancreatitis (AIP can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases.

  10. Autoimmune diseases in adults with atopic dermatitis

    DEFF Research Database (Denmark)

    Andersen, Yuki M.F.; Egeberg, Alexander; Gislason, Gunnar H.


    Background An increased susceptibility to autoimmune disease has been shown in patients with atopic dermatitis (AD), but data remain scarce and inconsistent. Objective We examined the co-occurrence of selected autoimmune diseases in adult patients with AD. Methods Nationwide health registers were...

  11. Genetics Home Reference: autoimmune Addison disease (United States)

    ... common in particular ethnic groups? Genetic Changes The cause of autoimmune Addison disease is complex and not completely understood. A combination ... is not caused by an autoimmune reaction. Other causes include infections that ... adrenal glands. Addison disease can also be one of several features of ...

  12. Interferon-¿ regulates oxidative stress during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C.; Penkowa, Milena; Saez-Torres, I.


    Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress......Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress...

  13. TRPM8 mechanism of autonomic nerve response to cold in respiratory airway

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    Wang Cong-Yi


    Full Text Available Abstract Breathing cold air without proper temperature exchange can induce strong respiratory autonomic responses including cough, airway constriction and mucosal secretion, and can exacerbate existing asthma conditions and even directly trigger an asthma attack. Vagal afferent fiber is thought to be involved in the cold-induced respiratory responses through autonomic nerve reflex. However, molecular mechanisms by which vagal afferent fibers are excited by cold remain unknown. Using retrograde labeling, immunostaining, calcium imaging, and electrophysiological recordings, here we show that a subpopulation of airway vagal afferent nerves express TRPM8 receptors and that activation of TRPM8 receptors by cold excites these airway autonomic nerves. Thus activation of TRPM8 receptors may provoke autonomic nerve reflex to increase airway resistance. This putative autonomic response may be associated with cold-induced exacerbation of asthma and other pulmonary disorders, making TRPM8 receptors a possible target for prevention of cold-associated respiratory disorders.

  14. Monogenic autoimmune diseases of the endocrine system. (United States)

    Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E


    The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Autoimmune diseases in women with Turner's syndrome

    DEFF Research Database (Denmark)

    Jørgensen, Kristian T; Rostgaard, Klaus; Bache, Iben


    OBJECTIVE: In terms of number of X chromosomes, women with Turner's syndrome cytogenetically resemble men. An increased risk of autoimmune diseases has been observed among women with Turner's syndrome. This study was undertaken to investigate whether the autoimmune disease profile in women...... with Turner's syndrome is characterized by diseases with a female or male predominance. METHODS: Using the Danish Cytogenetic Central Register, the Danish National Patient Register, and the Danish Civil Registration System, we estimated relative risk of 46 different autoimmune diseases in a cohort of 798...... Danish women with Turner's syndrome followed up for 12,461 person-years between 1980 and 2004. Standardized incidence ratios (SIRs) of first hospitalization for autoimmune disease and 95% confidence intervals (95% CIs) were used as measures of relative risk. RESULTS: The overall risk of autoimmune...

  16. A 41-year-old man with polyarthritis and severe autonomic neuropathy

    Directory of Open Access Journals (Sweden)

    Matthew E Bourcier


    Full Text Available Matthew E Bourcier, Aaron I VinikEastern Virginia Medical School, Norfolk, VA, USAAbstract: Orthostasis due to autonomic neuropathy can cause severe debilitation and prove refractory to treatment. This report describes a case of severe sympathetic and parasympathetic autonomic dysfunction as a consequence of acetylcholine receptor antibodies and Sjogren’s syndrome. Symptomatic management, plasma fluid expanders, and IVIG therapy failed to offer a salutary response to the condition. Etanercept therapy provided improvement of the orthostasis and autonomic function measured as high and low frequency respiratory effects on heart rate variability as well as enhancement of skin blood flow using Laser Doppler. It would be of considerable interest to determine the effectiveness of etanercept in other autoimmune neuropathies.Keywords: autonomic neuropathy, etanercept, IntraEpidermal Nerve Fibers (IENF, acetylcholine receptor antibodies, laser doppler skin blood flow, orthostasis

  17. End-point effector stress mediators in neuroimmune interactions: their role in immune system homeostasis and autoimmune pathology. (United States)

    Dimitrijevic, Mirjana; Stanojevic, Stanislava; Kustrimovic, Natasa; Leposavic, Gordana


    Much evidence has identified a direct anatomical and functional link between the brain and the immune system, with glucocorticoids (GCs), catecholamines (CAs), and neuropeptide Y (NPY) as its end-point mediators. This suggests the important role of these mediators in immune system homeostasis and the pathogenesis of inflammatory autoimmune diseases. However, although it is clear that these mediators can modulate lymphocyte maturation and the activity of distinct immune cell types, their putative role in the pathogenesis of autoimmune disease is not yet completely understood. We have contributed to this field by discovering the influence of CAs and GCs on fine-tuning thymocyte negative selection and, in particular, by pointing to the putative CA-mediated mechanisms underlying this influence. Furthermore, we have shown that CAs are implicated in the regulation of regulatory T-cell development in the thymus. Moreover, our investigations related to macrophage biology emphasize the complex interaction between GCs, CAs and NPY in the modulation of macrophage functions and their putative significance for the pathogenesis of autoimmune inflammatory diseases.

  18. The Putative Son's Attractiveness Alters the Perceived Attractiveness of the Putative Father. (United States)

    Prokop, Pavol


    A body of literature has investigated female mate choice in the pre-mating context (pre-mating sexual selection). Humans, however, are long-living mammals forming pair-bonds which sequentially produce offspring. Post-mating evaluations of a partner's attractiveness may thus significantly influence the reproductive success of men and women. I tested herein the theory that the attractiveness of putative sons provides extra information about the genetic quality of fathers, thereby influencing fathers' attractiveness across three studies. As predicted, facially attractive boys were more frequently attributed to attractive putative fathers and vice versa (Study 1). Furthermore, priming with an attractive putative son increased the attractiveness of the putative father with the reverse being true for unattractive putative sons. When putative fathers were presented as stepfathers, the effect of the boy's attractiveness on the stepfather's attractiveness was lower and less consistent (Study 2). This suggests that the presence of an attractive boy has the strongest effect on the perceived attractiveness of putative fathers rather than on non-fathers. The generalized effect of priming with beautiful non-human objects also exists, but its effect is much weaker compared with the effects of putative biological sons (Study 3). Overall, this study highlighted the importance of post-mating sexual selection in humans and suggests that the heritable attractive traits of men are also evaluated by females after mating and/or may be used by females in mate poaching.

  19. Management of Autoimmune Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Batool F. Kirmani


    Full Text Available Status epilepticus is a neurological emergency with increased morbidity and mortality. Urgent diagnosis and treatment are crucial to prevent irreversible brain damage. In this mini review, we will discuss the recent advances in the diagnosis and treatment of autoimmune status epilepticus (ASE, a rare form of the disorder encountered in the intensive care unit. ASE can be refractory to anticonvulsant therapy and the symptoms include subacute onset of short-term memory loss with rapidly progressive encephalopathy, psychiatric symptoms with unexplained new-onset seizures, imaging findings, CSF pleocytosis, and availability of antibody testing makes an earlier diagnosis of ASE possible. Neuroimmunomodulatory therapies are the mainstay in the treatment of ASE. The goal is to maximize the effectiveness of anticonvulsant agents and find an optimal combination of therapies while undergoing immunomodulatory therapy to reduce morbidity and mortality.

  20. Helminth Immunomodulation in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    John J. Miles


    Full Text Available Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating “talents” of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models and clinical trials and discuss what is known on mechanisms of action. We also highlight current progress in characterizing promising new immunomodulatory molecules found in excretory/secretory products of helminths and their potential use as immunotherapies for acute and chronic inflammatory diseases.

  1. Antiretinal antibody- proven autoimmune retinopathy

    Directory of Open Access Journals (Sweden)

    Sharanya Abraham


    Full Text Available A young female presented with bilateral subacute onset of progressive decrease in night vision and reduced peripheral field of vision. The short duration and rapid progression of symptoms along with the lack of family history of night blindness prompted a diagnosis of autoimmune retinopathy (AIR. Fundus fluorescein angiography, optical coherence tomography, visual fields, and electroretinogram were suggestive of AIR. A differential diagnosis of retinitis pigmentosa (RP was also made. Antiretinal autoantibodies were detected in the blood sample. Treatment was with oral steroids and subsequently oral immunosuppressive agents. Visual acuity was maintained, fundus examination reverted to normal, and investigations repeated at every visit were stable with improvement in visual fields. Our case suggests that AIR, if diagnosed early and treated appropriately, may have a good outcome and should be considered in patients with an atypical presentation of RP.

  2. [Multiorgan autoimmune syndrome: case report]. (United States)

    Ghiringhelli, Paolo; Chelazzi, Paolo; Chelazzi, Giovanni; Bellintani, Claudio; Rania, Simone


    The present case report refers to a multiorgan autoimmune disease manifesting following thymectomy performed for a benign thymoma. This disease is characterized by hypothyroidism, severe myasthenia, polymyositis and alopecia which are organ-specific diseases probably with a different time of onset but which are all an expression of the same immunopathologic process occurring in individuals who have a genetic predisposition. Characteristic of the present case is not only the association of the different immunopathologic clinical pictures but also the rather difficult differential diagnosis between a hypothyroidism-related myopathy and polymyositis. It was possible to formulate the diagnosis by integrating the results of clinical and laboratory evaluation with the therapeutic outcome. The onset of the syndrome was attributed to the withdrawal, following surgery, of the inhibitory effects of the thymoma on some clones of autoreactive lymphocytes.

  3. Insulin autoimmune syndrome: case report

    Directory of Open Access Journals (Sweden)

    Rodrigo Oliveira Moreira

    Full Text Available CONTEXT: Insulin autoimmune syndrome (IAS, Hirata disease is a rare cause of hypoglycemia in Western countries. It is characterized by hypoglycemic episodes, elevated insulin levels, and positive insulin antibodies. Our objective is to report a case of IAS identified in South America. CASE REPORT: A 56-year-old Caucasian male patient started presenting neuroglycopenic symptoms during hospitalization due to severe trauma. Biochemical evaluation confirmed hypoglycemia and abnormally high levels of insulin. Conventional imaging examinations were negative for pancreatic tumor. Insulin antibodies were above the normal range. Clinical remission of the episodes was not achieved with verapamil and steroids. Thus, a subtotal pancreatectomy was performed due to the lack of response to conservative treatment and because immunosuppressants were contraindicated due to bacteremia. Histopathological examination revealed diffuse hypertrophy of beta cells. The patient continues to have high insulin levels but is almost free of hypoglycemic episodes.

  4. Adaptive immunity in autoimmune hepatitis. (United States)

    Longhi, Maria Serena; Ma, Yun; Mieli-Vergani, Giorgina; Vergani, Diego


    The histological lesion of interface hepatitis, with its dense portal cell infiltrate consisting of lymphocytes, monocytes/macrophages and plasma cells, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of autoimmune hepatitis (AIH). Immunohistochemical studies, focused on the phenotype of inflammatory cells infiltrating the liver parenchyma, have shown a predominance of alphabeta-T cells. Amongst these cells, the majority have been CD4 helper/inducers, while a sizeable minority have consisted of CD8 cytotoxic/suppressors. Lymphocytes on non-T cell lineage included natural killer cells, monocytes/macrophages and B lymphocytes. For autoimmunity to arise, the self-antigenic peptide, embraced by an human leukocyte antigen (HLA) class II molecule, must be presented to an uncommitted T helper (T(H)0) lymphocyte by professional antigen-presenting cells. Once activated and according to the presence in the milieu of interleukin 12 (IL-12) or IL-4, T(H)0 lymphocytes can differentiate into T(H)1 cells, which are pivotal to macrophage activation; enhance HLA class I expression, rendering liver cells vulnerable to CD8 T-cell attack; and induce HLA class II expression on hepatocytes; or they can differentiate into T(H)2 cells, which produce IL-4, IL-10 and IL-13, cytokines favouring autoantibody production by B lymphocytes. Autoantigen recognition is tightly controlled by regulatory mechanisms, such as those exerted by CD4+CD25(high) regulatory T cells. Numerical and functional regulatory T cell impairment characterises AIH and permits the perpetuation of effector immune responses with ensuing persistent liver destruction. Advances in the study of autoreactive T cells stem mostly from AIH type 2, where the main autoantigen, cytochrome P450IID6 (CYP2D6), is known to enable characterisation of antigen-specific immune responses. Copyright 2010 S. Karger AG, Basel.

  5. Overview of the Autonomic Nervous System (United States)

    ... be reversible or progressive. Anatomy of the autonomic nervous system The autonomic nervous system is the part of ... organs they connect with. Function of the autonomic nervous system The autonomic nervous system controls internal body processes ...

  6. Cutting-edge issues in autoimmune orchitis. (United States)

    Silva, Clovis A; Cocuzza, Marcello; Borba, Eduardo F; Bonfá, Eloísa


    Autoimmune orchitis is a relevant cause of decreased fecundity in males, and it is defined as a direct aggression to the testis with the concomitant presence of anti-sperm antibodies (ASA). The presence of these specific antibodies has been observed in approximately 5-12% of infertile male partners. Primary autoimmune orchitis is defined by isolated infertility with ASA but without evidence of a systemic disease. Secondary causes of orchitis and/or testicular vasculitis are uniformly associated with autoimmune diseases, mainly in primary vasculitis such as polyarteritis nodosa, Behçet's disease, and Henoch-Schönlein purpura. The overall frequencies of acute orchitis and ASA in rheumatic diseases are 2-31% and 0-50%, respectively. The pathogenesis of primary/secondary autoimmune orchitis is not completely understood but probably involves the access of immune cells to the testicular microenvironment due to inflammation, infection or trauma, leading to apoptosis of spermatocytes and spermatids. Glucocorticoids and immunosuppressive drugs are indicated in autoimmune orchitis-associated active systemic autoimmune diseases. However, there are no standardized treatment options, and the real significance of ASA in infertile men is still controversial. Assisted reproductive technologies such as intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection (ICSI) are therapeutic options for male infertility associated with these autoantibodies. ICSI is considered to be the best choice for patients with severe sperm autoimmunity, particularly in males with low semen counts or motility.

  7. Diagnosis and classification of autoimmune orchitis. (United States)

    Silva, C A; Cocuzza, M; Carvalho, J F; Bonfá, E


    Autoimmune orchitis is characterized by testis inflammation and the presence of specific antisperm antibodies (ASA). It is classified in two categories. Primary autoimmune orchitis is defined by infertility and asymptomatic orchitis associated with ASA (100%) directed to the basement membrane or seminiferous tubules in infertile men, without any systemic disease and usually asymptomatic. Secondary autoimmune orchitis is characterized by symptomatic orchitis and/or testicular vasculiti`s associated with a systemic autoimmune disease, particularly vasculitis. These patients typically demonstrate testicular pain, erythema and/or swelling. ASA in secondary autoimmune orchitis have been reported in up to 50% of patients, especially in systemic lupus erythematosus patients. The pathogenesis of primary as well as secondary autoimmune orchitis is still unknown. Although the etiology is likely to be multifactorial, testicular inflammation, infection or trauma may induce T cell response with pro-inflammatory cytokine production with a consequent blood-testis-barrier permeability alteration, ASA production and apoptosis of spermatocytes and spermatids. ASA is known to cause immobilization and/or agglutination of spermatozoa, which may block sperm-egg interaction resulting in infertility. Assisted reproduction has been used as an efficient option in primary cases and immunosuppressive therapy for secondary autoimmune orchitis, although there is no double-blind, randomized trial to confirm the efficacy of any treatment regimens for these conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Autonomous Forest Fire Detection

    NARCIS (Netherlands)

    Breejen, E. den; Breuers, M.; Cremer, F.; Kemp, R.A.W.; Roos, M.; Schutte, K.; Vries, J.S. de


    Forest fire detection is a very important issue in the pre-suppression process. Timely detection allows the suppression units to reach the fire in its initial stages and this will reduce the suppression costs considerably. The autonomous forest fire detection principle is based on temporal contrast

  9. Experimental Autonomous Vehicle Systems

    DEFF Research Database (Denmark)

    Ravn, Ole; Andersen, Nils Axel


    The paper describes the requirements for and a prototype configuration of a software architecture for control of an experimental autonomous vehicle. The test bed nature of the system is emphasised in the choice of architecture making re-configurability, data logging and extendability simple...

  10. Towards autonomous vehicles. (United States)


    We are moving towards an age of autonomous vehicles. Cycles of innovation initiated in the public and private sectors : have led one into another since the 1990s; and out of these efforts have sprung a variety of Advanced Driver Assistance : Systems ...

  11. ADAM: ADaptive Autonomous Machine

    NARCIS (Netherlands)

    van Oosten, Daan C.; Nijenhuis, Lucas F.J.; Bakkers, André; Vervoort, Wiek


    This paper describes a part of the development of an adaptive autonomous machine that is able to move in an unknown world extract knowledge out of the perceived data, has the possibility to reason, and finally has the capability to exchange experiences and knowledge with other agents. The agent is

  12. No association of psoriasis with autoimmune thyroiditis. (United States)

    Vassilatou, E; Papadavid, E; Papastamatakis, P; Alexakos, D; Koumaki, D; Katsimbri, P; Hadjidakis, D; Dimitriadis, G; Rigopoulos, D


    Common autoimmune diseases tend to coexist in the same patients. Few studies have examined the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with inconsistent results. To investigate the prevalence of autoimmune thyroiditis in psoriatic patients with or without PsA, living in an iodine-sufficient area. We studied prospectively, 114 psoriatic patients with disease duration of 5-38 years, 30 of them with PsA, and 286 age- and body mass index (BMI)-matched subjects without psoriasis or known thyroid disease or autoimmune disease. A detailed medical history was obtained from all participants and clinical examination and laboratory evaluation was performed. Psoriasis severity was assessed with Psoriasis Area and Severity Index (PASI). Autoimmune thyroiditis was defined by the presence of positive autoantibodies to thyroid peroxidase and/or thyroglobulin. There was no difference in the prevalence of autoimmune thyroiditis between psoriatic patients and controls (20.2% vs. 19.6%). The prevalence of autoimmune thyroiditis in male and female psoriatic patients was similar (9.6% and 10.5% respectively), in contrast to the increased, as expected, prevalence in female vs. male controls (14.7% vs. 4.9%, P thyroiditis were similar in psoriatic patients and controls (7.9% and 7.0% respectively). Autoimmune thyroiditis in psoriatic patients was not related with age of psoriasis onset, psoriasis duration, PASI score, PsA and obesity. These data support that psoriatic patients with or without PsA do not have an increased risk for autoimmune thyroiditis. © 2016 European Academy of Dermatology and Venereology.

  13. Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C; Carrasco, J; Hidalgo, J


    Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein......-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflammatory cytokine, in the control of metallothioneins expression...

  14. Eating Disorders, Autoimmune, and Autoinflammatory Disease

    DEFF Research Database (Denmark)

    Zerwas, Stephanie; Larsen, Janne Tidselbak; Petersen, Liselotte


    higher hazards of eating disorders for children and adolescents with autoimmune or autoinflammatory diseases: 36% higher hazard for anorexia nervosa, 73% for bulimia nervosa, and 72% for an eating disorder not otherwise specified. The association was particularly strong in boys. Parental autoimmune...... or autoinflammatory disease history was associated with significantly increased odds for anorexia nervosa (odds ratio [OR] = 1.13, confidence interval [CI] = 1.01-1.25), bulimia nervosa (OR = 1.29; CI = 1.08-1.55) and for an eating disorder not otherwise specified (OR = 1.27; CI = 1.13-1.44). CONCLUSIONS: Autoimmune...

  15. Retinal phlebitis associated with autoimmune hemolytic anemia. (United States)

    Chew, Fiona L M; Tajunisah, Iqbal


    To describe a case of retinal phlebitis associated with autoimmune hemolytic anemia. Observational case report. A 44-year-old Indian man diagnosed with autoimmune hemolytic anemia presented with a 1-week history of blurred vision in both eyes. Fundus biomicroscopy revealed bilateral peripheral retinal venous sheathing and cellophane maculopathy. Fundus fluorescent angiogram showed bilateral late leakage from the peripheral venous arcades and submacular fluid accumulation. The retinal phlebitis resolved following a blood transfusion and administration of systemic steroids. Retinopathy associated with autoimmune hemolytic anemia is not well known. This is thought to be the first documentation of retinal phlebitis occurring in this condition.

  16. Presence of Autoimmune Antibody in Chikungunya Infection

    Directory of Open Access Journals (Sweden)

    Wirach Maek-a-nantawat


    Full Text Available Chikungunya infection has recently re-emerged as an important arthropod-borne disease in Thailand. Recently, Southern Thailand was identified as a potentially endemic area for the chikungunya virus. Here, we report a case of severe musculoskeletal complication, presenting with muscle weakness and swelling of the limbs. During the investigation to exclude autoimmune muscular inflammation, high titers of antinuclear antibody were detected. This is the report of autoimmunity detection associated with an arbovirus infection. The symptoms can mimic autoimmune polymyositis disease, and the condition requires close monitoring before deciding to embark upon prolonged specific treatment with immunomodulators.

  17. Identification and characterization of putative conserved IAM ...

    African Journals Online (AJOL)

    Available putative AMI sequences from a wide array of monocot and dicot plants were identified and the phylogenetic tree was constructed and analyzed. We identified in this tree, a clade that contained sequences from species across the plant kingdom suggesting that AMI is conserved and may have a primary role in plant ...

  18. Toddlers' Duration of Attention toward Putative Threat (United States)

    Kiel, Elizabeth J.; Buss, Kristin A.


    Although individual differences in reactions to novelty in the toddler years have been consistently linked to risk of developing anxious behavior, toddlers' attention toward a novel, putatively threatening stimulus while in the presence of other enjoyable activities has rarely been examined as a precursor to such risk. The current study examined…

  19. liver cirrhosis from autoimmune hepatitis in a nigerian woman

    African Journals Online (AJOL)

    like autoimmune thyroiditis, celiac disease and ulcerative colitis, with about 25% having cirrhosis at ... to immunosuppressive therapy. Keywords: Autoimmune hepatitis, Autoimmune liver disease, Chronic liver disease, Nigeria ... who is also exposed to environmental triggering factors.2,5,8 Subsequently, the autoimmune.

  20. Catecholamines and diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J


    In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity...... of plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors......) are not altered in circulating blood cells in diabetic autonomic neuropathy. Thus, a generalized up-regulation of adrenoceptors does not occur in diabetic autonomic neuropathy....

  1. Autoimmune pancreatitis : Diagnostic and immunological aspects

    NARCIS (Netherlands)

    M.J. van Heerde (Marianne)


    textabstractAutoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic fibro- inflammatory disease, characterized by infiltration with lymphoplasmacytic cells and extensive fibrosis, which leads to morphological changes (swelling, mass forming) and organ dysfunction. Often, but

  2. Th17 Response and Inflammatory Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Janelle C. Waite


    Full Text Available The proinflammatory activity of T helper 17 (Th17 cells can be beneficial to the host during infection. However, uncontrolled or inappropriate Th17 activation has been linked to several autoimmune and autoinflammatory pathologies. Indeed, preclinical and clinical data show that Th17 cells are associated with several autoimmune diseases such as arthritis, multiple sclerosis, psoriasis, and lupus. Furthermore, targeting the interleukin-17 (IL-17 pathway has attenuated disease severity in preclinical models of autoimmune diseases. Interestingly, a recent report brings to light a potential role for Th17 cells in the autoinflammatory disorder adult-onset Still's disease (AOSD. Whether Th17 cells are the cause or are directly involved in AOSD remains to be shown. In this paper, we discuss the biology of Th17 cells, their role in autoimmune disease development, and in AOSD in particular, as well as the growing interest of the pharmaceutical industry in their use as therapeutic targets.

  3. Autoimmune Response Confers Decreased Cardiac Function in ...

    African Journals Online (AJOL)

    inflammatory response; rather, autoimmune response would keep affecting decreased heart function in. RHD patients who ... untreated children. Nearly 30 - 45 % of the affected children could ..... Technology Department of Anhui Province (PR.

  4. Auto-immune hepatitis following delivery. (United States)

    Saini, Vandana; Gupta, Mamta; Mishra, S K


    Auto-immune hepatitis first presenting in the early postpartum period is rare. Immunosuppressive effects of pregnancy result in delayed manifestation of auto-immune hepatitis, and in established cases, the spontaneous improvements are there. Auto-immune hepatitis should be considered in the differential diagnosis of liver dysfunction first presenting in the early postpartum period. A case of postpartum hepatitis of auto-immune aetiology is being presented here. It is disease of unknown aetiology, characterised by inflammation of liver (as evidenced by raised serum transaminases, presence of interface hepatitis on histological examination), hypergammaglobulinaemia (> 1.5 times normal), presence of auto-antibodies [(antinuclear antibodies (ANA)], smooth muscle antibody (SMA) and antibody to liver-kidney microsome type 1 (LKM1) in the absence of viral markers ie, hepatitis B (HBsAg) and C (AntiHCV) and excellent response to corticosteroid therapy.

  5. Humanized in vivo Model for Autoimmune Diabetes

    National Research Council Canada - National Science Library

    Nepom, Gerald T; Gebe, John A


    The CD4+ T cell response is critical for cellular autoimmunity in human T1D, but incomplete understanding of issues of specific cell frequency, avidity, function, and correlation with disease status presents...

  6. [Autoimmune diseases of the thyroid gland]. (United States)

    Allelein, S; Feldkamp, J; Schott, M


    Autoimmune diseases of the thyroid gland are considered to be the most frequent cause of thyroid gland disorders. Autoimmune thyroid diseases consist of two subgroups: autoimmune thyroiditis (AIT) and Graves' disease. The AIT is the most common human autoimmune disease. Infiltration of the thyroid gland with cytotoxic T‑cells can lead to an initial thyrotoxicosis und during the course to hypothyroidism due to destruction of the thyroid gland. Substitution with Levothyroxine is indicated for manifest hypothyroidism and subclinical hypothyroidism with increased thyroid antibodies with the intention of normalizing the serum thyroid stimulating hormone (TSH). Graves' disease is characterized by the appearance of stimulating TSH receptor antibodies leading to hyperthyroidism. Endocrine ophthalmopathy may also occur. Ablative therapy with radioiodine therapy or thyroidectomy is administered to patients with Graves' disease without remission after at least 1 year of antithyroid drug therapy.

  7. Anetoderma: Is It a Sign of Autoimmunity?

    Directory of Open Access Journals (Sweden)

    Hessa Al Buainain


    Full Text Available Anetoderma is a rare elastolytic disorder characterized by circumscribed areas of flaccid skin due to the loss of elastic tissue in the dermis. Primary anetoderma is frequently observed in patients with autoimmune diseases or abnormalities especially with antiphospholipid antibodies with or without antiphospholipid syndrome. In this case report we discuss a patient with primary anetoderma with positive antithyroid peroxidase antibodies, which is consistent with autoimmune thyroiditis.

  8. Treatment of patients with severe autoimmune hepatitis

    DEFF Research Database (Denmark)

    Larsen, Finn Stolze


    Autoimmune hepatitis (AIH) is a progressive inflammatory diseases of unknown origin that is characterised by a necro-inflammatory and fibrotic process and may result in liver failure or uncompensated liver cirrhosis. Normally AIH is responsive to immunosuppressive therapy, and treatment aims...... and tacrolimus) might salvage patients from transplantation. Mycophenolate mofetil may also improve liver tests and reduce the requirement for corticosteroids. Besides, sirolimus is effective for treatment of de novo autoimmune hepatitis that sometimes develops after liver transplantation. Initial experience...

  9. Regulatory T-cells and autoimmunity.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh


    Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.

  10. Autoimmune connective tissue diseases and vaccination

    Directory of Open Access Journals (Sweden)

    Ewa Więsik-Szewczyk


    Full Text Available The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently Epsteinasensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

  11. NK cell autoreactivity and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Alessandro ePoggi


    Full Text Available Increasing evidences have pointed out the relevance of Natural Killer (NK cells in organ specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands upregulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILC, comprising the classical CD56+ NK cells, have a role in maintaining or alterating tissue homeostasis secreting protective and/or proinflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular matrix components and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity.

  12. Thyroid Autoimmunity in Girls with Turner Syndrome. (United States)

    Witkowska-Sędek, Ewelina; Borowiec, Ada; Kucharska, Anna; Chacewicz, Karolina; Rumińska, Małgorzata; Demkow, Urszula; Pyrżak, Beata


    Turner syndrome is associated with increased incidence of autoimmune diseases, especially those of the thyroid gland. The aim of this study was to assess the prevalence of thyroid autoimmunity among pediatric patients with Turner syndrome. The study was retrospective and included 41 girls with Turner syndrome aged 6-18 years. Free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO-Ab) antibodies, anti-thyroglobulin (TG-Ab) antibodies, and karyotype were investigated. The correlation between karyotype and incidence of thyroid autoimmunity was also examined. Eleven patients (26.8%) were positive for TPO-Ab and/or TG-Ab. Three girls from that subgroup were euthyroid, 5 had subclinical hypothyroidism, and 3 were diagnosed with overt hypothyroidism. Out of these 11 patients affected by thyroid autoimmunity, 6 girls had mosaic karyotype with X-isochromosome (n = 4) or with deletions (n = 2), and 5 had the 45,X karyotype. The study findings confirmed a high incidence of thyroid autoimmunity in girls with Turner syndrome, but we failed to observe an association between the incidence of thyroid autoimmunity and karyotype. We conclude that it is important to monitor thyroid function in patients with Turner syndrome because they are prone to develop hypothyroidism.

  13. Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders. (United States)

    Ordookhani, Arash; Burman, Kenneth D


    There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted.

  14. Autoimmune liver disease in Noonan Syndrome. (United States)

    Loddo, Italia; Romano, Claudio; Cutrupi, Maria Concetta; Sciveres, Marco; Riva, Silvia; Salpietro, Annamaria; Ferraù, Valeria; Gallizzi, Romina; Briuglia, Silvana


    Noonan Syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Autoimmune Hepatitis (AIH) is a cryptogenic, chronic and progressive necroinflammatory liver disease. Common features of AIH are hypergammaglobulinemia (IgG), presence of circulating autoantibodies, histological picture of interface hepatitis and response to immunosuppressant drugs. Conventional treatment with Prednisone and Azathioprine is effective in most patients. We describe the case of a 6 years-old girl with Noonan Syndrome and Autoimmune Hepatitis type 1. Molecular analysis of PTPN11 gene showed heterozygous mutation c.923A>G (Asn308Ser) in exon 8. Though association between NS and autoimmune disorders is known, this is the second case of association between Noonan Syndrome and Autoimmune Hepatitis type 1 described in literature. In the management of NS, an accurate clinical evaluation would be recommended. When there is a clinical suspicion of autoimmune phenomena, appropriate laboratory tests should be performed with the aim of clarifying whether the immune system is involved in NS. We think that autoimmunity represents a characteristic of NS, even if the etiopathogenesis is still unknown. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. [Autoimmune thyroiditis and thyroid cancer]. (United States)

    Krátký, Jan; Jiskra, Jan


    Association between autoimmune thyroiditis (CLT) and thyroid cancer remains not clear. Although both diseases often occur simultaneously in histological samples, it is not yet clear whether CLT can be regarded as a risk factor for thyroid malignancy. This review focus on the known epidemiological and molecular genetics links between both diseases. Most studies have shown a significant association between thyroid cancer and positive antibodies to thyroglobulin and histological evidence of CLT, as well. Both disorders share some risk factors (greater incidence in women, in areas with adequate supply of iodine and in patients after radiotherapy of the neck) and molecular genetics linkage. For example: RET/PTC rearrangements could be more often found in carcinomas associated with CLT, but this mutation could be found in benign lesions such as CLT, as well. CLT seems to be a positive prognostic factor in patients with differentiated thyroid cancer. It is associated with less invasive forms of tumor, lower occurrence of infiltrated lymphatic nodes and a lower risk of recurrence.

  16. Transplantation in autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Marcus Mottershead; James Neuberger


    Liver transplantation remains an effective treatment for those with end-stage disease and with intractable liver-related symptoms.The shortage of organs for transplantation has resulted in the need for rationing.A variety of approaches to selection and allocation have been developed and vary from country to country.The shortage of donors has meant that new approaches have to be adopted to make maximal use of the available organs;these include splitting grafts,use of extended criteria livers,livers from nonheart-beating donors and from living donors.Post transplantation, most patients will need life-long immunosuppression,although a small proportion can have immunosuppression successfully withdrawn.Newer immunosuppressive drugs and different strategies may allow a more targeted approach with a reduction in sideeffects and so improve the patient and graft survival.For autoimmune diseases, transplantation is associated with significant improvement in the quality and length of life.Disease may recur after transplantation and may affect patient and graft survival.

  17. [Autoimmune Associated Encephalitis and Dementia]. (United States)

    Watanabe, Osamu


    Antibodies against various neural surface antigens induce cognitive impairments. Anti-VGKC (voltage gated potassium channel) complex antibodies are well known as one of the causative autoantibodies. An anti-VGKC antibody was identified as the autoantibody in acquired neuromyotonia (Isaacs' syndrome), which causes muscle cramps and difficulty in opening the palm of the hands. However, this antibody also tests positive in autoimmune limbic encephalitis, which has a subacute progress and causes poor memory or epilepsy attacks. Typical cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures. In recent years, the true target antigens of the anti-VGKC antibody of this VGKC limbic encephalitis have been recognized as leucine rich glioma inactivated protein (LGI)-1 and others. These antibodies to amnesia-related LGI-1 in limbic encephalitis neutralize the LGI-1-ADAM22 (an anchor protein) interaction and reduce synaptic AMPA receptors. There have been reports of limbic encephalitis associated with anti-VGKC complex antibodies mimicking Creutzfeldt-Jakob disease (CJD). Less than 2% of the patients with sporadic CJD (sCJD) develop serum anti-VGKC complex antibodies and, when positive, only at low titres. Low titres of these antibodies occur only rarely in suspected patients with sCJD, and when present, should be interpreted with caution.

  18. Autonomous Intersection Management (United States)


    detects that the driver is not slowing sufficiently fast. Jaguar, Honda, and BMW offer similar systems. Nissan and Toyota have recently begun offering...that the driver is not braking hard enough. Both Toyota and BMW are currently selling vehicles that can parallel park completely autonomously, even...other vehicles. The system was tested both in simulation and with a robotic vehicle. This work is sponsored by Toyota , who have also currently have an

  19. Autonomía


    Martínez Muñoz, Juan Antonio


    En este ensayo la noción de autonomía es estudiada de un modo diferente al sentido habitual; sus implicaciones y las contradicciones que encierra, específicamente como sucedáneo de la genuina libertad. El artículo describe el modelo de hombre presupuesto en su uso. Concluye con su inviabilidad para resolver problemas morales y sociales.

  20. Mobile Intelligent Autonomous Systems


    Jitendra R. Raol; Ajith Gopal


    Mobile intelligent autonomous systems (MIAS) is a fast emerging research area. Although it can be regarded as a general R&D area, it is mainly directed towards robotics. Several important subtopics within MIAS research are:(i) perception and reasoning, (ii) mobility and navigation,(iii) haptics and teleoperation, (iv) image fusion/computervision, (v) modelling of manipulators, (vi) hardware/software architectures for planning and behaviour learning leadingto robotic architecture, (vii) ve...

  1. Highly Skilled Autonomous Vehicles


    Manuel Acosta Reche; Stratis Kanarachos; Mike V Blundell


    Recent research suggests that collision mitigation on low grip surfaces might require autonomous vehicles to execute maneuvers such as drift, trail braking or Scandinavian flick. In order to achieve this it is necessary to perceive the vehicle states and their interaction with the environment, and use this information to determine the chassis limits. A first look at the virtual automotive sensing problem is provided, followed by a description of Rally driving modeling approaches. Finally, a c...

  2. Autonomous Underwater Gliders


    Wood,; Stephen,


    Autonomous Underwater Vehicles are only now being marketed as robust commercial vehicles for many industries, and of these vehicles underwater gliders are becoming the new tool for oceanographers. Satellites have provided scientists and marine specialists with measurements of the sea surface such as temperature since the late 1970s, and data via subsurface oceanographic moorings since the 1950's. As stated by David Smeed of the National Oceanography Centre, Southampton, England, that "gliders...

  3. Nature's Autonomous Oscillators (United States)

    Mayr, H. G.; Yee, J.-H.; Mayr, M.; Schnetzler, R.


    Nonlinearity is required to produce autonomous oscillations without external time dependent source, and an example is the pendulum clock. The escapement mechanism of the clock imparts an impulse for each swing direction, which keeps the pendulum oscillating at the resonance frequency. Among nature's observed autonomous oscillators, examples are the quasi-biennial oscillation and bimonthly oscillation of the Earth atmosphere, and the 22-year solar oscillation. The oscillations have been simulated in numerical models without external time dependent source, and in Section 2 we summarize the results. Specifically, we shall discuss the nonlinearities that are involved in generating the oscillations, and the processes that produce the periodicities. In biology, insects have flight muscles, which function autonomously with wing frequencies that far exceed the animals' neural capacity; Stretch-activation of muscle contraction is the mechanism that produces the high frequency oscillation of insect flight, discussed in Section 3. The same mechanism is also invoked to explain the functioning of the cardiac muscle. In Section 4, we present a tutorial review of the cardio-vascular system, heart anatomy, and muscle cell physiology, leading up to Starling's Law of the Heart, which supports our notion that the human heart is also a nonlinear oscillator. In Section 5, we offer a broad perspective of the tenuous links between the fluid dynamical oscillators and the human heart physiology.

  4. Predictive models in the diagnosis and treatment of autoimmune epilepsy. (United States)

    Dubey, Divyanshu; Singh, Jaysingh; Britton, Jeffrey W; Pittock, Sean J; Flanagan, Eoin P; Lennon, Vanda A; Tillema, Jan-Mendelt; Wirrell, Elaine; Shin, Cheolsu; So, Elson; Cascino, Gregory D; Wingerchuk, Dean M; Hoerth, Matthew T; Shih, Jerry J; Nickels, Katherine C; McKeon, Andrew


    To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. We conducted a retrospective study of epilepsy cases at Mayo Clinic (Rochester-MN; Scottsdale-AZ, and Jacksonville-FL) in whom autoimmune encephalopathy/epilepsy/dementia autoantibody testing profiles were requested (06/30/2014-06/30/2016). An Antibody Prevalence in Epilepsy (APE) score, based on clinical characteristics, was assigned to each patient. Among patients who received immunotherapy, a Response to Immunotherapy in Epilepsy (RITE) score was assigned. Favorable seizure outcome was defined as >50% reduction of seizure frequency at the first follow-up. Serum and cerebrospinal fluid (CSF) from 1,736 patients were sent to the Mayo Clinic Neuroimmunology Laboratory for neural autoantibody evaluation. Three hundred eighty-seven of these patients met the diagnostic criteria for epilepsy. Central nervous system (CNS)-specific antibodies were detected in 44 patients. Certain clinical features such as new-onset epilepsy, autonomic dysfunction, viral prodrome, faciobrachial dystonic seizures/oral dyskinesia, inflammatory CSF profile, and mesial temporal magnetic resonance imaging (MRI) abnormalities had a significant association with positive antibody results. A significantly higher proportion of antibody-positive patients had an APE score ≥4 (97.7% vs. 21.6%, p < 0.01). Sensitivity and specificity of an APE score ≥4 to predict presence of specific neural auto-antibody were 97.7% and 77.9%, respectively. In the subset of patients who received immunotherapy (77), autonomic dysfunction, faciobrachial dystonic seizures/oral dyskinesia, early initiation of immunotherapy, and presence of antibodies targeting plasma membrane proteins (cell-surface antigens) were associated with favorable seizure outcome. Sensitivity and specificity of a RITE score ≥7 to predict favorable seizure outcome were 87.5% and 83.8%, respectively. APE and RITE scores can aid diagnosis

  5. Is Thyroid Autoimmunity per se a Determinant of Quality of Life in Patients with Autoimmune Hypothyroidism?

    DEFF Research Database (Denmark)

    Watt, Torquil; Bjørner, Jakob; Grønvold, Mogens


    PURPOSE: To evaluate the relationship between thyroid variables and health-related quality of life (QoL) in patients with autoimmune hypothyroidism, using the thyroid-specific QoL questionnaire ThyPRO. METHODS: In a cross-sectional study, responses to the ThyPRO from 199 outpatients with autoimmune...

  6. Autonomic Neuropathy in Diabetes Mellitus


    Verrotti, Alberto; Prezioso, Giovanni; Scattoni, Raffaella; Chiarelli, Francesco


    Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent ...

  7. Robotics and Autonomous Systems Laboratory (United States)

    Federal Laboratory Consortium — FUNCTION: Provides an environment for developing and evaluating intelligent software for both actual and simulated autonomous vehicles. Laboratory computers provide...

  8. Autonomic Fuselet Specification and Composition

    National Research Council Canada - National Science Library

    Mills, Peter H


    A framework for autonomic fuselet business logic development was developed, using semantic web services and workflow technologies to specify fuselet information needs, to define an executable workflow...

  9. Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults.

    Directory of Open Access Journals (Sweden)

    Magdalena Niegowska

    Full Text Available Latent Autoimmune Diabetes in Adults (LADA is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of type 2 diabetes (T2D with the presence of islet cell antigens detected in type 1 diabetes (T1D. Heterogeneous clinical picture have led to the classification of patients based on the levels of antibodies against glutamic acid decarboxylase 65 (GADA that correlate with clinical phenotypes closer to T1D or T2D when GADA titers are high or low, respectively. To date, LADA etiology remains elusive despite numerous studies investigating on genetic predisposition and environmental risk factors. To our knowledge, this is the first study aimed at evaluation of a putative role played by Mycobacterium avium subsp. paratuberculosis (MAP as an infective agent in LADA pathogenesis. MAP is known to cause chronic enteritis in ruminants and has been associated with autoimmune disorders in humans. We analyzed seroreactivity of 223 Sardinian LADA subjects and 182 healthy volunteers against MAP-derived peptides and their human homologs of proinsulin and zinc transporter 8 protein. A significantly elevated positivity for MAP/proinsulin was detected among patients, with the highest prevalence in the 32-41-year-old T1D-like LADA subgroup, supporting our hypothesis of a possible MAP contribution in the development of autoimmunity.

  10. Assessing Age-Related Etiologic Heterogeneity in the Onset of Islet Autoimmunity

    Directory of Open Access Journals (Sweden)

    Brittni N. Frederiksen


    Full Text Available Type 1 diabetes (T1D, a chronic autoimmune disease, is often preceded by a preclinical phase of islet autoimmunity (IA where the insulin-producing beta cells of the pancreas are destroyed and circulating autoantibodies can be detected. The goal of this study was to demonstrate methods for identifying exposures that differentially influence the disease process at certain ages by assessing age-related heterogeneity. The Diabetes Autoimmunity Study in the Young (DAISY has followed 2,547 children at increased genetic risk for T1D from birth since 1993 in Denver, Colorado, 188 of whom developed IA. Using the DAISY population, we evaluated putative determinants of IA, including non-Hispanic white (NHW ethnicity, maternal age at birth, and erythrocyte membrane n-3 fatty acid (FA levels, for age-related heterogeneity. A supremum test, weighted Schoenfeld residuals, and restricted cubic splines were used to assess nonproportional hazards, that is, an age-related association of the exposure with IA risk. NHW ethnicity, maternal age, and erythrocyte membrane n-3 FA levels demonstrated a significant age-related association with IA risk. Assessing heterogeneity in disease etiology enables researchers to identify associations that may lead to better understanding of complex chronic diseases.

  11. Autoimmune Abnormalities of Postpartum Thyroid Diseases

    Directory of Open Access Journals (Sweden)

    Flavia Di Bari


    Full Text Available The year following parturition is a critical time for the de novo appearance or exacerbation of autoimmune diseases, including autoimmune thyroid disease. The vast majority of postpartum thyroid disease consists of postpartum thyroiditis (PPT and the minority by Graves’ disease and non-autoimmune thyroiditis. PPT has a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review published in 2012. Several factors confer risk for the development of PPT. Typically, the clinical course of PPT is characterized by three phases: thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women will have permanent hypothyroidism. The best humoral marker for predictivity, already during the first trimester of gestation, is considered positivity for thyroperoxidase autoantibodies (TPOAb, though only one-third to half of such TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a recent study on pregnant women with stable dietary habits, we found that the fish consumers had lower rates of positivity (and lower serum levels of both TPOAb and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of other diseases that can be observed in the postpartum period, either autoimmune or non-autoimmune, thyroid or non-thyroid.

  12. Autoimmune hepatitis in Italy: the Bologna experience. (United States)

    Muratori, Paolo; Granito, Alessandro; Quarneti, Chiara; Ferri, Silvia; Menichella, Rita; Cassani, Fabio; Pappas, Georgios; Bianchi, Francesco B; Lenzi, Marco; Muratori, Luigi


    Autoimmune hepatitis affects mainly women. It is subdivided into type 1 and type 2 according to the autoantibody profile and without immunosuppression usually evolves to cirrhosis and end-stage liver failure. We evaluated clinical, biochemical, immunological and genetic features and treatment response of 163 consecutive Italian patients with autoimmune hepatitis. At diagnosis, type 1 autoimmune hepatitis showed more inflamed liver histology and more pronounced cholestasis, whereas type 2 was more common in children. Male and female patients shared similar clinical, biochemical and immunological features. Of 89 patients with 5-year follow-up or longer, 23 patients irrespective of presenting clinical, biochemical and immunological features achieved complete remission (normal transaminases and gammaglobulin levels) which was maintained with minimal steroid dosage; attempt at treatment withdrawal led to disease exacerbation. Complete responders had more often HLA DRB1*0401 (p = 0.011) and their risk of disease progression was lower (p < 0.0001). Type 1 and type 2 autoimmune hepatitis is one and the same disease. Autoimmune hepatitis has similar features in male and female patients. HLA DRB1*0401 positive patients are more likely to achieve complete remission. Continuous low-dose steroids are necessary to maintain remission, significantly reducing the risk of disease progression.

  13. Upper gastrointestinal symptoms in autoimmune gastritis (United States)

    Carabotti, Marilia; Lahner, Edith; Esposito, Gianluca; Sacchi, Maria Carlotta; Severi, Carola; Annibale, Bruno


    Abstract Autoimmune gastritis is often suspected for its hematologic findings, and rarely the diagnosis is made for the presence of gastrointestinal symptoms. Aims of this cross-sectional study were to assess in a large cohort of patients affected by autoimmune gastritis the occurrence and the pattern of gastrointestinal symptoms and to evaluate whether symptomatic patients are characterized by specific clinical features. Gastrointestinal symptoms of 379 consecutive autoimmune gastritis patients were systematically assessed and classified following Rome III Criteria. Association between symptoms and anemia pattern, positivity to gastric autoantibodies, Helicobacter pylori infection, and concomitant autoimmune disease were evaluated. In total, 70.2% of patients were female, median age 55 years (range 17–83). Pernicious anemia (53.6%), iron deficiency anemia (34.8%), gastric autoantibodies (68.8%), and autoimmune disorders (41.7%) were present. However, 56.7% of patients complained of gastrointestinal symptoms, 69.8% of them had exclusively upper symptoms, 15.8% only lower and 14.4% concomitant upper and lower symptoms. Dyspepsia, subtype postprandial distress syndrome was the most represented, being present in 60.2% of symptomatic patients. Univariate and multivariate analyses showed that age gastritis is associated in almost 60% of cases with gastrointestinal symptoms, in particular dyspepsia. Dyspepsia is strictly related to younger age, no smoking, and absence of anemia. PMID:28072728

  14. Autoimmune gastritis: Pathologist’s viewpoint (United States)

    Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo


    Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling. PMID:26576102

  15. PD-1 Checkpoint Inhibitor Associated Autoimmune Encephalitis

    Directory of Open Access Journals (Sweden)

    Stephanie Schneider


    Full Text Available Objective: To report first-hand narrative experience of autoimmune encephalitis and to briefly review currently available evidence of autoimmune encephalitis in cancer patients treated with immune checkpoint inhibitors. Setting: A case study is presented on the management of a patient who developed autoimmune encephalitis during nivolumab monotherapy occurring after 28 weeks on anti-PD-1 monotherapy (nivolumab 3 mg/kg every 2 weeks for non-small cell lung cancer. Results: No substantial improvement was observed by antiepileptic treatment. After administration of 80 mg methylprednisolone, neurologic symptoms disappeared within 24 h and the patient fully recovered. Conclusions: Immune checkpoint inhibitor treatment can lead to autoimmune encephalitis. Clinical trial data indicate a frequency of autoimmune encephalitis of ≥0.1 to <1% with a higher probability during combined or sequential anti-CTLA-4/anti-PD-1 therapy than during anti-PD-1 or anti-PD-L1 monotherapy. Further collection of evidence and translational research is warranted.

  16. Complicating autoimmune diseases in myasthenia gravis: a review (United States)

    Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik


    Abstract Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis. PMID:25915571

  17. Autonomous component carrier selection

    DEFF Research Database (Denmark)

    Garcia, Luis Guilherme Uzeda; Pedersen, Klaus; Mogensen, Preben


    management and efficient system operation. Due to the expected large number of user-deployed cells, centralized network planning becomes unpractical and new scalable alternatives must be sought. In this article, we propose a fully distributed and scalable solution to the interference management problem...... in local areas, basing our study case on LTE-Advanced. We present extensive network simulation results to demonstrate that a simple and robust interference management scheme, called autonomous component carrier selection allows each cell to select the most attractive frequency configuration; improving...... the experience of all users and not just the few best ones; while overall cell capacity is not compromised....

  18. Toward autonomous spacecraft (United States)

    Fogel, L. J.; Calabrese, P. G.; Walsh, M. J.; Owens, A. J.


    Ways in which autonomous behavior of spacecraft can be extended to treat situations wherein a closed loop control by a human may not be appropriate or even possible are explored. Predictive models that minimize mean least squared error and arbitrary cost functions are discussed. A methodology for extracting cyclic components for an arbitrary environment with respect to usual and arbitrary criteria is developed. An approach to prediction and control based on evolutionary programming is outlined. A computer program capable of predicting time series is presented. A design of a control system for a robotic dense with partially unknown physical properties is presented.

  19. Autonomous mobile robot teams (United States)

    Agah, Arvin; Bekey, George A.


    This paper describes autonomous mobile robot teams performing tasks in unstructured environments. The behavior and the intelligence of the group is distributed, and the system does not include a central command base or leader. The novel concept of the Tropism-Based Cognitive Architecture is introduced, which is used by the robots in order to produce behavior transforming their sensory information to proper action. The results of a number of simulation experiments are presented. These experiments include worlds where the robot teams must locate, decompose, and gather objects, and defend themselves against hostile predators, while navigating around stationary and mobile obstacles.

  20. Loss of Roquin induces early death and immune deregulation but not autoimmunity (United States)

    Bertossi, Arianna; Aichinger, Martin; Sansonetti, Paola; Lech, Maciej; Neff, Frauke; Pal, Martin; Wunderlich, F. Thomas; Anders, Hans-Joachim; Klein, Ludger


    The substitution of one amino acid in the Roquin protein by the sanroque mutation induces a dramatic autoimmune syndrome in mice. This is believed to occur through ectopic expression of inducible T cell co-stimulator (ICOS) and unrestrained differentiation of follicular T helper cells, which induce spontaneous germinal center reactions to self-antigens. In this study, we demonstrate that tissue-specific ablation of Roquin in T or B cells, in the entire hematopoietic system, or in epithelial cells of transplanted thymi did not cause autoimmunity. Loss of Roquin induced elevated expression of ICOS through T cell–intrinsic and –extrinsic mechanisms, which itself was not sufficient to break self-tolerance. Instead, ablation of Roquin in the hematopoietic system caused defined changes in immune homeostasis, including the expansion of macrophages, eosinophils, and T cell subsets, most dramatically CD8 effector–like T cells, through cell-autonomous and nonautonomous mechanisms. Germline Roquin deficiency led to perinatal lethality, which was partially rescued on the genetic background of an outbred strain. However, not even complete absence of Roquin resulted in overt self-reactivity, suggesting that the sanroque mutation induces autoimmunity through an as yet unknown mechanism. PMID:21844204

  1. Autoimmunity in diabetics induced by hormonal contaminants of insulin

    International Nuclear Information System (INIS)

    Bloom, S.R.; Barnes, A.J.; Adrian, T.E.; Polak, J.M.


    Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immuno-cytochemical testing showed that antibody-positive diabetic plasmas reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity to naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment. (author)

  2. Autoimmunity in diabetics induced by hormonal contaminants of insulin

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, S R; Barnes, A J; Adrian, T E; Polak, J M [Royal Postgraduate Medical School, London (UK)


    Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immuno-cytochemical testing showed that antibody-positive diabetic plasmas reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity to naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment.

  3. HTLV-1, Immune Response and Autoimmunity

    Directory of Open Access Journals (Sweden)

    Juarez A S Quaresma


    Full Text Available Human T-lymphotropic virus type-1 (HTLV-1 infection is associated with adult T-cell leukemia/lymphoma (ATL. Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA, Systemic Lupus Erythematosus (SLE, and Sjögren’s Syndrome (SS. The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4+ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4+ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity.

  4. The clinical extremes of autoimmune cholangitis

    Directory of Open Access Journals (Sweden)

    Sara Campos

    Full Text Available Autoimmune cholangitis (AIC was first described in 1987 as immunocholangitis in three women who presented with signs and symptoms of primary biliary cholangitis (PBC, but who were antimitochondrial (AMA negative and antinuclear antibodies (ANA positive, and responded to immunosuppressive therapy with azathioprine and prednisolone (1. AIC is a rare chronic cholestatic inflammatory disease characterized by the presence of high ANA or smooth muscle antibodies (SMA but AMA seronegativity. Histologically, AIC exhibits bile duct injury (2. In terms of therapeutics, in addition to response to ursodeoxycholic acid, a prompt response to corticosteroids has also been reported in earlier stages, distinguishing it from PBC. Herein the authors describe two cases with mixed signs of PBC and autoimmune hepatitis (AIH. The diagnostic differentiation between these diseases (AIC, PBC and AIH is essential because of the different therapeutic strategies. Our cases highlight the importance of clinician awareness of the autoimmune spectrum of liver diseases.

  5. Clinical heterogeneity in autoimmune acute liver failure (United States)

    Chavez-Tapia, Norberto C; Martinez-Salgado, Julio; Granados, Julio; Uribe, Misael; Tellez-Avila, Felix I


    AIM: To describe the outcome and prognosis in a cohort of patients with acute liver failure due to autoimmune hepatitis without liver transplantation. METHODS: A retrospective trial was conducted in 11 patients with acute liver failure due to autoimmune hepatitis who attended the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran. Demographic, biochemical and severity indexes, and treatment and outcome were assessed. RESULTS: Among the 11 patients, with a median age of 31 years, 72% had inflammatory response syndrome, and six patients received corticosteroids. The mortality rate within four weeks was 56%, and the one-year survival was 27%. In the survivors, severity indexes were lower and 83% received corticosteroids. CONCLUSION: We observed a relatively high survival rate in patients with acute liver failure due to autoimmune hepatitis. This survival rate could be influenced by severity of the disease and/or use of corticosteroids. PMID:17465474

  6. Pregnancy and autoimmune connective tissue diseases (United States)

    Marder, Wendy; Littlejohn, Emily A


    The autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before and during pregnancy and the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy. PMID:27421217

  7. Autoimmune Hepatitis: A Risk Factor for Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Rajat Garg


    Full Text Available Cholangiocarcinoma (CCA is a very aggressive and lethal tumor, which arises from the epithelial cells of bile ducts. CCA comprises about 3% of all gastrointestinal malignancies and its incidence is on the rise in the recent years. Anatomically, it is classified into intrahepatic, perihilar, or extrahepatic (distal CCA. There are a number of risk factors associated with CCA including primary sclerosing cholangitis, fibropolycystic liver disease, parasitic infection, viral hepatitis, chronic liver disease, and genetic disorders like Lynch syndrome. Autoimmune hepatitis is also recently reported to have an association with development of CCA. We report an interesting case of perihilar CCA in the setting of autoimmune hepatitis along with a literature review. This case highlights the importance of early treatment and close clinical follow-up of patients with autoimmune hepatitis for development of CCA.

  8. Autonomic headache with autonomic seizures: a case report. (United States)

    Ozge, Aynur; Kaleagasi, Hakan; Yalçin Tasmertek, Fazilet


    The aim of the report is to present a case of an autonomic headache associated with autonomic seizures. A 19-year-old male who had had complex partial seizures for 15 years was admitted with autonomic complaints and left hemicranial headache, independent from seizures, that he had had for 2 years and were provoked by watching television. Brain magnetic resonance imaging showed right hippocampal sclerosis and electroencephalography revealed epileptic activity in right hemispheric areas. Treatment with valproic acid decreased the complaints. The headache did not fulfil the criteria for the diagnosis of trigeminal autonomic cephalalgias, and was different from epileptic headache, which was defined as a pressing type pain felt over the forehead for several minutes to a few hours. Although epileptic headache responds to anti-epileptics and the complaints of the present case decreased with antiepileptics, it has been suggested that the headache could be a non-trigeminal autonomic headache instead of an epileptic headache.

  9. Learning for Autonomous Navigation (United States)

    Angelova, Anelia; Howard, Andrew; Matthies, Larry; Tang, Benyang; Turmon, Michael; Mjolsness, Eric


    Robotic ground vehicles for outdoor applications have achieved some remarkable successes, notably in autonomous highway following (Dickmanns, 1987), planetary exploration (1), and off-road navigation on Earth (1). Nevertheless, major challenges remain to enable reliable, high-speed, autonomous navigation in a wide variety of complex, off-road terrain. 3-D perception of terrain geometry with imaging range sensors is the mainstay of off-road driving systems. However, the stopping distance at high speed exceeds the effective lookahead distance of existing range sensors. Prospects for extending the range of 3-D sensors is strongly limited by sensor physics, eye safety of lasers, and related issues. Range sensor limitations also allow vehicles to enter large cul-de-sacs even at low speed, leading to long detours. Moreover, sensing only terrain geometry fails to reveal mechanical properties of terrain that are critical to assessing its traversability, such as potential for slippage, sinkage, and the degree of compliance of potential obstacles. Rovers in the Mars Exploration Rover (MER) mission have got stuck in sand dunes and experienced significant downhill slippage in the vicinity of large rock hazards. Earth-based off-road robots today have very limited ability to discriminate traversable vegetation from non-traversable vegetation or rough ground. It is impossible today to preprogram a system with knowledge of these properties for all types of terrain and weather conditions that might be encountered.

  10. Towards autonomous vehicular clouds

    Directory of Open Access Journals (Sweden)

    Stephan Olariu


    Full Text Available The dawn of the 21st century has seen a growing interest in vehicular networking and its myriad potential applications. The initial view of practitioners and researchers was that radio-equipped vehicles could keep the drivers informed about potential safety risks and increase their awareness of road conditions. The view then expanded to include access to the Internet and associated services. This position paper proposes and promotes a novel and more comprehensive vision namely, that advances in vehicular networks, embedded devices and cloud computing will enable the formation of autonomous clouds of vehicular computing, communication, sensing, power and physical resources. Hence, we coin the term, autonomous vehicular clouds (AVCs. A key feature distinguishing AVCs from conventional cloud computing is that mobile AVC resources can be pooled dynamically to serve authorized users and to enable autonomy in real-time service sharing and management on terrestrial, aerial, or aquatic pathways or theaters of operations. In addition to general-purpose AVCs, we also envision the emergence of specialized AVCs such as mobile analytics laboratories. Furthermore, we envision that the integration of AVCs with ubiquitous smart infrastructures including intelligent transportation systems, smart cities and smart electric power grids will have an enormous societal impact enabling ubiquitous utility cyber-physical services at the right place, right time and with right-sized resources.

  11. Hot topics in autoimmune diseases: perspectives from the 2013 Asian Congress of Autoimmunity. (United States)

    Selmi, Carlo


    Our understanding of the pathogenic mechanisms and possible treatments of autoimmune diseases has significantly increased over the past decade. Nonetheless, numerous major issues remain open and such issues span from epidemiology to clinimetrics and from the role of infectious agents to the search for accurate biomarkers in paradigmatic conditions such as systemic lupus erythematosus, rheumatoid arthritis, and spondyloarthropathies. In the case of cardiovascular comorbidities of autoimmune diseases or, more generally, the pathogenesis of atherosclerosis, fascinating evidence points to a central role of autoimmunity and metabolic dysfunctions and a possible role of therapies targeting inflammation to ameliorate both conditions. Basic science and translational medicine contribute to identify common mechanisms that underlie different autoimmune diseases, as in the case of tumor necrosis factor alpha, and more recently vitamin D, autoantibodies, T and B regulatory cells, and microRNA. Finally, new therapies are expected to significantly change our approach to autoimmune diseases, as represented by the recent FDA approval of the first oral JAK inhibitor. The present article moves from the major topics that were discussed at the 2013 Asian Congress of Autoimmunity in Hong Kong to illustrate the most recent data from leading journals in autoimmunity and immunology. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Autoimmune gastritis: histology phenotype and OLGA staging. (United States)

    Rugge, M; Fassan, M; Pizzi, M; Zorzetto, V; Maddalo, G; Realdon, S; De Bernard, M; Betterle, C; Cappellesso, R; Pennelli, G; de Boni, M; Farinati, F


    Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis. To describe the histological phenotype of autoimmune gastritis, also to test the prognostic impact of OLGA staging in the autoimmune setting. A single-institutional series (spanning the years 2003-2011) of 562 consecutive patients (M:F ratio: 1:3.7; mean age = 57.6 ± 14.4 years) with serologically confirmed autoimmune gastritis underwent histology review and OLGA staging. Helicobacter pylori infection was ascertained histologically in 44/562 cases (7.8%). Forty six biopsy sets (8.2%) featured OLGA stages III-IV; they included all four cases of incidental epithelial neoplasia (three intraepithelial and one invasive; three of these four cases had concomitant H. pylori infection). There were 230 (40.9%) and 139 (24.7%) cases, respectively, of linear and micro-nodular enterochromaffin-like cell hyperplasia; 19 (3.4%) type I carcinoids were detected. The series included 116 patients who underwent repeated endoscopy/biopsy sampling (mean time elapsing between the two procedures = 54 months; range 24-108). Paired histology showed a significant (P = 0.009) trend towards a stage progression [the stage increased in 25/116 cases (22%); it remained unchanged in 87/116 cases (75%)]. In autoimmune gastritis, the cancer risk is restricted to high-risk gastritis stages (III-IV), and is associated mainly with concomitant H. pylori infection. OLGA staging consistently depicts the time-dependent organic progression of the autoimmune disease and provides key information for secondary gastric cancer prevention strategies. © 2012 Blackwell Publishing Ltd.

  13. Human neutrophils in auto-immunity. (United States)

    Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique


    Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. [Autoimmune encephalitis: possibilities in the laboratory investigation]. (United States)

    Böröcz, Katalin; Hayden, Zsófia; Mészáros, Viktória; Csizmadia, Zsuzsanna; Farkas, Kornélia; Kellermayer, Zoltán; Balogh, Péter; Nagy, Ferenc; Berki, Tímea


    The role of autoimmune responses against central nervous system (CNS) antigens in encephalitis presenting with non-classified neurologic or psychiatric symptoms has been appreciated in the past decade. Paraneoplastic limbic encephalitis has a poor prognosis and is most commonly associated with lung, ovarium, and testicular neoplasms, leading to immune reactions against intracellular antigens (anti-Hu/ANNA1, anti-Ri/ANNA2, anti-CV2/CRMP5 and anti-Ma2/Ta). In contrast, the recently described autoimmune encephalitis subtypes present with a broad spectrum of symptoms, respond to autoimmune therapies well and usually associate with autoantibodies against neuronal cell surface receptors (NMDAR, GABA B R, AMPAR) or synaptic proteins (LGI1, CASPR2). Our aim is to bring to awareness the increasing number of autoimmune encephalitis patients requiring neurologic, psychiatric and intensive care and to emphasize the significance of detecting various autoantibodies in diagnosing patients. In the past 6 years, our laboratory received 836 autoimmune encephalitis diagnostic test requests from a total of 717 patients. Serum and cerebrospinal fluid (CSF) samples were analysed with indirect immunofluorescence using a BIOCHIP consisting of cell lines transfected with 6 different receptor proteins. IgG autoantibodies against receptor proteins were present in 7.5% of patients. The frequency of positive samples was the following: NMDAR > LGI1 > GABA B R > CASPR2. Detecting autoantibodies facilitates the diagnosis of autoimmune encephalitis in an early stage. Patients diagnosed early can be effectively treated with plasmapheresis and immunosuppressive drugs. The efficiency of therapies can be monitored by autoantibody detection. Therefore, the diagnostic immune laboratory plays an important role in proper diagnosis and in the prevention of rapidly progressing symptoms. Orv Hetil. 2018; 159(3): 107-112.

  15. Diagnosis and Management of Pediatric Autoimmune Liver Disease : ESPGHAN Hepatology Committee Position Statement

    NARCIS (Netherlands)

    Mieli-Vergani, Giorgina; Vergani, Diego; Baumann, Ulrich; Czubkowski, Piotr; Debray, Dominique; Dezsofi, Antal; Fischler, Björn; Gupte, Girish; Hierro, Loreto; Indolfi, Giuseppe; Jahnel, Jörg; Smets, Françoise; Verkade, Henkjan J; Hadžić, Nedim

    Paediatric autoimmune liver disease is characterised by inflammatory liver histology, circulating autoantibodies and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis

  16. Gender and autoimmune comorbidity in multiple sclerosis

    DEFF Research Database (Denmark)

    Magyari, Melinda; Koch-Henriksen, Nils; Pfleger, Claudia C


    BACKGROUND: The female preponderance in incidence of multiple sclerosis (MS) calls for investigations into sex differences in comorbidity with other autoimmune diseases (ADs). OBJECTIVES: To determine whether male and female patients with MS have a higher frequency of autoimmune comorbidity than...... controls, and to describe the type and frequency of ADs that are associated with MS. METHODS: Our database was established by linkage of the Danish MS Registry to The Danish National Patient Register and consisted of 1403 patients of both sexes with clinical onset of MS between 2000 and 2004, and 25...

  17. Behavioural domain knowledge transfer for autonomous agents

    CSIR Research Space (South Africa)

    Rosman, Benjamin S


    Full Text Available , and Behavior Transfer in Autonomous Robots, AAAI 2014 Fall Symposium Series, 13-15 November 2014 Behavioural Domain Knowledge Transfer for Autonomous Agents Benjamin Rosman Mobile Intelligent Autonomous Systems Modelling and Digital Science Council...

  18. From cooperative to autonomous vehicles

    NARCIS (Netherlands)

    van der Sande, T.P.J.; Nijmeijer, H.; Fossen, T.I.; Pettersen, K.Y.; Nijmeijer, H.


    What defines an autonomous vehicle? In this chapter the authors will try to answer this question and formulate the limitations of driver assistance systems as well as for—conditionally—autonomous vehicles . First a short summary of the levels of automation as provided by the society of automotive

  19. Autonomous Learner Model Resource Book (United States)

    Betts, George T.; Carey, Robin J.; Kapushion, Blanche M.


    "Autonomous Learner Model Resource Book" includes activities and strategies to support the development of autonomous learners. More than 40 activities are included, all geared to the emotional, social, cognitive, and physical development of students. Teachers may use these activities and strategies with the entire class, small groups, or…

  20. Generalized Vitiligo Associated Autoimmune Diseases in Japanese Patients Their Families

    Directory of Open Access Journals (Sweden)

    Tomohiko Narita


    Conclusions: Among Japanese vitiligo patients, there is a subgroup with strong evidence of genetically determined susceptibility to not only vitiligo, but also to autoimmune thyroid disease and other autoimmune disorders.

  1. Cancer immunotherapy in patients with preexisting autoimmune disorders

    DEFF Research Database (Denmark)

    Donia, Marco; Pedersen, Magnus; Svane, Inge Marie


    Patients with preexisting active autoimmune disorders were excluded from clinical trials of immune checkpoint inhibitors. However, patients with autoimmune disorders are diagnosed with cancer at least as frequently as the global population, and clinicians treating patients outside clinical trials...

  2. Genetics Home Reference: autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (United States)

    ... Facebook Twitter Home Health Conditions APECED Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Printable PDF Open All Close All ... view the expand/collapse boxes. Description Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy ( APECED ) is an inherited condition that ...

  3. Ten Putative Contributors to the Obesity Epidemic (United States)

    McAllister, Emily J.; Dhurandhar, Nikhil V.; Keith, Scott W.; Aronne, Louis J.; Barger, Jamie; Baskin, Monica; Benca, Ruth M.; Biggio, Joseph; Boggiano, Mary M.; Eisenmann, Joe C.; Elobeid, Mai; Fontaine, Kevin R.; Gluckman, Peter; Hanlon, Erin C.; Katzmarzyk, Peter; Pietrobelli, Angelo; Redden, David T.; Ruden, Douglas M.; Wang, Chenxi; Waterland, Robert A.; Wright, Suzanne M.; Allison, David B.


    The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects, as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic. PMID:19960394

  4. Role of the X-linked gene GPR174 in autoimmune Addison's disease. (United States)

    Napier, C; Mitchell, A L; Gan, E; Wilson, I; Pearce, S H S


    Autoimmune endocrinopathies demonstrate a profound gender bias, but the reasons for this remain obscure. The 1000 genes on the X chromosome are likely to be implicated in this inherent susceptibility; various theories, including skewed X chromosome inactivation and fetal microchimerism, have been proposed. GPR174 is an Xq21 putative purinergic receptor that is widely expressed in lymphoid tissues. A single-nucleotide polymorphism, rs3827440, encoding Ser162Pro, has recently been associated with Graves' disease in Chinese and Polish populations, suggesting a role of this X chromosome gene in autoimmune disease. We investigated the role of rs3827440 in a UK cohort of patients with autoimmune Addison's disease (AAD). Samples from 286 AAD cases and 288 healthy controls were genotyped using TaqMan single-nucleotide polymorphism genotyping assays (C_25954273_10) on the Applied Biosystems 7900HT Fast real-time PCR system. Using a dominant (present/absent) model, the serine-encoding T allele of rs3827440 was present in 189 of 286 AAD patients (66%) compared with 132 of 288 unaffected controls (46%) [P = .010, odds ratio 1.80 (5%-95% confidence interval 1.22-2.67)]. An allele dosage model found a significant excess of the T allele in AAD patients compared with controls [P = .03, odds ratio 1.34 (5%-95% confidence interval 1.07-1.67)]. We have demonstrated a significant association of this X chromosome-encoded immunoreceptor with AAD for the first time. This X-linked gene could have a more generalized role in autoimmunity pathogenesis: G protein-coupled receptors are promising drugable targets, and further work to elucidate the functional role of GPR174 is now warranted.

  5. Shared genetic origins of allergy and autoimmune diseases

    DEFF Research Database (Denmark)

    Waage, J. E.; Kreiner-Møller, E.; Standl, M.


    Parallel increases in allergy and autoimmune disease prevalence in recent time suggest shared, but yet unknown, etiologies. Here, we investigated shared genetic loci and molecular pathways to identify possible shared disease mechanisms between allergy and autoimmune diseases.......Parallel increases in allergy and autoimmune disease prevalence in recent time suggest shared, but yet unknown, etiologies. Here, we investigated shared genetic loci and molecular pathways to identify possible shared disease mechanisms between allergy and autoimmune diseases....

  6. Research Institute for Autonomous Precision Guided Systems

    National Research Council Canada - National Science Library

    Rogacki, John R


    ... vehicles, cooperative flight of autonomous aerial vehicles using GPS and vision information, cooperative and sharing of information in search missions involving multiple autonomous agents, multi-scale...

  7. Mobile Autonomous Reconfigurable System

    Directory of Open Access Journals (Sweden)

    Pavliuk N.A.


    Full Text Available The object of this study is a multifunctional modular robot able to assemble independently in a given configuration and responsively change it in the process of operation depending on the current task. In this work we aim at developing and examining unified modules for a modular robot, which can both perform autonomous movement and form a complex structure by connecting to other modules. The existing solutions in the field of modular robotics were reviewed and classified by power supply, the ways of interconnection, the ways of movement and the possibility of independent movement of separate modules. Basing on the analysis of the shortcomings of existing analogues, we have developed a module of mobile autonomous reconfigurable system, including a base unit, a set of magneto-mechanical connectors and two motor wheels. The basic kinematic scheme of the modular robot, the features of a single module, as well as the modular structure formed by an array of similar modules were described. Two schemes for placing sets of magneto-mechanical connectors in the basic module have been proposed. We described the principle of operation of a magneto-mechanical connector based on redirection of the magnetic flux of a permanent magnet. This solution simplifies the system for controlling a mechanism of connection with other modules, increases energy efficiency and a battery life of the module. Since the energy is required only at the moment of switching the operating modes of the connector, there is no need to power constantly the connector mechanism to maintain the coupling mode.

  8. The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity. (United States)

    Segal, Yahel; Dahan, Shani; Sharif, Kassem; Bragazzi, Nicola Luigi; Watad, Abdulla; Amital, Howard


    Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Autoimmune hepatitis : Pathogenesis, diagnosis and treatment

    NARCIS (Netherlands)

    van den Berg, AP

    Background: Autoimmune hepatitis (AIH) is a chronic necro-inflammatory disease of the liver. Early recognition is important in order to prevent the development of cirrosis. This review discusses recent developments in the fields of diagnosis, pathophysiology and management of AIH. Methods: Relevant

  10. Capillaroscopy in diagnostic of systemic autoimmune diseases

    International Nuclear Information System (INIS)

    Garra, V.; Danese, N.; Rebella, M.


    The diagnosis of systemic autoimmune diseases is carried out by combining clinical, paraclinical, imaging and anatomopathological data. However, in many cases is necessary to access other guiding parameters. The capillaroscopy is a technique that consists in the observation of capillary microcirculation in the proximal nail fold hands. The methods used are the videocapillaroscopy (microscopy, stereoscopic)

  11. Premature atherosclerosis in systemic autoimmune diseases

    NARCIS (Netherlands)

    Leeuw, Karina de


    Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and Wegener’s granulomatosis (WG) are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared to age- and sex-matched controls. Many risk factors are involved in the pathogenesis of

  12. Celiac disease in autoimmune cholestatic liver disorders. (United States)

    Volta, Umberto; Rodrigo, Luis; Granito, Alessandro; Petrolini, Nunzio; Muratori, Paolo; Muratori, Luigi; Linares, Antonio; Veronesi, Lorenza; Fuentes, Dolores; Zauli, Daniela; Bianchi, Francesco B


    In this study, serological screening for celiac disease (CD) was performed in patients with autoimmune cholestasis to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy. Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255 patients with primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis. Immunoglobulin A endomysial and human tissue transglutaminase antibodies were positive in nine patients (seven primary biliary cirrhosis, one autoimmune cholangitis, and one primary sclerosing cholangitis), whose duodenal biopsy results showed villous atrophy consistent with CD. Two of these patients had a malabsorption syndrome, and one had iron-deficiency anemia. Clinical and biochemical signs of cholestasis did not improve after gluten withdrawal in the three patients with severe liver disease. A longer follow-up of the six celiac patients with mild liver damage is needed to clarify whether gluten restriction can contribute to slow down the progression of liver disease. The high prevalence of CD (3.5%) in autoimmune cholestasis suggests that serological screening for CD should be routinely performed in such patients by immunoglobulin A endomysial or human tissue transglutaminase antibodies.

  13. Autoimmun hepatitis. Fremtroedelsesformer, diagnostik og behandling

    DEFF Research Database (Denmark)

    Poulsen, L O; Tage-Jensen, U; Vyberg, M


    A retrospective study concerning ten patients with autoimmune hepatitis (AiH), diagnosed during a 2 1/2-year period is presented. The age of the patients ranged from 25 to 82 years and nine of the patients were women. Their symptoms included jaundice, pruritus, fever, anorexia and fatigue during...

  14. Study of cytokines microenvironment during autoimmune diseases ...

    African Journals Online (AJOL)

    22, IL-23, TNF-α and TGF-β) were determined. We used the immunoenzymatic technology to assess the titer of cytokines. We found that there was no significant variation of TNF-α level in normal controls and autoimmune diseases ...

  15. The environment and autoimmune thyroid diseases

    NARCIS (Netherlands)

    Prummel, Mark F.; Strieder, Thea; Wiersinga, Wilmar M.


    Genetic factors play an important role in the pathogenesis of autoimmune thyroid disease (AITD) and it has been calculated that 80% of the susceptibility to develop Graves' disease is attributable to genes. The concordance rate for AITD among monozygotic twins is, however, well below I and

  16. Is Tourette's syndrome an autoimmune disease?

    NARCIS (Netherlands)

    Hoekstra, PJ; Kallenberg, CGM; Korf, J; Minderaa, RB


    We provide a review of recent research findings which support the involvement of autoimmunity in childhood-onset tic disorders, in particular the presence of antineuronal autoantibodies, D8/17 B lymphocyte overexpression, a marker of chorea associated with streptococcal infection, and possible

  17. Gene expression profiling in autoimmune diseases

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo


    A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA...

  18. Autoimmune hepatitis in children in Eastern Denmark

    DEFF Research Database (Denmark)

    Vitfell-Pedersen, Joanna; Jørgensen, Marianne Hørby; Müller, Klaus


    Autoimmune hepatitis (AIH) in childhood is a progressive chronic inflammatory liver disease. The aim of this study was to compare the clinical and biochemical characteristics of 33 paediatric patients diagnosed as having AIH with earlier described cohorts, and to examine the effect of early...

  19. Auto-immune Haemolytic Anaemia and Paroxys

    African Journals Online (AJOL)

    who presented with an acute auto-immune haemolytic anaemia. In addition to a persistently positive Coombs test, with specific red cell auto-antibodies, the acidified serum test and the sucrose haemolysis test were repeatedly positive. CASE REPORT. A 24-year-old Indian woman was admitted to hospital in. July 1969.

  20. Autoimmun hypophysitis--en differentialdiagnose til hypofyseadenomer

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus


    A 66-year-old man with a headache in the left temporal region which had persisted for eight months is presented. The patient developed polydipsia and polyuria and also suffered from tinnitus, impaired hearing and episodes of double vision. The patient was diagnosed with autoimmune hypophysitis (AH...

  1. Is Tourette's syndrome an autoimmune disease?

    NARCIS (Netherlands)

    Hoekstra, P; Limburg, P; Kallenberg, C; Minderaa, R; Battistin, L


    Tourette's syndrome is a childhood-onset neuropsychiatric disorder characterized by the presence of both multiple motor and vocal tics. While its pathogenesis at a molecular and cellular level remains unknown, recent research findings point to the possible involvement of autoimmunity in at least a

  2. Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis (United States)

    Grayson, Peter C.; Sloan, J. Mark; Niles, John L.; Monach, Paul A.; Merkel, Peter A.


    Objectives Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 – October 2010. A PubMed database search of the medical literature was performed for papers published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results A 49 year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsy-proven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a post-recovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV. PMID:21507463

  3. Eating Disorders, Autoimmune, and Autoinflammatory Disease. (United States)

    Zerwas, Stephanie; Larsen, Janne Tidselbak; Petersen, Liselotte; Thornton, Laura M; Quaranta, Michela; Koch, Susanne Vinkel; Pisetsky, David; Mortensen, Preben Bo; Bulik, Cynthia M


    Identifying factors associated with risk for eating disorders is important for clarifying etiology and for enhancing early detection of eating disorders in primary care. We hypothesized that autoimmune and autoinflammatory diseases would be associated with eating disorders in children and adolescents and that family history of these illnesses would be associated with eating disorders in probands. In this large, nationwide, population-based cohort study of all children and adolescents born in Denmark between 1989 and 2006 and managed until 2012, Danish medical registers captured all inpatient and outpatient diagnoses of eating disorders and autoimmune and autoinflammatory diseases. The study population included 930 977 individuals (48.7% girls). Cox proportional hazards regression models and logistic regression were applied to evaluate associations. We found significantly higher hazards of eating disorders for children and adolescents with autoimmune or autoinflammatory diseases: 36% higher hazard for anorexia nervosa, 73% for bulimia nervosa, and 72% for an eating disorder not otherwise specified. The association was particularly strong in boys. Parental autoimmune or autoinflammatory disease history was associated with significantly increased odds for anorexia nervosa (odds ratio [OR] = 1.13, confidence interval [CI] = 1.01-1.25), bulimia nervosa (OR = 1.29; CI = 1.08-1.55) and for an eating disorder not otherwise specified (OR = 1.27; CI = 1.13-1.44). Autoimmune and autoinflammatory diseases are associated with increased risk for eating disorders. Ultimately, understanding the role of immune system disturbance for the etiology and pathogenesis of eating disorders could point toward novel treatment targets. Copyright © 2017 by the American Academy of Pediatrics.

  4. Genomics and proteomics: Applications in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Wolfgang Hueber


    Full Text Available Wolfgang Hueber1,2,3, William H Robinson1,21VA Palo Alto Health Care System, Palo Alto, CA, USA; 2Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; 3Novartis Institutes of Biomedical Research, Novartis, Basle, SwitzerlandAbstract: Tremendous progress has been made over the past decade in the development and refinement of genomic and proteomic technologies for the identification of novel drug targets and molecular signatures associated with clinically important disease states, disease subsets, or differential responses to therapies. The rapid progress in high-throughput technologies has been preceded and paralleled by the elucidation of cytokine networks, followed by the stepwise clinical development of pathway-specific biological therapies that revolutionized the treatment of autoimmune diseases. Together, these advances provide opportunities for a long-anticipated personalized medicine approach to the treatment of autoimmune disease. The ever-increasing numbers of novel, innovative therapies will need to be harnessed wisely to achieve optimal long-term outcomes in as many patients as possible while complying with the demands of health authorities and health care providers for evidence-based, economically sound prescription of these expensive drugs. Genomic and proteomic profiling of patients with autoimmune diseases holds great promise in two major clinical areas: (1 rapid identification of new targets for the development of innovative therapies and (2 identification of patients who will experience optimal benefit and minimal risk from a specific (targeted therapy. In this review, we attempt to capture important recent developments in the application of genomic and proteomic technologies to translational research by discussing informative examples covering a diversity of autoimmune diseases.Keywords: proteomics, genomics, autoimmune diseases, antigen microarrays, 2-Dih, rheumatoid arthritis

  5. Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases. (United States)

    Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M


    Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

  6. Psoriasis, Psoriatic Arthritis, and Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Ilaria Ruffilli


    Full Text Available Psoriasis (PsO is a chronic relapsing/remitting autoimmune skin disease, associated with an increased risk of other autoimmune disorders. Psoriatic arthritis (PsA is a chronic inflammatory arthritis occurring approximately in 30% of PsO patients. Sporadic cases of association between PsO and autoimmune thyroid disorders (AITDs have been reported. However, two different recent studies did not find any association between them. In patients with PsO and PsA, an association with AITD has been shown by most of the studies in adults, but not in the juvenile form. In PsA women and men, thyroid autoimmunity [positive antithyroid peroxidase (AbTPO antibodies, hypoechoic thyroid pattern] and subclinical hypothyroidism were more prevalent than in the general population. An association has been shown also in patients with PsO, arthritis, and inflammatory bowel disease, who have more frequently AITD. A Th1 immune predominance has been shown in early PsO, and PsA, with high serum CXCL10 (Th1 prototype chemokine, overall in the presence of autoimmune thyroiditis. This Th1 immune predominance might be the immunopathogenetic base of the association of these disorders. A raised incidence of new cases of hypothyroidism, thyroid dysfunction, positive AbTPO, and appearance of a hypoechoic thyroid pattern in PsA patients, especially in women, has been shown recently, suggesting to evaluate AbTPO levels, thyroid function, and thyroid ultrasound, especially in PsA women. Thyroid function follow-up and suitable treatments should be performed regularly in PsA female patients at high risk (thyroid-stimulating hormone within the normal range but at the higher limit, positive AbTPO, hypoechoic, and small thyroid.

  7. Clinical significance of autoantibodies in autoimmune hepatitis. (United States)

    Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego


    The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Impact of Autoantibodies against Glycolytic Enzymes on Pathogenicity of Autoimmune Retinopathy and Other Autoimmune Disorders

    Directory of Open Access Journals (Sweden)

    Grazyna Adamus


    Full Text Available Autoantibodies (AAbs against glycolytic enzymes: aldolase, α-enolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in sera of patients with blinding retinal diseases, such as paraneoplastic [cancer-associated retinopathy (CAR] and non-paraneoplastic autoimmune retinopathies, as well as in many other autoimmune diseases. CAR is a degenerative disease of the retina characterized by sudden vision loss in patients with cancer and serum anti-retinal AAbs. In this review, we discuss the widespread serum presence of anti-glycolytic enzyme AAbs and their significance in autoimmune diseases. There are multiple mechanisms responsible for antibody generation, including the innate anti-microbial response, anti-tumor response, or autoimmune response against released self-antigens from damaged, inflamed tissue. AAbs against enolase, GADPH, and aldolase exist in a single patient in elevated titers, suggesting their participation in pathogenicity. The lack of restriction of AAbs to one disease may be related to an increased expression of glycolytic enzymes in various metabolically active tissues that triggers an autoimmune response and generation of AAbs with the same specificity in several chronic and autoimmune conditions. In CAR, the importance of serum anti-glycolytic enzyme AAbs had been previously dismissed, but the retina may be without pathological consequence until a failure of the blood–retinal barrier function, which would then allow pathogenic AAbs access to their retinal targets, ultimately leading to damaging effects.

  9. Putative neuroprotective agents in neuropsychiatric disorders. (United States)

    Dodd, Seetal; Maes, Michael; Anderson, George; Dean, Olivia M; Moylan, Steven; Berk, Michael


    In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Seronegative and seropositive autoimmune autonomic ganglionopathy (AAG): Same clinical picture, same response to immunotherapy. (United States)

    Tijero, Beatriz; Del Pino, Rocio; Pérez-Concha, Tomás; Acera, Maria Angeles; Gabilondo, Iñigo; Berganzo, Koldo; Graus, Frances; Martinez-Alday, Jesus Daniel; Barcena, Joseba; Gómez-Esteban, Juan Carlos


    Two patients with a syndrome of pandisautonomia with clinical criteria of AAG are provided. Both patients present a similar clinical picture and response to immunosuppressive treatment. One of them has positive antibodies against the ganglionic nicotinic acetylcholine (gAChr) and the other does not. This brief article serves to reflect the spectrum of AAG, at a clinical level, in laboratory tests and in the response to immunotherapy, independently of the presence of positive gAChr antibodies. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Cybersecurity for aerospace autonomous systems (United States)

    Straub, Jeremy


    High profile breaches have occurred across numerous information systems. One area where attacks are particularly problematic is autonomous control systems. This paper considers the aerospace information system, focusing on elements that interact with autonomous control systems (e.g., onboard UAVs). It discusses the trust placed in the autonomous systems and supporting systems (e.g., navigational aids) and how this trust can be validated. Approaches to remotely detect the UAV compromise, without relying on the onboard software (on a potentially compromised system) as part of the process are discussed. How different levels of autonomy (task-based, goal-based, mission-based) impact this remote characterization is considered.

  12. Decentralized Control of Autonomous Vehicles (United States)


    Autonomous Vehicles by John S. Baras, Xiaobo Tan, Pedram Hovareshti CSHCN TR 2003-8 (ISR TR 2003-14) Report Documentation Page Form ApprovedOMB No. 0704...AND SUBTITLE Decentralized Control of Autonomous Vehicles 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Decentralized Control of Autonomous Vehicles ∗ John S. Baras, Xiaobo Tan, and Pedram

  13. Infections as risk factor for autoimmune diseases - A nationwide study

    DEFF Research Database (Denmark)

    Nielsen, Philip Rising; Kragstrup, Tue Wenzel; Deleuran, Bent Winding


    Viruses, bacteria and other infectious pathogens are the major postulated environmental triggers of autoimmunity. In the present nation-wide study we describe the association between infections and 29 autoimmune diseases. We used the Danish Civil Registration System to identify 4.5 million persons...... to the etiology of autoimmune diseases together with genetic factors....... born between 1945 and 2000. Information on infections and autoimmune diseases was obtained from the Danish Hospital Register. The cohort was followed from 1977 to 2012. Incidence rate ratios for developing an autoimmune disease were estimated using poisson regression. We found an association between...

  14. Helicobacter pylori and autoimmune disease: Cause or bystander (United States)

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P


    Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

  15. Therapeutic Potential of Invariant Natural Killer T Cells in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Luc Van Kaer


    Full Text Available Tolerance against self-antigens is regulated by a variety of cell types with immunoregulatory properties, such as CD1d-restricted invariant natural killer T (iNKT cells. In many experimental models of autoimmunity, iNKT cells promote self-tolerance and protect against autoimmunity. These findings are supported by studies with patients suffering from autoimmune diseases. Based on these studies, the therapeutic potential of iNKT cells in autoimmunity has been explored. Many of these studies have been performed with the potent iNKT cell agonist KRN7000 or its structural variants. These findings have generated promising results in several autoimmune diseases, although mechanisms by which iNKT cells modulate autoimmunity remain incompletely understood. Here, we will review these preclinical studies and discuss the prospects for translating their findings to patients suffering from autoimmune diseases.

  16. [Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus]. (United States)

    Krysiak, Robert; Okopień, Bogusław


    Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

  17. The Autonomous Student: A Footnote. (United States)

    Long, Jancis


    An argument that rationality is a learned behavior, rather than a natural facility, is developed vis-a-vis certain educational theories. The difficulties students face in maintaining a rational stance in an autonomous classroom are also discussed. (JL)

  18. Structural Discrimination and Autonomous Vehicles

    DEFF Research Database (Denmark)

    Liu, Hin-Yan


    This paper examines the potential for structural discrimination to be woven into the fabric of autonomous vehicle developments, which remain underexplored and undiscussed. The prospect for structural discrimination arises as a result of the coordinated modes of autonomous vehicle behaviour...... individual identity, and potentially relative worth, to autonomous vehicles engaging in a crash damage calculus. At the risk of introducing these ideas into the development of autonomous vehicles, this paper hopes to spark a debate to foreclose these eventualities....... that is prescribed by its code. This leads to the potential for individuated outcomes to be networked and thereby multiplied consistently to any number of vehicles implementing such a code. The aggregated effects of such algorithmic policy preferences will thus cumulate in the reallocation of benefits and burdens...

  19. Simple autonomous Mars walker (United States)

    Larimer, Stanley J.; Lisec, Thomas R.; Spiessbach, Andrew J.


    Under a contract with NASA's Jet Propulsion Laboratory, Martin Marietta has developed several alternative rover concepts for unmanned exploration of the planet Mars. One of those concepts, the 'Walking Beam', is the subject of this paper. This concept was developed with the goal of achieving many of the capabilities of more sophisticated articulated-leg walkers with a much simpler, more robust, less computationally demanding and more power efficient design. It consists of two large-base tripods nested one within the other which alternately translate with respect to each other along a 5-meter beam to propel the vehicle. The semiautonomous navigation system relies on terrain geometry sensors and tacticle feedback from each foot to autonomously select a path which avoids hazards along a route designated from earth. Both mobility and navigation features of this concept are discussed including a top-level description of the vehicle's physical characteristics, deployment strategy, mobility elements, sensor suite, theory of operation, navigation and control processes, and estimated performance.

  20. Is paramecium swimming autonomic? (United States)

    Bandyopadhyay, Promode R.; Toplosky, Norman; Hansen, Joshua


    We seek to explore if the swimming of paramecium has an underlying autonomic mechanism. Such robotic elements may be useful in capturing the disturbance field in an environment in real time. Experimental evidence is emerging that motion control neurons of other animals may be present in paramecium as well. The limit cycle determined using analog simulation of the coupled nonlinear oscillators of olivo-cerebellar dynamics (ieee joe 33, 563-578, 2008) agrees with the tracks of the cilium of a biological paramecium. A 4-motor apparatus has been built that reproduces the kinematics of the cilium motion. The motion of the biological cilium has been analyzed and compared with the results of the finite element modeling of forces on a cilium. The modeling equates applied torque at the base of the cilium with drag, the cilium stiffness being phase dependent. A low friction pendulum apparatus with a multiplicity of electromagnetic actuators is being built for verifying the maps of the attractor basin computed using the olivo-cerebellar dynamics for different initial conditions. Sponsored by ONR 33.

  1. Autonomous Energy Grids: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Kroposki, Benjamin D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Dall-Anese, Emiliano [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Bernstein, Andrey [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Zhang, Yingchen [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hodge, Brian S [National Renewable Energy Laboratory (NREL), Golden, CO (United States)


    With much higher levels of distributed energy resources - variable generation, energy storage, and controllable loads just to mention a few - being deployed into power systems, the data deluge from pervasive metering of energy grids, and the shaping of multi-level ancillary-service markets, current frameworks to monitoring, controlling, and optimizing large-scale energy systems are becoming increasingly inadequate. This position paper outlines the concept of 'Autonomous Energy Grids' (AEGs) - systems that are supported by a scalable, reconfigurable, and self-organizing information and control infrastructure, can be extremely secure and resilient (self-healing), and self-optimize themselves in real-time for economic and reliable performance while systematically integrating energy in all forms. AEGs rely on scalable, self-configuring cellular building blocks that ensure that each 'cell' can self-optimize when isolated from a larger grid as well as partaking in the optimal operation of a larger grid when interconnected. To realize this vision, this paper describes the concepts and key research directions in the broad domains of optimization theory, control theory, big-data analytics, and complex system modeling that will be necessary to realize the AEG vision.


    Energy Technology Data Exchange (ETDEWEB)

    Lindner, Robert R.; Vera-Ciro, Carlos; Murray, Claire E.; Stanimirović, Snežana; Babler, Brian [Department of Astronomy, University of Wisconsin, 475 North Charter Street, Madison, WI 53706 (United States); Heiles, Carl [Radio Astronomy Lab, UC Berkeley, 601 Campbell Hall, Berkeley, CA 94720 (United States); Hennebelle, Patrick [Laboratoire AIM, Paris-Saclay, CEA/IRFU/SAp-CNRS-Université Paris Diderot, F-91191 Gif-sur Yvette Cedex (France); Goss, W. M. [National Radio Astronomy Observatory, P.O. Box O, 1003 Lopezville, Socorro, NM 87801 (United States); Dickey, John, E-mail: [University of Tasmania, School of Maths and Physics, Private Bag 37, Hobart, TAS 7001 (Australia)


    We present a new algorithm, named Autonomous Gaussian Decomposition (AGD), for automatically decomposing spectra into Gaussian components. AGD uses derivative spectroscopy and machine learning to provide optimized guesses for the number of Gaussian components in the data, and also their locations, widths, and amplitudes. We test AGD and find that it produces results comparable to human-derived solutions on 21 cm absorption spectra from the 21 cm SPectral line Observations of Neutral Gas with the EVLA (21-SPONGE) survey. We use AGD with Monte Carlo methods to derive the H i line completeness as a function of peak optical depth and velocity width for the 21-SPONGE data, and also show that the results of AGD are stable against varying observational noise intensity. The autonomy and computational efficiency of the method over traditional manual Gaussian fits allow for truly unbiased comparisons between observations and simulations, and for the ability to scale up and interpret the very large data volumes from the upcoming Square Kilometer Array and pathfinder telescopes.


    International Nuclear Information System (INIS)

    Lindner, Robert R.; Vera-Ciro, Carlos; Murray, Claire E.; Stanimirović, Snežana; Babler, Brian; Heiles, Carl; Hennebelle, Patrick; Goss, W. M.; Dickey, John


    We present a new algorithm, named Autonomous Gaussian Decomposition (AGD), for automatically decomposing spectra into Gaussian components. AGD uses derivative spectroscopy and machine learning to provide optimized guesses for the number of Gaussian components in the data, and also their locations, widths, and amplitudes. We test AGD and find that it produces results comparable to human-derived solutions on 21 cm absorption spectra from the 21 cm SPectral line Observations of Neutral Gas with the EVLA (21-SPONGE) survey. We use AGD with Monte Carlo methods to derive the H i line completeness as a function of peak optical depth and velocity width for the 21-SPONGE data, and also show that the results of AGD are stable against varying observational noise intensity. The autonomy and computational efficiency of the method over traditional manual Gaussian fits allow for truly unbiased comparisons between observations and simulations, and for the ability to scale up and interpret the very large data volumes from the upcoming Square Kilometer Array and pathfinder telescopes

  4. Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells. (United States)

    De Bellis, A; Sinisi, A A; Pane, E; Dello Iacovo, A; Bellastella, G; Di Scala, G; Falorni, A; Giavoli, C; Gasco, V; Giordano, R; Ambrosio, M R; Colao, A; Bizzarro, A; Bellastella, A


    Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. We conducted a cross-sectional cohort study. Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

  5. Design of Autonomous Gel Actuators

    Directory of Open Access Journals (Sweden)

    Shuji Hashimoto


    Full Text Available In this paper, we introduce autonomous gel actuators driven by chemical energy. The polymer gels prepared here have cyclic chemical reaction networks. With a cyclic reaction, the polymer gels generate periodical motion. The periodic motion of the gel is produced by the chemical energy of the oscillatory Belouzov-Zhabotinsky (BZ reaction. We have succeeded in making synthetic polymer gel move autonomously like a living organism. This experimental fact represents the great possibility of the chemical robot.

  6. Analysis of Hydraulic Flood Control Structure at Putat Boro River


    Ruzziyatno, Ruhban


    Putat Boro River is one of the main drainage systems of Surakarta city which drains into Bengawan Solo river. The primary problem when flood occur is the higher water level of Bengawan Solo than Boro River and then backwater occur and inundates Putat Boro River. The objective of the study is to obtain operational method of Putat Boro River floodgate to control both inflows and outflows not only during flood but also normal condition. It also aims to know the Putat Boro rivers floodgate op...

  7. Increased prevalence of autoimmunity in Turner syndrome

    DEFF Research Database (Denmark)

    Mortensen, K H; Cleemann, L; Hjerrild, B E


    and karyotype. In conclusion, TS girls and women face a high prevalence of autoimmunity and associated disease with a preponderance towards hypothyroidism and CD. Thus, health care providers dealing with this patient group should be observant and test liberally for these conditions even before clinical symptoms......Individuals with Turner syndrome (TS) are prone to develop autoimmune conditions such as coeliac disease (CD), thyroiditis and type 1 diabetes (T1DM). The objective of the present study was to examine TS of various karyotypes for autoantibodies and corresponding diseases. This was investigated...... hypothyroid. Overall, 18% (19) presented with CD autoantibodies, of whom 26% (five) had CD. Anti-TPO and CD autoantibodies co-existed in 9% (10). Immunoglobulin A deficiency was found in 3% (three) of patients, who all had CD autoantibodies without disease. Among four patients with anti-GAD-65 none had T1DM...

  8. Fetal microchimeric cells in autoimmune thyroid diseases (United States)

    Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter


    Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD. PMID:23723083

  9. Neuroelectrophysiological studies on neurological autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Yin-hong LIU


    Full Text Available The neuroelectrophysiological manifestations of four clinical typical neurological autoimmune diseases including multiple sclerosis (MS, Guillain-Barré syndrome (GBS, myasthenia gravis (MG, and polymyositis and dermatomyositis were reviewed in this paper. The diagnostic value of evoked potentials for multiple sclerosis, nerve conduction studies (NCS for Guillain-Barré syndrome, repetitive nerve stimulation (RNS and single-fiber electromyography (SFEMG for myasthenia gravis, and needle electromyography for polymyositis and dermatomyositis were respectively discussed. This review will help to have comprehensive understanding on electrophysiological examinations and their clinical significance in the diagnosis of neurological autoimmune diseases. doi: 10.3969/j.issn.1672-6731.2014.09.004

  10. The toxic autoimmune syndrome with pulmonary edema

    International Nuclear Information System (INIS)

    Parizhskij, Z.M.; Artyunina, G.P.; Trofimova, T.N.


    A case was considered in detail of a patient with pulmonary edema of immunnocomplex nature in aerogenic intoxication by nickel tetracarbonyl. It was shown that acute aerogenic intoxication nickel carbonyl by led to unfolded toxic autoimmune syndrome. In this case autoimmune immunecomplex pulmonary lesion (AIPL) menifested by progressing pulmonary edema with expressed parenchymatous respiratory insufficiency played a leading role. Lesion of endothelium of pulmonary capillaries by immune complexes has the most significant in pathogenesis of pulmonary edema. The fact that edema appears due to AIPL, is confirmed by high efficiency of glucocorticoid therapy. Use of glucorticoids serves as a diagnostic test which provides an effective roentgenologic diagnosis of AIPL and differential diagnosis of any other pathological processes in the lungs

  11. Haralampos M. Moutsopoulos: a lifetime in autoimmunity. (United States)

    Youinou, Pierre


    Three years ago, the Journal of Autoimmunity and Autoimmunity Reviews launched a series of special issues devoted to the contributions of outstanding scholars in autoimmunology. The special issues are devoted not only to recognize achievements, but also to include a series of dedicated papers that reflect the scholar's work, but also are cutting-edge research and reviews in immunology. This special issue is devoted to Haralampos M. Moutsopoulos of the National University of Athens. His contributions to patient care, teaching, and original research are legion. The papers that are included reflect not only a wide range of scholarship in autoimmunology, but importantly are written by his colleagues and friends, and by former students. They encompass original scholarship in Sjögren's syndrome, but also in a number of effector pathways in both adult and pediatric autoimmunology. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Conversion of autoimmune hypothyroidism to hyperthyroidism


    Furqan, Saira; Haque, Naeem-ul; Islam, Najmul


    Background Graves’ disease and Hashimoto’s thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. Case presentation We are reporting three cases of middle aged Asian female...

  13. Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders


    Ordookhani, Arash; Burman, Kenneth D.


    Context There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. Evidence Acquisition A comprehensive literature search was conducted employing MEDLINE database. T...

  14. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Ana M. C. Faria


    Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.

  15. Pruritus in Autoimmune Connective Tissue Diseases. (United States)

    Smith, Gideon P; Argobi, Yahya


    Pruritus in autoimmune connective tissue diseases is a common symptom that can be severe and affect the quality of life of patients. It can be related to disease activity and severity or occur independent of the disease. Appropriate therapy to control the itch depends on the etiology, and it is therefore essential to first work-up these patients for the underlying trigger. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Putative bronchopulmonary flagellated protozoa in immunosuppressed patients. (United States)

    Kilimcioglu, Ali Ahmet; Havlucu, Yavuz; Girginkardesler, Nogay; Celik, Pınar; Yereli, Kor; Özbilgin, Ahmet


    Flagellated protozoa that cause bronchopulmonary symptoms in humans are commonly neglected. These protozoal forms which were presumed to be "flagellated protozoa" have been previously identified in immunosuppressed patients in a number of studies, but have not been certainly classified so far. Since no human cases of bronchopulmonary flagellated protozoa were reported from Turkey, we aimed to investigate these putative protozoa in immunosuppressed patients who are particularly at risk of infectious diseases. Bronchoalveolar lavage fluid samples of 110 immunosuppressed adult patients who were admitted to the Department of Chest Diseases, Hafsa Sultan Hospital of Celal Bayar University, Manisa, Turkey, were examined in terms of parasites by light microscopy. Flagellated protozoal forms were detected in nine (8.2%) of 110 cases. Metronidazole (500 mg b.i.d. for 30 days) was given to all positive cases and a second bronchoscopy was performed at the end of the treatment, which revealed no parasites. In conclusion, immunosuppressed patients with bronchopulmonary symptoms should attentively be examined with regard to flagellated protozoa which can easily be misidentified as epithelial cells.

  17. Toddlers’ Duration of Attention towards Putative Threat (United States)

    Kiel, Elizabeth J.; Buss, Kristin A.


    Although individual differences in reactions to novelty in the toddler years have been consistently linked to risk for developing anxious behavior, toddlers’ attention towards a novel, putatively threatening stimulus while in the presence of other enjoyable activities has rarely been examined as a precursor to such risk. The current study examined how attention towards an angry-looking gorilla mask in a room with alternative opportunities for play in 24-month-old toddlers predicted social inhibition when children entered kindergarten. Analyses examined attention to threat above and beyond and in interaction with both proximity to the mask and fear of novelty observed in other situations. Attention to threat interacted with proximity to the mask to predict social inhibition, such that attention to threat most strongly predicted social inhibition when toddlers stayed furthest from the mask. This relation occurred above and beyond the predictive relation between fear of novelty and social inhibition. Results are discussed within the broader literature of anxiety development and attentional processes in young children. PMID:21373365

  18. Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome. (United States)

    Pamfil, Cristina; Candrea, Elisabeta; Berki, Emese; Popov, Horațiu I; Radu, Pompilia I; Rednic, Simona


    Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

  19. In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation. (United States)

    Maes, Michael; Ringel, Karl; Kubera, Marta; Anderson, George; Morris, Gerwyn; Galecki, Piotr; Geffard, Michel


    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation. We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale). The incidence of positive autoimmune activity against 5-HT was significantly higher (pfatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise. The results show that, in ME/CFS, increased 5-HT autoimmune activity is associated with activation of immuno-inflammatory pathways and increased bacterial translocation, factors which are known to play a role in the onset of autoimmune reactions. 5-HT autoimmune activity could play a role in the pathophysiology of ME/CFS and the onset of physio-somatic symptoms. These results provide mechanistic support for the notion that ME/CFS is a neuro-immune disorder. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Resilience in women with autoimmune rheumatic diseases. (United States)

    Rojas, Manuel; Rodriguez, Yhojan; Pacheco, Yovana; Zapata, Elizabeth; Monsalve, Diana M; Mantilla, Rubén D; Rodríguez-Jimenez, Monica; Ramírez-Santana, Carolina; Molano-González, Nicolás; Anaya, Juan-Manuel


    To evaluate the relationship between resilience and clinical outcomes in patients with autoimmune rheumatic diseases. Focus groups, individual interviews, and chart reviews were done to collect data on 188 women with autoimmune rheumatic diseases, namely rheumatoid arthritis (n=51), systemic lupus erythematosus (n=70), systemic sclerosis (n=35), and Sjögren's syndrome (n=32). Demographic, clinical, and laboratory variables were assessed including disease activity by patient reported outcomes. Resilience was evaluated by using the Brief Resilience Scale. Bivariate, multiple linear regression, and classification and regression trees were used to analyse data. Resilience was influenced by age, duration of disease, and socioeconomic status. Lower resilience scores were observed in younger patients (50years) had higher resilience scores regardless of socioeconomic status. There was no influence of disease activity on resilience. A particular behaviour was observed in systemic sclerosis in which patients with high socioeconomic status and regular physical activity had higher resilience scores. Resilience in patients with autoimmune rheumatic diseases is a continuum process influenced by age and socioeconomic status. The ways in which these variables along with exercise influence resilience deserve further investigation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  1. Experimental models of autoimmune inflammatory ocular diseases

    Directory of Open Access Journals (Sweden)

    Fabio Gasparin


    Full Text Available Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin. Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

  2. Alcoholic Cirrhosis Increases Risk for Autoimmune Diseases

    DEFF Research Database (Denmark)

    Grønbæk, Lisbet; Vilstrup, Hendrik; Deleuran, Bent


    IRR, 1.56; 95% CI, 1.26-1.92), celiac disease (aIRR, 5.12; 95% CI, 2.58-10.16), pernicious anemia (aIRR, 2.35; 95% CI, 1.50-3.68), and psoriasis (aIRR, 4.06; 95% CI, 3.32-4.97). There was no increase in the incidence rate for rheumatoid arthritis (aIRR, 0.89; 95% CI, 0.69-1.15); the incidence rate......BACKGROUND & AIMS: Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients...... (controls) of the same sex and age. The incidence rates of various autoimmune diseases were compared between patients with cirrhosis and controls and adjusted for the number of hospitalizations in the previous year (a marker for the frequency of clinical examination). RESULTS: Of the 24,679 patients...

  3. Automation, consolidation, and integration in autoimmune diagnostics. (United States)

    Tozzoli, Renato; D'Aurizio, Federica; Villalta, Danilo; Bizzaro, Nicola


    Over the past two decades, we have witnessed an extraordinary change in autoimmune diagnostics, characterized by the progressive evolution of analytical technologies, the availability of new tests, and the explosive growth of molecular biology and proteomics. Aside from these huge improvements, organizational changes have also occurred which brought about a more modern vision of the autoimmune laboratory. The introduction of automation (for harmonization of testing, reduction of human error, reduction of handling steps, increase of productivity, decrease of turnaround time, improvement of safety), consolidation (combining different analytical technologies or strategies on one instrument or on one group of connected instruments) and integration (linking analytical instruments or group of instruments with pre- and post-analytical devices) opened a new era in immunodiagnostics. In this article, we review the most important changes that have occurred in autoimmune diagnostics and present some models related to the introduction of automation in the autoimmunology laboratory, such as automated indirect immunofluorescence and changes in the two-step strategy for detection of autoantibodies; automated monoplex immunoassays and reduction of turnaround time; and automated multiplex immunoassays for autoantibody profiling.

  4. Stem cell therapy for severe autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Marmont Alberto M.


    Full Text Available Intense immunosuppresion followed by alogenic or autogenic hematopoietic stem cell transplantation is a relatively recent procedure which was used for the first time in severe, refractory cases of systemic lupus erythematosus. Currently three agressive procedures are used in the treatment of autoimmune diseases: high dose chemotherapy without stem cell rescue, intense immunosuppression with subsequent infusion of the alogenic hematopoietic stem cell transplantation combined with or without the selection of CD34+ cells, and the autogenic hematopoietic stem cell transplantation. Proof of the graft-versus-leukemia effect observed define SCT as a form of immunotherapy, with additional evidence of an similar Graft-vs-Autoimmunity effect which is suggestive of a cure for autoimmune diseases in this type of therapy. The use of alogenic SCT improved due to its safety compared to autogenic transplantations. In this report, data of multiply sclerosis and systemic lupus erythematosus are reported, with the conclusion that Immunoablation followed by SCT is clearly indicated in such cases.

  5. Thyroid storm and warm autoimmune hemolytic anemia. (United States)

    Moore, Joseph A; Gliga, Louise; Nagalla, Srikanth


    Graves' disease is often associated with other autoimmune disorders, including rare associations with autoimmune hemolytic anemia (AIHA). We describe a unique presentation of thyroid storm and warm AIHA diagnosed concurrently in a young female with hyperthyroidism. The patient presented with nausea, vomiting, diarrhea and altered mental status. Laboratory studies revealed hemoglobin 3.9g/dL, platelets 171×10 9 L -1 , haptoglobin storm and warm AIHA. She was started on glucocorticoids to treat both warm AIHA and thyroid storm, as well as antithyroid medications, propranolol and folic acid. Due to profound anemia and hemodynamic instability, the patient was transfused two units of uncrossmatched packed red blood cells slowly and tolerated this well. She was discharged on methimazole as well as a prolonged prednisone taper, and achieved complete resolution of the thyrotoxicosis and anemia at one month. Hyperthyroidism can affect all three blood cell lineages of the hematopoietic system. Anemia can be seen in 10-20% of patients with thyrotoxicosis. Several autoimmune processes can lead to anemia in Graves' disease, including pernicious anemia, celiac disease, and warm AIHA. This case illustrates a rarely described presentation of a patient with Graves' disease presenting with concurrent thyroid storm and warm AIHA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Autoimmune thyroiditis associated with neuromyelitis optica (NMO

    Directory of Open Access Journals (Sweden)

    Sudulagunta, Sreenivasa Rao


    Full Text Available Neuromyelitis optica (NMO or Devic’s syndrome is a rare relapsing demyelinating disease of the central nervous system (CNS that mainly affects the spinal cord and optic nerves and shares many clinical and radiological features with multiple sclerosis. The association of NMO with other autoimmune diseases was reported, but very few reports described association with autoimmune thyroid disease. Early differentiation between NMO and multiple sclerosis is very important as the natural course and treatment regimens differ significantly. We report a case of a 50-year-old woman who was admitted initially with vomiting, hiccups and paraesthesias but was not diagnosed with NMO and presented with a severe progression of the disease. The patient was also diagnosed to have autoimmune thyroiditis with lymphocytic infiltration of the thyroid which progressed from hyperthyroidism to hypothyroidism. NMO diagnosis was established with seropositivity for NMO-IgG and MRI showing longitudinally extensive spinal cord lesions (3 or more spinal segments. In spite of treatment, the response was poor due to lack of early diagnosis and aggressive immunosuppressant therapy.

  7. The dopaminergic system in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Rodrigo ePacheco


    Full Text Available Bidirectional interactions between the immune and the nervous systems are of considerable interest both for deciphering their functioning and for designing novel therapeutic strategies. The past decade has brought a burst of insights into the molecular mechanisms involved in neuro-immune communications mediated by dopamine. Studies of dendritic cells (DCs revealed that they express the whole machinery to synthesize and store dopamine, which may act in an autocrine manner to stimulate dopamine receptors (DARs. Depending on specific DARs stimulated on DCs and T cells, dopamine may differentially favor CD4+ T cell differentiation into Th1 or Th17 inflammatory cells. Regulatory T cells can also release high amounts of dopamine that acts in an autocrine DAR-mediated manner to inhibit their suppressive activity. These dopaminergic regulations could represent a driving force during autoimmunity. Indeed, dopamine levels are altered in the brain of mouse models of multiple sclerosis (MS and lupus, and in inflamed tissues of patients with inflammatory bowel diseases or rheumatoid arthritis. The distorted expression of DARs in peripheral lymphocytes of lupus and MS patients also supports the importance of dopaminergic regulations in autoimmunity. Moreover, dopamine analogs had beneficial therapeutic effects in animal models, and in patients with lupus or rheumatoid arthritis. We propose models that may underlie key roles of dopamine and its receptors in autoimmune diseases.

  8. Autonomous Byte Stream Randomizer (United States)

    Paloulian, George K.; Woo, Simon S.; Chow, Edward T.


    Net-centric networking environments are often faced with limited resources and must utilize bandwidth as efficiently as possible. In networking environments that span wide areas, the data transmission has to be efficient without any redundant or exuberant metadata. The Autonomous Byte Stream Randomizer software provides an extra level of security on top of existing data encryption methods. Randomizing the data s byte stream adds an extra layer to existing data protection methods, thus making it harder for an attacker to decrypt protected data. Based on a generated crypto-graphically secure random seed, a random sequence of numbers is used to intelligently and efficiently swap the organization of bytes in data using the unbiased and memory-efficient in-place Fisher-Yates shuffle method. Swapping bytes and reorganizing the crucial structure of the byte data renders the data file unreadable and leaves the data in a deconstructed state. This deconstruction adds an extra level of security requiring the byte stream to be reconstructed with the random seed in order to be readable. Once the data byte stream has been randomized, the software enables the data to be distributed to N nodes in an environment. Each piece of the data in randomized and distributed form is a separate entity unreadable on its own right, but when combined with all N pieces, is able to be reconstructed back to one. Reconstruction requires possession of the key used for randomizing the bytes, leading to the generation of the same cryptographically secure random sequence of numbers used to randomize the data. This software is a cornerstone capability possessing the ability to generate the same cryptographically secure sequence on different machines and time intervals, thus allowing this software to be used more heavily in net-centric environments where data transfer bandwidth is limited.

  9. Autoimmunity in Arabidopsis acd11 Is Mediated by Epigenetic Regulation of an Immune Receptor

    DEFF Research Database (Denmark)

    Palma, K.; Thorgrimsen, S.; Malinovsky, F.G.


    Certain pathogens deliver effectors into plant cells to modify host protein targets and thereby suppress immunity. These target modifications can be detected by intracellular immune receptors, or Resistance (R) proteins, that trigger strong immune responses including localized host cell death....... The accelerated cell death 11 (acd11) "lesion mimic" mutant of Arabidopsis thaliana exhibits autoimmune phenotypes such as constitutive defense responses and cell death without pathogen perception. ACD11 encodes a putative sphingosine transfer protein, but its precise role during these processes is unknown......, and that cell death in other lesion mimic mutants may also be caused by inappropriate activation of R genes. Moreover, SDG8 is required for basal and R protein-mediated pathogen resistance in Arabidopsis, revealing the importance of chromatin remodeling as a key process in plant innate immunity....

  10. Compact autonomous navigation system (CANS) (United States)

    Hao, Y. C.; Ying, L.; Xiong, K.; Cheng, H. Y.; Qiao, G. D.


    Autonomous navigation of Satellite and constellation has series of benefits, such as to reduce operation cost and ground station workload, to avoid the event of crises of war and natural disaster, to increase spacecraft autonomy, and so on. Autonomous navigation satellite is independent of ground station support. Many systems are developed for autonomous navigation of satellite in the past 20 years. Along them American MANS (Microcosm Autonomous Navigation System) [1] of Microcosm Inc. and ERADS [2] [3] (Earth Reference Attitude Determination System) of Honeywell Inc. are well known. The systems anticipate a series of good features of autonomous navigation and aim low cost, integrated structure, low power consumption and compact layout. The ERADS is an integrated small 3-axis attitude sensor system with low cost and small volume. It has the Earth center measurement accuracy higher than the common IR sensor because the detected ultraviolet radiation zone of the atmosphere has a brightness gradient larger than that of the IR zone. But the ERADS is still a complex system because it has to eliminate many problems such as making of the sapphire sphere lens, birefringence effect of sapphire, high precision image transfer optical fiber flattener, ultraviolet intensifier noise, and so on. The marginal sphere FOV of the sphere lens of the ERADS is used to star imaging that may be bring some disadvantages., i.e. , the image energy and attitude measurements accuracy may be reduced due to the tilt image acceptance end of the fiber flattener in the FOV. Besides Japan, Germany and Russia developed visible earth sensor for GEO [4] [5]. Do we have a way to develop a cheaper/easier and more accurate autonomous navigation system that can be used to all LEO spacecraft, especially, to LEO small and micro satellites? To return this problem we provide a new type of the system—CANS (Compact Autonomous Navigation System) [6].

  11. Twenty putative palmitoyl-acyl transferase genes with distinct ...

    African Journals Online (AJOL)

    There are 20 genes containing DHHC domain predicted to encode putative palmitoyltransferase in Arabidopsis thaliana genome. However, little is known about their characteristics such as genetic relationship and expression profile. Here, we present an overview of the putative PAT genes in A. thaliana focusing on their ...

  12. Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population.

    Directory of Open Access Journals (Sweden)

    Zhiyuan Zhao

    Full Text Available The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA amongst patients with type 1 diabetes (T1D and autoimmune thyroid disease (AITD in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v. The study also included 145 patients with type 2 diabetes (T2D, 97 patients with non-autoimmune thyroid disease (NAITD, and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001 or NAITD (3.1%; P < 0.0001 or healthy controls (1%; p<0.0001. The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040 or with AITD alone (p = 0.017. T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients.

  13. Putative radioresistant bacterial isolate from sewage water

    International Nuclear Information System (INIS)

    Ang, April; Chua, Patricia; Perez, Kristine; Rey, April; Rivor Kristel; San Pablo, Czarina; Santos, Ernestine


    Sewage water was collected from a stagnant body of water in Balara, Quezon City. approximately 150 ml was aseptically transferred into eight Erlenmeyer flasks. Seven flasks were then subjected to different doses of radiation at the 60 Co irradiation facility, PNRI (Philippine Nuclear Research Institute) which are as follows: 0.01 kGy, 0.1 kGy, 0.5 kGy, 1 kGy, 5 kGy, 10 kGy, and 15 kGy. The remaining flask was used as the control. After irradiation, all the different treatments were subjected to colony count at the culture collection laboratory, NSRI. Results showed that the colonies from sewage water treatments irradiated at 0.01 kGy (treatment A), 0.10 kGy (treatment B), and 0.50 kGy (treatment C) exhibited a decreasing trend with colony counts 4.60 x 10 3 CFU/ml, and 1.30 x 10 3 CFU/ml, and 26 CFU/ml, respectively. Contrastingly, at 1 kGy (treatment D), high colony count of 2.95 x 10 3 CFU/ml was observed which is even higher compared to the control (1.02 x 10 3 CFU/ml). Treatment E that was irradiated at 5 kGy manifested low survival rate (25 CFU/ml) indicating the presence of few putative intermediate radioresistant bacteria. Radiation dose treatments higher than 5 kGy (i.e., 10 kGy and 15 kGy) exhibited no bacterial survival. (Author)

  14. Putative radioresistant bacterial isolate from sewage water

    Energy Technology Data Exchange (ETDEWEB)

    Ang, April; Chua, Patricia; Perez, Kristine; Rey, April; Kristel, Rivor; San Pablo, Czarina; Santos, Ernestine


    Sewage water was collected from a stagnant body of water in Balara, Quezon City. approximately 150 ml was aseptically transferred into eight Erlenmeyer flasks. Seven flasks were then subjected to different doses of radiation at the {sup 60}Co irradiation facility, PNRI (Philippine Nuclear Research Institute) which are as follows: 0.01 kGy, 0.1 kGy, 0.5 kGy, 1 kGy, 5 kGy, 10 kGy, and 15 kGy. The remaining flask was used as the control. After irradiation, all the different treatments were subjected to colony count at the culture collection laboratory, NSRI. Results showed that the colonies from sewage water treatments irradiated at 0.01 kGy (treatment A), 0.10 kGy (treatment B), and 0.50 kGy (treatment C) exhibited a decreasing trend with colony counts 4.60 x 10{sup 3} CFU/ml, and 1.30 x 10{sup 3} CFU/ml, and 26 CFU/ml, respectively. Contrastingly, at 1 kGy (treatment D), high colony count of 2.95 x 10{sup 3} CFU/ml was observed which is even higher compared to the control (1.02 x 10{sup 3} CFU/ml). Treatment E that was irradiated at 5 kGy manifested low survival rate (25 CFU/ml) indicating the presence of few putative intermediate radioresistant bacteria. Radiation dose treatments higher than 5 kGy (i.e., 10 kGy and 15 kGy) exhibited no bacterial survival. (Author)

  15. Autoimmune disease prevalence in a multiple sclerosis cohort in Argentina. (United States)

    Farez, Mauricio F; Balbuena Aguirre, María E; Varela, Francisco; Köhler, Alejandro A; Correale, Jorge


    Background. Comorbid autoimmune diseases in MS patients have been studied extensively with controversial results. Moreover, no such data exists for Latin-American MS patients. Methods. We conducted a case-control study aimed to establish the prevalence of autoimmune disorders in a cohort of Argentinean MS patients. Results. There were no significant differences in autoimmune disease prevalence in MS patients with respect to controls. The presence of one or more autoimmune disorders did not increase risk of MS (OR 0.85, 95% CI 0.6-1.3). Discussion. Our results indicate absence of increased comorbid autoimmune disease prevalence in MS patients, as well as of increased risk of MS in patients suffering from other autoimmune disorders.

  16. Autonomous Landing on Moving Platforms

    KAUST Repository

    Mendoza Chavez, Gilberto


    This thesis investigates autonomous landing of a micro air vehicle (MAV) on a nonstationary ground platform. Unmanned aerial vehicles (UAVs) and micro air vehicles (MAVs) are becoming every day more ubiquitous. Nonetheless, many applications still require specialized human pilots or supervisors. Current research is focusing on augmenting the scope of tasks that these vehicles are able to accomplish autonomously. Precise autonomous landing on moving platforms is essential for self-deployment and recovery of MAVs, but it remains a challenging task for both autonomous and piloted vehicles. Model Predictive Control (MPC) is a widely used and effective scheme to control constrained systems. One of its variants, output-feedback tube-based MPC, ensures robust stability for systems with bounded disturbances under system state reconstruction. This thesis proposes a MAV control strategy based on this variant of MPC to perform rapid and precise autonomous landing on moving targets whose nominal (uncommitted) trajectory and velocity are slowly varying. The proposed approach is demonstrated on an experimental setup.

  17. Regulatory T-cells in autoimmune diseases: challenges, controversies and--yet--unanswered questions. (United States)

    Grant, Charlotte R; Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego; Longhi, Maria Serena


    Regulatory T cells (Tregs) are central to the maintenance of self-tolerance and tissue homeostasis. Markers commonly used to define human Tregs in the research setting include high expression of CD25, FOXP3 positivity and low expression/negativity for CD127. Many other markers have been proposed, but none unequivocally identifies bona fide Tregs. Tregs are equipped with an array of mechanisms of suppression, including the modulation of antigen presenting cell maturation and function, the killing of target cells, the disruption of metabolic pathways and the production of anti-inflammatory cytokines. Treg impairment has been reported in a number of human autoimmune conditions and includes Treg numerical and functional defects and conversion into effector cells in response to inflammation. In addition to intrinsic Treg impairment, resistance of effector T cells to Treg control has been described. Discrepancies in the literature are common, reflecting differences in the choice of study participants and the technical challenges associated with investigating this cell population. Studies differ in terms of the methodology used to define and isolate putative regulatory cells and to assess their suppressive function. In this review we outline studies describing Treg frequency and suppressive function in systemic and organ specific autoimmune diseases, with a specific focus on the challenges faced when investigating Tregs in these conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Involvement of chronic epipharyngitis in autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). (United States)

    Hotta, Osamu; Tanaka, Ayaki; Torigoe, Akira; Imai, Kazuaki; Ieiri, Norio


    The epipharynx is an immunologically active site even under normal conditions, and enhanced immunologic activation is prone to occur in response to an upper respiratory infection, air pollution, and possibly to vaccine adjuvants. Due to the potential link between the central nervous system and immune function, a relationship between epipharyngitis and autonomic nervous disturbance as well as autoimmune disease has been suggested. Various functional somatic symptoms have been described after human papillomavirus (HPV) vaccination, although a causal relationship has not been established. We examined the epipharynx in young women showing functional somatic symptoms following HPV vaccination. Surprisingly, despite having minimal symptoms involving the pharynx, all patients were found to have severe epipharyngitis. In addition, significant improvement in symptoms was seen in most patients who underwent epipharyngeal treatment. Thus, we speculate that the chronic epipharyngitis potentially caused by the vaccine adjuvant may be involved in the pathogenesis of functional somatic syndrome (FSS) post-HPV vaccination. Further, we suggest that epipharyngeal treatment may be effective for various types of FSS regardless of the initial cause, as well as for some autoimmune diseases, and that this may be an important direction in future research.

  19. The Bering Autonomous Target Detection

    DEFF Research Database (Denmark)

    Jørgensen, John Leif; Denver, Troelz; Betto, Maurizio


    An autonomous asteroid target detection and tracking method has been developed. The method features near omnidirectionality and focus on high speed operations and completeness of search of the near space rather than the traditional faint object search methods, employed presently at the larger...... telescopes. The method has proven robust in operation and is well suited for use onboard spacecraft. As development target for the method and the associated instrumentation the asteroid research mission Bering has been used. Onboard a spacecraft, the autonomous detection is centered around the fully...... autonomous star tracker the Advanced Stellar Compass (ASC). One feature of this instrument is that potential targets are registered directly in terms of date, right ascension, declination, and intensity, which greatly facilitates both tracking search and registering. Results from ground and inflight tests...

  20. Autonomous Industrial Mobile Manipulation (AIMM)

    DEFF Research Database (Denmark)

    Hvilshøj, Mads; Bøgh, Simon; Nielsen, Oluf Skov


    Purpose - The purpose of this paper is to provide a review of the interdisciplinary research field Autonomous Industrial Mobile Manipulation (AIMM), with an emphasis on physical implementations and applications. Design/methodology/approach - Following an introduction to AIMM, this paper investiga......Purpose - The purpose of this paper is to provide a review of the interdisciplinary research field Autonomous Industrial Mobile Manipulation (AIMM), with an emphasis on physical implementations and applications. Design/methodology/approach - Following an introduction to AIMM, this paper......; sustainability, configuration, adaptation, autonomy, positioning, manipulation and grasping, robot-robot interaction, human-robot interaction, process quality, dependability, and physical properties. Findings - The concise yet comprehensive review provides both researchers (academia) and practitioners (industry......) with a quick and gentle overview of AIMM. Furthermore, the paper identifies key open issues and promising research directions to realize real-world integration and maturation of the AIMM technology. Originality/value - This paper reviews the interdisciplinary research field Autonomous Industrial Mobile...

  1. [Animal models of autoimmune prostatitis and their evaluation criteria]. (United States)

    Shen, Jia-ming; Lu, Jin-chun; Yao, Bing


    Chronic prostatitis is a highly prevalent disease of unclear etiology. Researches show that autoimmune reaction is one cause of the problem. An effective animal model may help a lot to understand the pathogenesis and find proper diagnostic and therapeutic strategies of the disease. Currently used autoimmune prostatitis-related animal models include those of age-dependent spontaneous prostatitis, autoimmune regulator-dependent spontaneous prostatitis, self antigen-induced prostatitis, and steroid-induced prostatitis. Whether an animal model of autoimmune prostatitis is successfully established can be evaluated mainly from the five aspects: histology, morphology, specific antigens, inflammatory factors, and pain intensity.

  2. Autoimmunity and primary immunodeficiency: two sides of the same coin? (United States)

    Schmidt, Reinhold E; Grimbacher, Bodo; Witte, Torsten


    Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions; however, increased understanding of the complex immune regulatory and signalling mechanisms involved, coupled with the application of genetic analysis, is revealing the complex relationships between primary immunodeficiency syndromes and autoimmune diseases. Single-gene defects can cause rare diseases that predominantly present with autoimmune symptoms. Such genetic defects also predispose individuals to recurrent infections (a hallmark of immunodeficiency) and can cause primary immunodeficiencies, which can also lead to immune dysregulation and autoimmunity. Moreover, risk factors for polygenic rheumatic diseases often exist in the same genes as the mutations that give rise to primary immunodeficiency syndromes. In this Review, various primary immunodeficiency syndromes are presented, along with their pathogenetic mechanisms and relationship to autoimmune diseases, in an effort to increase awareness of immunodeficiencies that occur concurrently with autoimmune diseases and to highlight the need to initiate appropriate genetic tests. The growing knowledge of various genetically determined pathologic mechanisms in patients with immunodeficiencies who have autoimmune symptoms opens up new avenues for personalized molecular therapies that could potentially treat immunodeficiency and autoimmunity at the same time, and that could be further explored in the context of autoimmune rheumatic diseases.

  3. Transient Non-Autoimmune Hyperthyroidism of Early Pregnancy

    Directory of Open Access Journals (Sweden)

    Alexander M. Goldman


    Full Text Available It is characterized by chemical and sometimes clinical hyperthyroidism, without evidence of thyroid autoimmunity that resolves spontaneously by 16 weeks gestation without significant obstetrical complications.

  4. Achalasia in a Patient with Polyglandular Autoimmune Syndrome Type II

    Directory of Open Access Journals (Sweden)

    Bashar S. Amr


    Full Text Available Achalasia is a rare disease characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter to relax. The etiology of this disease remains unknown. Polyglandular autoimmune syndrome type II is a well-identified disease characterized by the occurrence of autoimmune Addison's disease in combination with autoimmune thyroid disease and/or type 1 diabetes mellitus. We report a case that suggests autoimmunity and immunogenicity as a probable contributing factor for association of these two rare disorders.

  5. Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population. (United States)

    Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael


    Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected.

  6. Epigenetics of Autoantigens: New Opportunities for Therapy of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Marko Radic


    Full Text Available The field of epigenetics requires that traditional divisions between scientific disciplines give way to cross-fertilization of concepts and ideas from different areas of investigation. Such is the case with research in autoimmunity. Recent discoveries of stimuli that induce autoimmunity reveal that epigenetic marks of autoantigens are recognized by autoreactive B and T cell receptors. Thus, insights into the initiation of autoimmunity, its prevention and therapy will arise from understanding the biochemistry, cell biology and microbiology of autoantigen epigenetics. Here, we highlight potential benefits from the inhibition of a histone modifying enzyme and the administration of a phosphorylated, spliceosome-derived peptide, in the treatment of autoimmunity.

  7. Autonomic Regulation of Splanchnic Circulation

    Directory of Open Access Journals (Sweden)

    Kathleen A Fraser


    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  8. Political accountability and autonomous weapons

    Directory of Open Access Journals (Sweden)

    James Igoe Walsh


    Full Text Available Autonomous weapons would have the capacity to select and attack targets without direct human input. One important objection to the introduction of such weapons is that they will make it more difficult to identify and hold accountable those responsible for undesirable outcomes such as mission failures and civilian casualties. I hypothesize that individuals can modify their attribution of responsibility in predicable ways to accommodate this new technology. The results of a survey experiment are consistent with this; subjects continue to find responsible and hold accountable political and military leaders when autonomous weapons are used, but also attribute responsibility to the designers and programmers of such weapons.

  9. Discerning non-autonomous dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Clemson, Philip T.; Stefanovska, Aneta, E-mail:


    Structure and function go hand in hand. However, while a complex structure can be relatively safely broken down into the minutest parts, and technology is now delving into nanoscales, the function of complex systems requires a completely different approach. Here the complexity clearly arises from nonlinear interactions, which prevents us from obtaining a realistic description of a system by dissecting it into its structural component parts. At best, the result of such investigations does not substantially add to our understanding or at worst it can even be misleading. Not surprisingly, the dynamics of complex systems, facilitated by increasing computational efficiency, is now readily tackled in the case of measured time series. Moreover, time series can now be collected in practically every branch of science and in any structural scale—from protein dynamics in a living cell to data collected in astrophysics or even via social networks. In searching for deterministic patterns in such data we are limited by the fact that no complex system in the real world is autonomous. Hence, as an alternative to the stochastic approach that is predominantly applied to data from inherently non-autonomous complex systems, theory and methods specifically tailored to non-autonomous systems are needed. Indeed, in the last decade we have faced a huge advance in mathematical methods, including the introduction of pullback attractors, as well as time series methods that cope with the most important characteristic of non-autonomous systems—their time-dependent behaviour. Here we review current methods for the analysis of non-autonomous dynamics including those for extracting properties of interactions and the direction of couplings. We illustrate each method by applying it to three sets of systems typical for chaotic, stochastic and non-autonomous behaviour. For the chaotic class we select the Lorenz system, for the stochastic the noise-forced Duffing system and for the non-autonomous

  10. Gas House Autonomous System Monitoring (United States)

    Miller, Luke; Edsall, Ashley


    Gas House Autonomous System Monitoring (GHASM) will employ Integrated System Health Monitoring (ISHM) of cryogenic fluids in the High Pressure Gas Facility at Stennis Space Center. The preliminary focus of development incorporates the passive monitoring and eventual commanding of the Nitrogen System. ISHM offers generic system awareness, adept at using concepts rather than specific error cases. As an enabler for autonomy, ISHM provides capabilities inclusive of anomaly detection, diagnosis, and abnormality prediction. Advancing ISHM and Autonomous Operation functional capabilities enhances quality of data, optimizes safety, improves cost effectiveness, and has direct benefits to a wide spectrum of aerospace applications.

  11. Discerning non-autonomous dynamics

    International Nuclear Information System (INIS)

    Clemson, Philip T.; Stefanovska, Aneta


    Structure and function go hand in hand. However, while a complex structure can be relatively safely broken down into the minutest parts, and technology is now delving into nanoscales, the function of complex systems requires a completely different approach. Here the complexity clearly arises from nonlinear interactions, which prevents us from obtaining a realistic description of a system by dissecting it into its structural component parts. At best, the result of such investigations does not substantially add to our understanding or at worst it can even be misleading. Not surprisingly, the dynamics of complex systems, facilitated by increasing computational efficiency, is now readily tackled in the case of measured time series. Moreover, time series can now be collected in practically every branch of science and in any structural scale—from protein dynamics in a living cell to data collected in astrophysics or even via social networks. In searching for deterministic patterns in such data we are limited by the fact that no complex system in the real world is autonomous. Hence, as an alternative to the stochastic approach that is predominantly applied to data from inherently non-autonomous complex systems, theory and methods specifically tailored to non-autonomous systems are needed. Indeed, in the last decade we have faced a huge advance in mathematical methods, including the introduction of pullback attractors, as well as time series methods that cope with the most important characteristic of non-autonomous systems—their time-dependent behaviour. Here we review current methods for the analysis of non-autonomous dynamics including those for extracting properties of interactions and the direction of couplings. We illustrate each method by applying it to three sets of systems typical for chaotic, stochastic and non-autonomous behaviour. For the chaotic class we select the Lorenz system, for the stochastic the noise-forced Duffing system and for the non-autonomous

  12. Autoimmune pancreatitis in Japan: overview and perspective. (United States)

    Shimosegawa, Tooru; Kanno, Atsushi


    Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, i.e., association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjögren's syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjögren's syndrome or PSC. Now the concept of "IgG4-related sclerosing disease" has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called "idiopathic duct-centric chronic pancreatitis (IDCP)" and "AIP with granulocyte epithelial lesion (GEL)" and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease.

  13. Autoimmune pancreatitis in Japan. Overview and perspective

    International Nuclear Information System (INIS)

    Shimosegawa, Tooru; Kanno, Atsushi


    Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, id est (i.e.), association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjogren's syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjogren's syndrome or PSC. Now the concept of 'IgG4-related sclerosing disease' has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called 'idiopathic duct-centric chronic pancreatitis (IDCP)' and AIP with granulocyte epithelial lesion (GEL)' and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease. (author)

  14. Cardiac autonomic regulation is disturbed in children with euthyroid Hashimoto thyroiditis. (United States)

    Kilic, Ayhan; Gulgun, Mustafa; Tascilar, Mehmet Emre; Sari, Erkan; Yokusoglu, Mehmet


    Hashimoto thyroiditis (chronic autoimmune thyroiditis) is the most common form of thyroiditis in childhood. Previous studies have found autonomic dysfunction of varying magnitude in patients with autoimmune diseases, which is considered a cardiovascular risk factor. We aimed to evaluate the heart rate variability (HRV), a measure of cardiac autonomic modulation, in children with euthyroid Hashimoto thyroiditis (eHT). The study included 32 patients with eHT (27 girls and 5 boys; mean age 11 ± 4.1 years, range 8-16; body mass index 0.47 ± 0.69 kg/m(2)), as judged by normal or minimally elevated serum TSH levels (normal range: 0.34-5.6 mIU/l) and normal levels of free thyroid hormones (FT4 and FT3) and 38 euthyroid age-matched controls. Patients with eHT and control subjects underwent physical examination and 24-hour ambulatory ECG monitoring. Time-domain parameters of HRV were evaluated for cardiac autonomic functions. Children with eHT displayed significantly lower values of time-domain parameters of SDANN (standard deviation of the averages of NN intervals), RMSSD (square root of the mean of the sum of the squares of differences between adjacent NN intervals), NN50 counts (number of pairs of adjacent NN intervals differing by more than 50 ms) and PNN50 (NN50 count divided by the total number of all NN intervals) for each 5-min interval, compared to healthy controls (p < 0.05 for each), indicating the decreased beat-to-beat variation of heart rate. In conclusion, eHT is associated with disturbed autonomic regulation of heart rate. Hence, the children with eHT are at higher risk for developing cardiovascular diseases.

  15. Anti-Saccharomyces cerevisiae autoantibodies in autoimmune diseases: from bread baking to autoimmunity. (United States)

    Rinaldi, Maurizio; Perricone, Roberto; Blank, Miri; Perricone, Carlo; Shoenfeld, Yehuda


    Saccharomyces cerevisiae is best known as the baker's and brewer's yeast, but its residual traces are also frequent excipients in some vaccines. Although anti-S. cerevisiae autoantibodies (ASCAs) are considered specific for Crohn's disease, a growing number of studies have detected high levels of ASCAs in patients affected with autoimmune diseases as compared with healthy controls, including antiphospholipid syndrome, systemic lupus erythematosus, type 1 diabetes mellitus, and rheumatoid arthritis. Commensal microorganisms such as Saccharomyces are required for nutrition, proper development of Peyer's aggregated lymphoid tissue, and tissue healing. However, even the commensal nonclassically pathogenic microbiota can trigger autoimmunity when fine regulation of immune tolerance does not work properly. For our purposes, the protein database of the National Center for Biotechnology Information (NCBI) was consulted, comparing Saccharomyces mannan to several molecules with a pathogenetic role in autoimmune diseases. Thanks to the NCBI bioinformation technology tool, several overlaps in molecular structures (50-100 %) were identified when yeast mannan, and the most common autoantigens were compared. The autoantigen U2 snRNP B″ was found to conserve a superfamily protein domain that shares 83 % of the S. cerevisiae mannan sequence. Furthermore, ASCAs may be present years before the diagnosis of some associated autoimmune diseases as they were retrospectively found in the preserved blood samples of soldiers who became affected by Crohn's disease years later. Our results strongly suggest that ASCAs' role in clinical practice should be better addressed in order to evaluate their predictive or prognostic relevance.

  16. Airway Autoimmune Inflammatory Response (AAIR) Syndrome: An Asthma-Autoimmune Overlap Disorder? (United States)

    Spencer, Chantal Y; Millman, Jennifer; Veiga, Keila; Vicencio, Alfin G


    Asthma encompasses numerous phenotypes that may require alternate approaches to diagnosis and therapy, particularly for patients whose symptoms remain poorly controlled despite escalating treatment. We describe 3 patients with apparent asthma who demonstrated unusual findings on cryobiopsy by flexible bronchoscopy and responded to therapy directed against autoimmune disease. Copyright © 2018 by the American Academy of Pediatrics.

  17. De novo autoimmune hepatitis after liver transplantation. (United States)

    Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin


    The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin

  18. On immunological polymorphism of autoimmune thyroiditis

    International Nuclear Information System (INIS)

    Karachentsev, Yu.Yi.


    The study involved 46 persons. In the majority of patients the exposure dose was 0.155±0.01 Gy. Clinical, ultrasound, immunological, statistical and non-parametric methods were used. Considerable immunological polymorphism of autoimmune thyroiditis in the liquidators has been established; 1) with disturbances in the cellular immunity and low antithyroid antibody index, 2) without disturbances in the cellular immunity with positive indices of antithyroid antibodies, 3) with disturbances in cellular immunity and high indices of TH and MA antibodies

  19. Autonomic dysfunction in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Dümcke, Christine Winkler; Møller, Søren


    Liver cirrhosis and portal hypertension are frequently associated with signs of circulatory dysfunction and peripheral polyneuropathy, which includes defects of the autonomic nervous system. Autonomic dysfunction, which is seen in both alcoholic and non-alcoholic liver cirrhosis and increases...

  20. Energy homeostasis, autonomic activity and obesity

    NARCIS (Netherlands)

    Scheurink, AJW; Balkan, B; Nyakas, C; vanDijk, G; Steffens, AB; Bohus, B


    Obesity is often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The present paper summarizes the results of a number of studies designed to investigate autonomic functioning in normal, genetically, and experimentally obese rats, Particular emphasis is given

  1. Connected and autonomous vehicles 2040 vision. (United States)


    The Pennsylvania Department of Transportation (PennDOT) commissioned a one-year project, Connected and Autonomous : Vehicles 2040 Vision, with researchers at Carnegie Mellon University (CMU) to assess the implications of connected and : autonomous ve...

  2. Mining in the Future: Autonomous Robotics for Safer Mines

    CSIR Research Space (South Africa)

    Shahdi, A


    Full Text Available ? Require less support infrastructure ? Advanced sensors ? CSIR 2012 Slide 4 Degree of Autonomy ? Teleoperation ? Semi-autonomous ? Autonomous ? CSIR 2012 Slide 5 Mobile Intelligent Autonomous Systems Group ? The Mobile Intelligent Autonomous...

  3. Formal Verification of Autonomous Vehicle Platooning


    Kamali, Maryam; Dennis, Louise A.; McAree, Owen; Fisher, Michael; Veres, Sandor M.


    The coordination of multiple autonomous vehicles into convoys or platoons is expected on our highways in the near future. However, before such platoons can be deployed, the new autonomous behaviors of the vehicles in these platoons must be certified. An appropriate representation for vehicle platooning is as a multi-agent system in which each agent captures the "autonomous decisions" carried out by each vehicle. In order to ensure that these autonomous decision-making agents in vehicle platoo...

  4. Hazard Map for Autonomous Navigation

    DEFF Research Database (Denmark)

    Riis, Troels

    This dissertation describes the work performed in the area of using image analysis in the process of landing a spacecraft autonomously and safely on the surface of the Moon. This is suggested to be done using a Hazard Map. The correspondence problem between several Hazard Maps are investigated...

  5. Designing Assessment for Autonomous Learning (United States)

    Hay, Marie; Mathers, Lucy


    This paper aims to disseminate and evaluate an autonomous learning framework developed through collaborative research with first- and second-year undergraduate students at De Montfort University. Central to the framework is the involvement of students in the assessment of their peers and themselves using dialogue about the assessment and feedback…

  6. Computing architecture for autonomous microgrids (United States)

    Goldsmith, Steven Y.


    A computing architecture that facilitates autonomously controlling operations of a microgrid is described herein. A microgrid network includes numerous computing devices that execute intelligent agents, each of which is assigned to a particular entity (load, source, storage device, or switch) in the microgrid. The intelligent agents can execute in accordance with predefined protocols to collectively perform computations that facilitate uninterrupted control of the .

  7. Autonomous Landing on Moving Platforms

    KAUST Repository

    Mendoza Chavez, Gilberto


    -deployment and recovery of MAVs, but it remains a challenging task for both autonomous and piloted vehicles. Model Predictive Control (MPC) is a widely used and effective scheme to control constrained systems. One of its variants, output-feedback tube-based MPC, ensures

  8. Neuronal autoantibodies in epilepsy patients with peri-ictal autonomic findings. (United States)

    Baysal-Kirac, Leyla; Tuzun, Erdem; Erdag, Ece; Ulusoy, Canan; Vanli-Yavuz, Ebru Nur; Ekizoglu, Esme; Peach, Sian; Sezgin, Mine; Bebek, Nerses; Gurses, Candan; Gokyigit, Aysen; Vincent, Angela; Baykan, Betul


    Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3%) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29%), contactin-associated protein-like 2 (CASPR2) in 5 (29%), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18%), glutamic acid decarboxylase (GAD) in 2 (12%), glycine receptor (GLYR) in one (6%) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6%). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.

  9. The Role of Pathogenic Autoantibodies in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Merrill J. Rowley


    Full Text Available The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID. Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.

  10. Autoimmune hemolytic anemia: transfusion challenges and solutions

    Directory of Open Access Journals (Sweden)

    Barros MM


    Full Text Available Melca M O Barros, Dante M Langhi Jr, José O Bordin Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Autoimmune hemolytic anemia (AIHA is defined as the increased destruction of red blood cells (RBCs in the presence of anti-RBC autoantibodies and/or complement. Classification of AIHA is based on the optimal auto-RBC antibody reactivity temperatures and includes warm, cold-reactive, mixed AIHA, and drug-induced AIHA subtypes. AIHA is a rare disease, and recommendations for transfusion are based mainly on results from retrospective data and relatively small cohort studies, including heterogeneous patient samples or single case reports. In this article, we will review the challenges and solutions to safely transfuse AIHA patients. We will reflect on the indication for transfusion in AIHA and the difficulty in the accomplishment of immunohematological procedures for the selection of the safest and most compatible RBC units. Keywords: hemolytic anemia, RBC autoantibodies, autoimmunity, hemolysis, direct ­antiglobulin test

  11. Autoimmune pancreatitis can develop into chronic pancreatitis (United States)


    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

  12. Immunomodulation of Autoimmune Arthritis by Herbal CAM

    Directory of Open Access Journals (Sweden)

    Shivaprasad H. Venkatesha


    Full Text Available Rheumatoid arthritis (RA is a debilitating autoimmune disease of global prevalence. The disease is characterized by synovial inflammation leading to cartilage and bone damage. Most of the conventional drugs used for the treatment of RA have severe adverse reactions and are quite expensive. Over the years, increasing proportion of patients with RA and other immune disorders are resorting to complementary and alternative medicine (CAM for their health needs. Natural plant products comprise one of the most popular CAM for inflammatory and immune disorders. These herbal CAM belong to diverse traditional systems of medicine, including traditional Chinese medicine, Kampo, and Ayurvedic medicine. In this paper, we have outlined the major immunological pathways involved in the induction and regulation of autoimmune arthritis and described various herbal CAM that can effectively modulate these immune pathways. Most of the information about the mechanisms of action of herbal products in the experimental models of RA is relevant to arthritis patients as well. The study of immunological pathways coupled with the emerging application of genomics and proteomics in CAM research is likely to provide novel insights into the mechanisms of action of different CAM modalities.

  13. Advances in treatment of autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    LI Ji


    Full Text Available Autoimmune pancreatitis (AIP is a type of chronic pancreatitis characterized by an autoimmune inflammatory process. Treatment protocols for AIP are still evolving. According to the articles about AIP treatment in recent years, the indications for steroid therapy include specific clinical manifestations (jaundice, abdominal pain, etc., markedly abnormal imaging findings, and extrapancreatic organ involvement. The initial dose of steroid (prednisone is usually 0.6 mg·kg-1·d-1 or 30-40 mg/d; after 3 weeks to 1 month of treatment with the initial dose, the dose is decreased by 5-10 mg every 1-2 weeks until it drops to 2.5-5 mg/d; this dose is maintained for 6 months to 3 years. No consensus has been reached on the adverse effect of steroid on diabetes mellitus complicating AIP. Immunosuppressive agents should be used for the patients with disease relapses or with important extrapancreatic organs involved. Rituximab might become one of the therapies for refractory AIP. Although some patients achieved remission after surgical treatment, surgery is still not recommended as a routine treatment protocol due to the complications after surgery.

  14. Conversion of autoimmune hypothyroidism to hyperthyroidism. (United States)

    Furqan, Saira; Haque, Naeem-ul; Islam, Najmul


    Graves' disease and Hashimoto's thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone.

  15. Imaging B lymphocytes in autoimmune inflammatory diseases

    International Nuclear Information System (INIS)

    Iodice, V.; Lauri, C.; Capriotti, G.; Lagana', B.; Germano, V.; D’Amelio, R.; Picchianti Diamanti, A.


    B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasma cells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients

  16. [Autoimmune Encephalitis Associated with Malignant Tumors]. (United States)

    Inuzuka, Takashi


    Autoimmune encephalitis consists of limbic symptoms and signs associated with antibodies against neuronal cell-surface antigens or intracellular antigens. Some cases are known to be associated with anti-channel or anti-receptor-related molecule antibodies. Whether these cases are paraneoplastic depends on the kinds of antigens that the antibodies are produced against. Other cases due to well-characterized onco-neural antibodies are almost always paraneoplastic and are generally resistant to anti-tumor therapy and/or immunotherapy. An exception is anti-Ma2 antibody-positive encephalitis associated with a testicular tumor. Antibodies for intracellular antigens are considered not to be pathogenic. Rather, the T-cell response is thought to be responsible. These antibodies are useful markers for the diagnosis of paraneoplastic disorders and in the search for underlying cancer, as neurological symptoms often precede tumor diagnosis. There is a relationship among onco-neural antibodies, clinical features, tumor types, and response to immunotherapy. Here we describe the characteristics of autoimmune encephalitis cases with antibodies against different intracellular antigens, such as Hu, Ma2, CRMP5, or amphiphysin.

  17. Endocrine autoimmune diseases and female infertility. (United States)

    Sen, Aritro; Kushnir, Vitaly A; Barad, David H; Gleicher, Norbert


    An increasing body of evidence suggests that immune-mediated processes affect female reproductive success at multiple levels. Crosstalk between endocrine and immune systems regulates a large number of biological processes that affect target tissues, and this crosstalk involves gene expression, cytokine and/or lymphokine release and hormone action. In addition, endocrine-immune interactions have a major role in the implantation process of the fetal (paternally derived) semi-allograft, which requires a reprogramming process of the maternal immune system from rejection to temporary tolerance for the length of gestation. Usually, the female immune system is supportive of all of these processes and, therefore, facilitates reproductive success. Abnormalities of the female immune system, including autoimmunity, potentially interfere at multiple levels. The relevance of the immune system to female infertility is increasingly recognized by investigators, but clinically is often not adequately considered and is, therefore, underestimated. This Review summarizes the effect of individual autoimmune endocrine diseases on female fertility, and points towards selected developments expected in the near future.

  18. Autoimmune pancreatitis can develop into chronic pancreatitis. (United States)

    Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Kawa, Shigeyuki


    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct.

  19. Antibodies to actin in autoimmune haemolytic anaemia

    Directory of Open Access Journals (Sweden)

    Ritzmann Mathias


    Full Text Available Abstract Background In autoimmune haemolytic anaemia (AIHA, autoreactive antibodies directed against red blood cells are up-regulated, leading to erythrocyte death. Mycoplasma suis infections in pigs induce AIHA of both the warm and cold types. The aim of this study was to identify the target autoantigens of warm autoreactive IgG antibodies. Sera from experimentally M. suis-infected pigs were screened for autoreactivity. Results Actin-reactive antibodies were found in the sera of 95% of all animals tested. The reactivity was species-specific, i.e. reactivity with porcine actin was significantly higher than with rabbit actin. Sera of animals previously immunised with the M. suis adhesion protein MSG1 showed reactivity with actin prior to infection with M. suis indicating that molecular mimicry is involved in the specific autoreactive mechanism. A potentially cross-reactive epitope was detected. Conclusions This is the first report of autoreactive anti-actin antibodies involved in the pathogenesis of autoimmune haemolytic anaemia.

  20. Vitamin D in the Spectrum of Prediabetes and Cardiovascular Autonomic Dysfunction. (United States)

    Dimova, Rumyana; Tankova, Tsvetalina; Chakarova, Nevena


    Vitamin D is a fat-soluble secosteroid hormone with pleiotropic effects. 1,25-Dihydroxyvitamin D coordinates the biosynthesis of neurotransmitters in the central nervous system, which regulate cardiovascular autonomic function and may explain its putative role in the development of cardiovascular autonomic neuropathy (CAN). CAN is an independent risk factor for mortality in patients with diabetes and prediabetes and is associated with an increased risk of developing type 2 diabetes and cardiovascular disease. Accumulating data indicate the presence of peripheral nerve injury at these early stages of dysglycemia and its multifactorial pathogenesis. Prediabetes is associated with vitamin D insufficiency. Vitamin D is proposed to prevent the progression of glucose intolerance. The putative underlying mechanisms include maintenance of the intracellular calcium concentration, direct stimulation of insulin receptor expression, and enhancement of the insulin response to glucose transporters. Vitamin D exerts a protective effect on peripheral nerve fibers by decreasing the demyelination process and inducing axonal regeneration. The effects of vitamin D supplementation on glucose tolerance and related autonomic nerve dysfunction have been a recent focus of scientific interest. Although well-designed observational studies are available, the causative relation between vitamin D deficiency, glucose intolerance, and CAN is still debatable. One reason might be that interventional studies are unpersuasive with regard to the beneficial clinical effects of vitamin D supplementation. Because of its favorable side effect profile, vitamin D supplementation might represent an attractive therapeutic option for treating the pandemic prevalence of prediabetes and vitamin D deficiency. Vitamin D supplementation can improve glucose tolerance and cardiovascular autonomic function and can thus reduce cardiovascular mortality among subjects with different stages of glucose intolerance and

  1. Clinical implications of shared genetics and pathogenesis in autoimmune diseases

    NARCIS (Netherlands)

    Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca


    Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the

  2. AIRE variations in Addison's disease and autoimmune polyendocrine syndromes (APS)

    DEFF Research Database (Denmark)

    Bøe Wolff, A S; Oftedal, B; Johansson, S


    Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms...

  3. Moving towards a molecular taxonomy of autoimmune rheumatic diseases

    NARCIS (Netherlands)

    Barturen, Guillermo; Beretta, Lorenzo; Cervera, Ricard; van Vollenhoven, Ronald; Alarcón-Riquelme, Marta E.


    Autoimmune rheumatic diseases pose many problems that have, in general, already been solved in the field of cancer. The heterogeneity of each disease, the clinical similarities and differences between different autoimmune rheumatic diseases and the large number of patients that remain without a

  4. Autoimmune progesterone dermatitis: Case report with history of ...

    African Journals Online (AJOL)

    Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when ...

  5. Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

    NARCIS (Netherlands)

    de Jager, AEJ; van der Hoeven, JH

    Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually

  6. Selected Aspects in the Pathogenesis of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    György Nagy


    Full Text Available Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.

  7. Autoimmune disease in children and adolescents with psoriasis

    DEFF Research Database (Denmark)

    Blegvad, Christoffer; Egeberg, Alexander; Tind Nielsen, Tilde E.


    arthritis (adjusted OR 6.61; 2.75–15.87) and vitiligo (adjusted OR 4.76; 1.71–13.20) showed strong associations with psoriasis. In addition to increased risk of selected autoimmune diseases, the presence of psoriasis was associated with increased risk of multiple concurrent autoimmune diseases compared...


    Saidova, F Kh; Shakhsuvarov, O M; Guseynov, R G; Akhmedova, L M; Aslanova, Zh B


    A state of autoimmunity was studied in 25 patients, suffering diffuse toxic goiter (DTG), and in 20--in nodular euthyroid goiter (NEG) before and after the operation. The level of circulating immune complexes, quantity of cytotoxic lymphocytes, the subpopulation index, the apoptosis marker were determined. There was established, that in NEG autoimmune disorders have occurred rarer and were less severe, than in DTG.

  9. Autoimmune polyglandular syndrome in a 13-year old girl

    DEFF Research Database (Denmark)

    Borgwardt, L.; Pedersen, P.; Peitersen, B.


    Autoimmune polyglandular syndrome (APS) is an entity, defined by autoimmunity towards two or more endocrine organs. APS is classified in 3 subgroups (type-1, type-2a, type-2b), according to the organs involved. A case is presented of a 13-year old girl referred to the Department of Paediatrics...

  10. Cellular immunity and immunopathology in autoimmune Addison's disease. (United States)

    Bratland, Eirik; Husebye, Eystein S


    Autoimmune adrenocortical failure, or Addison's disease, is a prototypical organ-specific autoimmune disorder. In common with related autoimmune endocrinopathies, Addison's disease is only manageable to a certain extent with replacement therapy being the only treatment option. Unfortunately, the available therapy does not restore the physiological hormone levels and biorhythm. The key to progress in treating and preventing autoimmune Addison's disease lies in improving our understanding of the predisposing factors, the mechanisms responsible for the progression of the disease, and the interactions between adrenal antigens and effector cells and molecules of the immune system. The aim of the present review is to summarize the current knowledge on the role of T cells and cellular immunity in the pathogenesis of autoimmune Addison's disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity

    Directory of Open Access Journals (Sweden)

    Lauren M.F. Merlo


    Full Text Available Indoleamine 2,3-dioxygenase 2 (IDO2, a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1. IDO2 is expressed in antigen-presenting cells, including B cells and dendritic cells, but affects inflammatory responses in the autoimmune context specifically by acting in B cells to modulate T cell help in multiple model systems. Given that expression of IDO2 can lead to exacerbation of inflammatory responses, IDO2 should be considered a potential therapeutic target for autoimmune disorders.

  12. The prevalence of autoimmune disease in patients with esophageal achalasia. (United States)

    Booy, J D; Takata, J; Tomlinson, G; Urbach, D R


    Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10-15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5-19), 8.5 times as likely to have hypothyroidism (95% CI 5.0-14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9-205), 43 times as likely to have systemic lupus erythematosus (95% CI 12-154), and 259 times as likely to have uveitis (95% CI 13-1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5-5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  13. Autonomous Cryogenics Loading Operations Simulation Software: Knowledgebase Autonomous Test Engineer (United States)

    Wehner, Walter S., Jr.


    Working on the ACLO (Autonomous Cryogenics Loading Operations) project I have had the opportunity to add functionality to the physics simulation software known as KATE (Knowledgebase Autonomous Test Engineer), create a new application allowing WYSIWYG (what-you-see-is-what-you-get) creation of KATE schematic files and begin a preliminary design and implementation of a new subsystem that will provide vision services on the IHM (Integrated Health Management) bus. The functionality I added to KATE over the past few months includes a dynamic visual representation of the fluid height in a pipe based on number of gallons of fluid in the pipe and implementing the IHM bus connection within KATE. I also fixed a broken feature in the system called the Browser Display, implemented many bug fixes and made changes to the GUI (Graphical User Interface).

  14. Enteroviruses and type 1 diabetes mellitus putative pathogenic pathways

    NARCIS (Netherlands)

    Vreugdenhil, Gienke Rolien


    Type I diabetes mellitus is a chronic autoimmune disease that results from the destruction of the insulin-producing beta-cells in the endocrine pancreas. There is strong evidence that besides genetic factors, environmental factors are involved in the pathogenesis of the disease. Increasing

  15. Autonomic computing enabled cooperative networked design

    CERN Document Server

    Wodczak, Michal


    This book introduces the concept of autonomic computing driven cooperative networked system design from an architectural perspective. As such it leverages and capitalises on the relevant advancements in both the realms of autonomic computing and networking by welding them closely together. In particular, a multi-faceted Autonomic Cooperative System Architectural Model is defined which incorporates the notion of Autonomic Cooperative Behaviour being orchestrated by the Autonomic Cooperative Networking Protocol of a cross-layer nature. The overall proposed solution not only advocates for the inc

  16. The use of rhG-CSF in chronic autoimmune neutropenia: reversal of autoimmune phenomena, a case history

    NARCIS (Netherlands)

    Kuijpers, T. W.; de Haas, M.; de Groot, C. J.; von dem Borne, A. E.; Weening, R. S.


    An 8-year-old boy had been suffering from chronic autoimmune neutropenia for more than 5 years. The neutropenia proved to be resistant to high-dose steroids and intravenous (either low-or high-dose) immunoglobulin (Ig) therapy. The chronic autoimmune thrombocytopenia and recurrent phases of

  17. A rare combination of type 3 autoimmune polyendocrine syndrome (APS-3) or multiple autoimmune syndrome (MAS-3). (United States)

    Betterle, Corrado; Garelli, Silvia; Coco, Graziella; Burra, Patrizia


    Type 3 autoimmune polyendocrine syndrome (APS-3) is defined by the presence of an autoimmune thyroid disease and another autoimmune illness, excluding Addison's disease; this is a frequent combination. We report the case of a 55 years old female patient with APS-3, with seven clinical or latent autoimmune manifestations. At 49 years of age she was admitted at the General Hospital for leukopenia, weight loss, tremors, anxiety and diarrhea. The personal history revealed ulcerative colitis and, during the last year, episodes of fever with migrant arthralgia and cutaneous lesions. The patient was evaluated for thyroid function and imaging, mielobiopsy, glycaemic control, gastrointestinal and rheumatologic disorders with specific biochemical tests, imaging and endoscopic procedures. We concluded that the patient was affected by APS-3, characterized by the association of Graves' disease, autoimmune leukopenia, latent autoimmune diabetes of the adult (LADA), autoimmune gastritis, ulcerative colitis, Sjögren's and anti-phospholipid syndromes. The patient started low doses of corticosteroid drugs for leukopenia, underwent (131)I therapy for hyperthyroidism and later started substitutive thyroid therapy with l-thyroxine, insulin therapy for LADA, mesalazine for ulcerative colitis and artificial tears for Sjögren's syndrome. In this article we report a complex case of APS-3, characterized by the association of seven different autoimmune diseases, which required a complex therapeutic strategy.

  18. Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome. (United States)

    Mitsumoto, H; Schwartzman, M J; Estes, M L; Chou, S M; La Franchise, E F; De Camilli, P; Solimena, M


    Two women with typical stiff-man syndrome (SMS) developed increasingly frequent attacks of muscle spasms with severe paroxysmal autonomic dysfunctions such as transient hyperpyrexia, diaphoresis, tachypnea, tachycardia, pupillary dilation, and arterial hypertension. Autoantibodies to GABA-ergic neurons were identified in the serum of both patients and in the cerebrospinal fluid of one. Both died suddenly and unexpectedly. General autopsy did not reveal the cause of death. Neuropathological studies revealed perivascular gliosis in the spinal cord and brain stem of one patient and lymphocytic perivascular infiltration in the spinal cord, brain stem, and basal ganglia of the other. The occurrence of a chronic inflammatory reaction in one of the two patients supports the idea that an autoimmune disease against GABA-ergic neurons may be involved in SMS. A review of the literature indicates that functional impairment in SMS is severe and prognosis is unpredictable because of the potential for sudden and unexpected death. Both muscular abnormalities and autonomic dysfunctions may result from autoimmunity directed against GABA-ergic neurons.

  19. Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

    Directory of Open Access Journals (Sweden)

    Heung Yong Jin


    Full Text Available Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM and type 2 diabetes mellitus (T2DM. Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN. Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed.

  20. Insights into the background of autonomic medicine. (United States)

    Laranjo, Sérgio; Geraldes, Vera; Oliveira, Mário; Rocha, Isabel


    Knowledge of the physiology underlying the autonomic nervous system is pivotal for understanding autonomic dysfunction in clinical practice. Autonomic dysfunction may result from primary modifications of the autonomic nervous system or be secondary to a wide range of diseases that cause severe morbidity and mortality. Together with a detailed history and physical examination, laboratory assessment of autonomic function is essential for the analysis of various clinical conditions and the establishment of effective, personalized and precise therapeutic schemes. This review summarizes the main aspects of autonomic medicine that constitute the background of cardiovascular autonomic dysfunction. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. TREX1 deficiency triggers cell-autonomous immunity in a cGAS-dependent manner. (United States)

    Ablasser, Andrea; Hemmerling, Inga; Schmid-Burgk, Jonathan L; Behrendt, Rayk; Roers, Axel; Hornung, Veit


    Cytosolic detection of DNA is crucial for the initiation of antiviral immunity but can also cause autoimmunity in the context of endogenous nucleic acids being sensed. Mutations in the human 3' repair exonuclease 1 (TREX1) have been linked to the type I IFN-associated autoimmune disease Aicardi-Goutières syndrome. The exact mechanisms driving unabated type I IFN responses in the absence of TREX1 are only partly understood, but it appears likely that accumulation of endogenous DNA species triggers a cell-autonomous immune response by activating a cytosolic DNA receptor. In this article, we demonstrate that knocking out the DNA sensor cyclic GMP-AMP synthase completely abrogates spontaneous induction of IFN-stimulated genes in TREX1-deficient cells. These findings indicate a key role of cyclic GMP-AMP synthase for the initiation of self-DNA-induced autoimmune disorders, thus providing important implications for novel therapeutic approaches. Copyright © 2014 by The American Association of Immunologists, Inc.

  2. Transplantation of autoimmune potential. IV. Reversal of the NZB autoimmune syndrome by bone marrow transplantation

    International Nuclear Information System (INIS)

    Morton, J.I.; Siegel, B.V.


    The results of the present experiments support the concept of an etiology of autoimmune disease predicated upon innate properties of the hemopoietic stem cell and its differentiated lymphocytic progeny, independent of the host internal environment. It was concluded earlier that the NZB mouse strain possessed an enlarged compartment of cyclically active stem cells, providing an etiological basis for the development of autoimmune disease. Conceivably, a rapidly cycling stem cell population could randomly generate excessive numbers of lymphocytic progeny. Autoantibody formation would represent, then, a manifestation of the consequent hyperresponsiveness to immunological stimuli, both foreign and autologous. Alternatively, there may exist a parallel defect in the homeostatic regulation of both stem cell and immunocyte populations, attributable to either a defect in a shared regulator mechanism or to an unusually high threshold of these cells in response to negative feedback signals

  3. Goodpasture's autoimmune disease - A collagen IV disorder. (United States)

    Pedchenko, Vadim; Richard Kitching, A; Hudson, Billy G


    Goodpasture's (GP) disease is an autoimmune disorder characterized by the deposition of pathogenic autoantibodies in basement membranes of kidney and lung eliciting rapidly progressive glomerulonephritis and pulmonary hemorrhage. The principal autoantigen is the α345 network of collagen IV, which expression is restricted to target tissues. Recent discoveries include a key role of chloride and bromide for network assembly, a novel posttranslational modification of the antigen, a sulfilimine bond that crosslinks the antigen, and the mechanistic role of HLA in genetic susceptibility and resistance to GP disease. These advances provide further insights into molecular mechanisms of initiation and progression of GP disease and serve as a basis for developing of novel diagnostic tools and therapies for treatment of Goodpasture's disease. Copyright © 2017. Published by Elsevier B.V.

  4. Pharmacometabolomics-aided Pharmacogenomics in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Theodora Katsila


    Full Text Available Inter-individual variability has been a major hurdle to optimize disease management. Precision medicine holds promise for improving health and healthcare via tailor-made therapeutic strategies. Herein, we outline the paradigm of “pharmacometabolomics-aided pharmacogenomics” in autoimmune diseases. We envisage merging pharmacometabolomic and pharmacogenomic data (to address the interplay of genomic and environmental influences with information technologies to facilitate data analysis as well as sense- and decision-making on the basis of synergy between artificial and human intelligence. Humans can detect patterns, which computer algorithms may fail to do so, whereas data-intensive and cognitively complex settings and processes limit human ability. We propose that better-informed, rapid and cost-effective omics studies need the implementation of holistic and multidisciplinary approaches.

  5. Dry Eye as a Mucosal Autoimmune Disease (United States)

    Stern, Michael E.; Schaumburg, Chris S.; Pflugfelder, Stephen C.


    Dry eye is a common ocular surface inflammatory disease that significantly affects quality of life. Dysfunction of the lacrimal function unit (LFU) alters tear composition and breaks ocular surface homeostasis, facilitating chronic inflammation and tissue damage. Accordingly, the most effective treatments to date are geared towards reducing inflammation and restoring normal tear film. The pathogenic role of CD4+ T cells is well known, and the field is rapidly realizing the complexity of other innate and adaptive immune factors involved in the development and progression of disease. The data support the hypothesis that dry eye is a localized autoimmune disease originating from an imbalance in the protective immunoregulatory and proinflammatory pathways of the ocular surface. PMID:23360156

  6. Statin-induced autoimmune necrotizing myositis

    Directory of Open Access Journals (Sweden)

    Katarzyna Ząber


    Full Text Available Myositides comprise a large group of disorders involving limb muscle weakness. In differential diagnosis we have to consider idiopathic myositides, myositides associated with other diseases, and those induced by external factors, e.g. drug-induced. Statins are commonly used drugs, but many patients experience a broad spectrum of adverse effects including symptoms from skeletal muscle. Physicians should pay special attention to patients reporting muscle weakness lasting longer than 12 weeks, despite statin withdrawal, as well as other symptoms: dysphagia, disturbed grip function, elevated creatinine kinase (CK levels and abnormal electromyography. The reported case deals with the problem of differential diagnosis of drug-induced muscle injury, polymyositis with a recently reported myopathy – statin-induced autoimmune necrotizing myositis, related to anti-HMGCR antibodies.

  7. Autoimmune Thyroiditis Presenting as Palmoplantar Keratoderma

    Directory of Open Access Journals (Sweden)

    Sara Lestre


    Full Text Available Palmoplantar keratoderma is a heterogeneous group of hereditary and acquired disorders characterized by abnormal thickening of palms and soles. Hypothyroidism is an unusual cause of palmoplantar keratoderma, rarely reported in the literature. We report a case of a 43-year-old woman presented with a 3-month history of a diffuse palmoplantar hyperkeratosis unresponsive to topical keratolytics and corticosteroids. Her past medical and family histories were unremarkable. She complained of recent asthenia, mood changes and constipation. Laboratory evaluation revealed an autoimmune thyroiditis with hypothyroidism. Other causes of acquired palmoplantar keratoderma were excluded. After hormonal replacement therapy institution, a gradual improvement of skin condition was observed. The diagnosis of underlying causes for acquired palmoplantar keratoderma can be a difficult task; however its recognition is essential for successful treatment results. Although a very rare association, hypothyroidism must be suspected in patients with acquired palmoplantar keratoderma, particularly when it occurs in association with systemic symptoms.

  8. Cardiovascular autonomic neuropathy in diabetes

    DEFF Research Database (Denmark)

    Spallone, Vincenza; Ziegler, Dan; Freeman, Roy


    Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control...... in type 2 diabetes. CAN is a risk marker of mortality and cardiovascular morbidity, and possibly a progression promoter of diabetic nephropathy. Criteria for CAN diagnosis and staging are: 1. one abnormal cardio-vagal test identifies possible or early CAN; 2. at least two abnormal cardio-vagal tests....... diagnosis of CAN clinical forms, 2. detection and tailored treatment of CAN clinical correlates (e.g. tachycardia, OH, nondipping, QT interval prolongation), 3. risk stratification for diabetic complications and cardiovascular morbidity and mortality, and 4. modulation of targets of diabetes therapy...

  9. Autonomous Laser-Powered Vehicle (United States)

    Stone, William C. (Inventor); Hogan, Bartholomew P. (Inventor)


    An autonomous laser-powered vehicle designed to autonomously penetrate through ice caps of substantial (e.g., kilometers) thickness by melting a path ahead of the vehicle as it descends. A high powered laser beam is transmitted to the vehicle via an onboard bare fiber spooler. After the beam enters through the dispersion optics, the beam expands into a cavity. A radiation shield limits backscatter radiation from heating the optics. The expanded beam enters the heat exchanger and is reflected by a dispersion mirror. Forward-facing beveled circular grooves absorb the reflected radiant energy preventing the energy from being reflected back towards the optics. Microchannels along the inner circumference of the beam dump heat exchanger maximize heat transfer. Sufficient amount of fiber is wound on the fiber spooler to permit not only a descent but also to permit a sample return mission by inverting the vehicle and melting its way back to the surface.

  10. Health, autonomic financing and transferences

    Directory of Open Access Journals (Sweden)

    David Cantarero Prieto


    Full Text Available The present paper has as objective to study the whole relative problem to the autonomous communities and regional heath care expenditure financing in Spain. This article has a dual purpose. First, the financing of the current health care attendance is approached in the Spanish regions passing magazine to its possible variants and we observe that the balance of our system is clearly inclined towards the side of the integration in the general pattern of financing («Fiscal Room» with specific conditions («Mixed System». Secondly, we examine the new situation in the mark of health care and its corresponding financing in the new model approved in 2001, in terms of the effects of tax assignment on autonomous communities.

  11. Autonomously managed high power systems

    International Nuclear Information System (INIS)

    Weeks, D.J.; Bechtel, R.T.


    The need for autonomous power management capabilities will increase as the power levels of spacecraft increase into the multi-100 kW range. The quantity of labor intensive ground and crew support consumed by the 9 kW Skylab cannot be afforded in support of a 75-300 kW Space Station or high power earth orbital and interplanetary spacecraft. Marshall Space Flight Center is managing a program to develop necessary technologies for high power system autonomous management. To date a reference electrical power system and automation approaches have been defined. A test facility for evaluation and verification of management algorithms and hardware has been designed with the first of the three power channel capability nearing completion

  12. Development of autonomous operation system

    International Nuclear Information System (INIS)

    Endou, Akira; Watanabe, Kenshiu; Miki, Tetsushi


    To enhance operation reliability of nuclear plants by removing human factors, study on an autonomous operation system has been carried out to substitute artificial intelligence (AI) for plant operators and, in addition, traditional controllers used in existing plants. For construction of the AI system, structurization of knowledge on the basis of the principles such as physical laws, function and structure of relevant objects and generalization of problem solving process are intended. A hierarchical distributed cooperative system configuration in employed because it is superior from the viewpoint of dynamical reorganization of system functions. This configuration is realized by an object-oriented multi-agent system. Construction of a prototype system was planned and the conceptual design was made for FBR plant in order to evaluate applicability of AI to the autonomous operation and to have a prospect for the realization of the system. The prototype system executes diagnosis, state evaluation, operation and control for the main plant subsystems. (author)

  13. Autonomous Agents as Artistic Collaborators

    DEFF Research Database (Denmark)

    Kadish, David

    In this paper, I ask whether it is possible to exert creative direction on the emergence of large scale patterns from the actions of autonomous or semi-autonomous actors. As an artist and an engineer, I undertake installations and projects with an intent to create, to make art or innovative...... structures. At the same time, one of my artistic interests is in ceding a great deal of creative control to a cluster of robotic actors, in the process interrogating the lack of control that we, as a species, exert over the world. Here, I explore this idea in the context of an ongoing project called...... that navigate the space as well. My work has implications for how we as a species address planetary-scale challenges and whether we can organize societies to find emergent solutions to complex problems. Behind my artistic interest is the idea that "creation" has no teleological impulse. The creative force from...

  14. Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity. (United States)

    Cascio, Michael J; Jen, Kuang-Yu


    Levamisole was previously used for its immunomodulatory properties to treat rheumatoid arthritis and some cancers. However, because of serious side-effects, it was taken off the market in the United States. Recently, levamisole has reemerged as a popular cocaine adulterant. Some individuals who consume levamisole-adulterated cocaine can develop a life-threatening autoimmune syndrome. In this review, the medical consequences of levamisole exposure and postulated mechanisms by which levamisole induces these adverse effects are discussed. Although agranulocytosis and cutaneous vasculitis are the major findings in patients who develop cocaine/levamisole-associated autoimmune syndrome (CLAAS), more recent experience indicates that other organ systems can be involved as well. Current studies point to neutrophil activation and neutrophil extracellular trap formation with subsequent antineutrophil cytoplasmic antibody-mediated tissue injury as a possible mechanism of CLAAS. In the past decade, the detrimental effects of levamisole have reemerged because of its popularity as a cocaine adulterant. Although infrequent, some individuals develop a systemic autoimmune syndrome characterized by immune-mediated agranulocytosis and antineutrophil cytoplasmic antibody-mediated vasculitis. Mechanistically, neutrophil antigens appear to be a major player in inducing CLAAS. Prompt cessation of levamisole exposure is key to treatment, although relapses are frequent because of the addictive effects of cocaine and the high prevalence of levamisole within the cocaine supply.

  15. Autonomous spacecraft rendezvous and docking (United States)

    Tietz, J. C.; Almand, B. J.

    A storyboard display is presented which summarizes work done recently in design and simulation of autonomous video rendezvous and docking systems for spacecraft. This display includes: photographs of the simulation hardware, plots of chase vehicle trajectories from simulations, pictures of the docking aid including image processing interpretations, and drawings of the control system strategy. Viewgraph-style sheets on the display bulletin board summarize the simulation objectives, benefits, special considerations, approach, and results.

  16. Biology-Inspired Autonomous Control (United States)


    insect brain, allow these animals to fly with damaged wings, order of body mass payloads (e.g., foraging bees with a load of pollen , blood satiated...The research focus addressed two broad, complementary research areas : autonomous systems concepts inspired by the behavior and neurobiology...UL 46 19b. TELEPHONE NUMBER (include area code) 850 883-1887 Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 iii Table of

  17. Autonomous Electrical Vehicles’ Charging Station


    Józef Paska; Mariusz Kłos; Łukasz Rosłaniec; Rafał Bielas; Magdalena Błędzińska


    This paper presents a model of an autonomous electrical vehicles’ charging station. It consists of renewable energy sources: wind turbine system, photovoltaic cells, as well as an energy storage, load, and EV charging station. In order to optimise the operating conditions, power electronic converters were added to the system. The model was implemented in the Homer Energy programme. The first part of the paper presents the design assumptions and technological solutions. Further in the paper...

  18. Fleet management for autonomous vehicles


    Bsaybes, Sahar; Quilliot, Alain; Wagler, Annegret K.


    The VIPAFLEET project consists in developing models and algorithms for man- aging a fleet of Individual Public Autonomous Vehicles (VIPA). Hereby, we consider a fleet of cars distributed at specified stations in an industrial area to supply internal transportation, where the cars can be used in different modes of circulation (tram mode, elevator mode, taxi mode). One goal is to develop and implement suitable algorithms for each mode in order to satisfy all the requests under an economic point...

  19. Urban planning for autonomous vehicles


    Fourie, Pieter J.; Ordoñez Medina, Sergio A.; Maheshwari, Tanvi; Wang, Biyu; Erath, Alexander; Cairns, Stephen; Axhausen, Kay W.


    In land-scarce Singapore, population growth and increasingly dense development are running up against limited remaining space for mobility infrastructure expansion. Autonomous Vehicles (AV) promise to relieve some of this pressure, through more efficient use of road space through platooning and intersection coordination, reducing the need for parking space, and reducing overall reliance on privately owned cars, realising Singapore’s vision of a “car-lite” future. In a collaborative resear...

  20. Failure Prediction for Autonomous Driving


    Hecker, Simon; Dai, Dengxin; Van Gool, Luc


    The primary focus of autonomous driving research is to improve driving accuracy. While great progress has been made, state-of-the-art algorithms still fail at times. Such failures may have catastrophic consequences. It therefore is important that automated cars foresee problems ahead as early as possible. This is also of paramount importance if the driver will be asked to take over. We conjecture that failures do not occur randomly. For instance, driving models may fail more likely at places ...

  1. Autonomic computing meets SCADA security


    Nazir, S; Patel, S; Patel, D


    © 2017 IEEE. National assets such as transportation networks, large manufacturing, business and health facilities, power generation, and distribution networks are critical infrastructures. The cyber threats to these infrastructures have increasingly become more sophisticated, extensive and numerous. Cyber security conventional measures have proved useful in the past but increasing sophistication of attacks dictates the need for newer measures. The autonomic computing paradigm mimics the auton...

  2. Autonomic neuropathy in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Alberto eVerrotti


    Full Text Available Diabetic autonomic neuropathy (DAN is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy (CAN defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. The pathogenesis is still unclear and probably multifactorial. Once DAN becomes clinically evident, no form of therapy has been identified which can effectively stop or reverse it. Prevention strategies are based on strict glycemic control with intensive insulin treatment, multifactorial intervention and lifestyle modification including control of hypertension, dyslipidemia, stop smoking, weight loss and adequate physical exercise. The present review summarizes the latest knowledge regarding clinical presentation, epidemiology, pathogenesis and management of DAN, with some mention to childhood and adolescent population.

  3. Oxidative and nitrosative stress in trichloroethene-mediated autoimmune response

    International Nuclear Information System (INIS)

    Wang Gangduo; Cai Ping; Ansari, G.A.S.; Khan, M. Firoze


    Reactive oxygen and nitrogen species (RONS) are implicated in the pathogenesis of several autoimmune diseases. Also, increased lipid peroxidation and protein nitration are reported in systemic autoimmune diseases. Lipid peroxidation-derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are highly reactive and bind proteins covalently, but their potential to elicit an autoimmune response and contribution to disease pathogenesis remain unclear. Similarly, nitration of protein could also contribute to disease pathogenesis. To assess the status of lipid peroxidation and/or RONS, autoimmune-prone female MRL+/+ mice (5-week old) were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 48 weeks (0.5 mg/ml via drinking water), and formation of antibodies to LPDA-protein adducts was followed in the sera of control and TCE-treated mice. TCE treatment led to greater formation of both anti-MDA- and -HNE-protein adduct antibodies and higher serum iNOS and nitrotyrosine levels. The increase in TCE-induced oxidative stress was associated with increases in anti-nuclear-, anti-ssDNA- and anti-dsDNA-antibodies. These findings suggest that TCE exposure not only leads to oxidative/nitrosative stress, but is also associated with induction/exacerbation of autoimmune response in MRL+/+ mice. Further interventional studies are needed to establish a causal role of RONS in TCE-mediated autoimmunity

  4. Predicting post-vaccination autoimmunity: who might be at risk? (United States)

    Soriano, Alessandra; Nesher, Gideon; Shoenfeld, Yehuda


    Vaccinations have been used as an essential tool in the fight against infectious diseases, and succeeded in improving public health. However, adverse effects, including autoimmune conditions may occur following vaccinations (autoimmune/inflammatory syndrome induced by adjuvants--ASIA syndrome). It has been postulated that autoimmunity could be triggered or enhanced by the vaccine immunogen contents, as well as by adjuvants, which are used to increase the immune reaction to the immunogen. Fortunately, vaccination-related ASIA is uncommon. Yet, by defining individuals at risk we may further limit the number of individuals developing post-vaccination ASIA. In this perspective we defined four groups of individuals who might be susceptible to develop vaccination-induced ASIA: patients with prior post-vaccination autoimmune phenomena, patients with a medical history of autoimmunity, patients with a history of allergic reactions, and individuals who are prone to develop autoimmunity (having a family history of autoimmune diseases; asymptomatic carriers of autoantibodies; carrying certain genetic profiles, etc.). Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. [Oral diseases in auto-immune polyendocrine syndrome type 1]. (United States)

    Proust-Lemoine, Emmanuelle; Guyot, Sylvie


    Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. High salt intake does not exacerbate murine autoimmune thyroiditis (United States)

    Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G


    Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002

  7. Polyglandular Autoimmune Syndrome Type III with Primary Hypoparathyroidism

    Directory of Open Access Journals (Sweden)

    Sang Jin Kim


    Full Text Available Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day for 11 years. She had insulin deficiency and Hashimoto thyroiditis as an autoimmune disorder. In addition, she had several features similar to Albright's hereditary osteodystrophy including short stature, truncal obesity, round face, short neck, low intelligence (full IQ 84, and decreased memory. Although Albright's hereditary osteodystrophy is morphological evidence of pseudohypoparathyroidism or pseudopseudohypoparathyroidism, she had primary hypoparathyroidism on laboratory results. Here, we report a case of polyglandular autoimmune syndrome III with type 1 diabetes mellitus, autoimmune thyroiditis, and primary hypoparathyroidism, accompanied by clinical features similar to Albright's hereditary osteodystrophy.


    Adams Waldorf, Kristina M.; Nelson, J. Lee


    Pregnancy has both short-term effects and long-term consequences. For women who have an autoimmune disease and subsequently become pregnant, pregnancy can induce amelioration of the mother’s disease, such as in rheumatoid arthritis, while exacerbating or having no effect on other autoimmune diseases like systemic lupus erythematosus. That pregnancy also leaves a long-term legacy has recently become apparent by the discovery that bi-directional cell trafficking results in persistence of fetal cells in the mother and of maternal cells in her offspring for decades after birth. The long-term persistence of a small number of cells (or DNA) from a genetically disparate individual is referred to as microchimerism. While microchimerism is common in healthy individuals and is likely to have health benefits, microchimerism has been implicated in some autoimmune diseases such as systemic sclerosis. In this paper, we will first discuss short-term effects of pregnancy on women with autoimmune disease. Pregnancy-associated changes will be reviewed for selected autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. The pregnancy-induced amelioration of rheumatoid arthritis presents a window of opportunity for insights into both immunological mechanisms of fetal-maternal tolerance and pathogenic mechanisms in autoimmunity. A mechanistic hypothesis for the pregnancy-induced amelioration of rheumatoid arthritis will be described. We will then discuss the legacy of maternal-fetal cell transfer from the perspective of autoimmune diseases. Fetal and maternal microchimerism will be reviewed with a focus on systemic sclerosis (scleroderma), autoimmune thyroid disease, neonatal lupus and type I diabetes mellitus. PMID:18716941

  9. A putative hybrid swarm within Oonopsis foliosa (Asteraceae: Astereae) (United States)

    Hughes, J.F.; Brown, G.K.


    Oo??nopsis foliosa var. foliosa and var. monocephala are endemic to short-grass steppe of southeastern Colorado and until recently were considered geographically disjunct. The only known qualitative feature separating these 2 varieties is floral head type; var. foliosa has radiate heads, whereas var. monocephala heads are discoid. Sympatry between these varieties is restricted to a small area in which a range of parental types and intermediate head morphologies is observed. We used distribution mapping, morphometric analyses, chromosome cytology, and pollen stainability to characterize the sympatric zone. Morphometrics confirms that the only discrete difference between var. foliosa and var. monocephala is radiate versus discoid heads, respectively. The outer florets of putative hybrid individuals ranged from conspicuously elongated yet radially symmetric disc-floret corollas, to elongated radially asymmetric bilabiate- or deeply cleft corollas, to stunted ray florets with appendages remnant of corolla lobes. Chromosome cytology of pollen mother cells from both putative parental varieties and a series of intermediate morphological types collected at the sympatric zone reveal evidence of translocation heterozygosity. Pollen stainability shows no significant differences in viability between the parental varieties and putative hybrids. The restricted distribution of putative hybrids to a narrow zone of sympatry between the parental types and the presence of meiotic chromosome-pairing anomalies in these intermediate plants are consistent with a hybrid origin. The high stainability of putative-hybrid pollen adds to a growing body of evidence that hybrids are not universally unfit.

  10. Autoimmune pancreatitis in an 11-year-old boy

    International Nuclear Information System (INIS)

    Refaat, Rania; Harth, Marc; Proschek, Petra; Lindemayr, Sebastian; Vogl, Thomas J.


    We report a case of histopathologically proven autoimmune pancreatitis in an 11-year-old boy. Abdominal US and MRI showed a focal swelling of the pancreatic head, the latter also showing delayed contrast enhancement. There was diffuse irregular pancreatic duct narrowing, compression of the intrapancreatic common bile duct, and mild proximal biliary dilatation on MR cholangiopancreatography. Laboratory results revealed normal serum IgG and subclass 4 with negative autoimmune antibodies, and slightly elevated carbohydrate antigen 19-9. This highlights the differentiation of autoimmune pancreatitis from pancreatic head cancer and, to a lesser extent, other forms of pancreatitis in children. (orig.)

  11. Autoimmune pancreatitis in an 11-year-old boy

    Energy Technology Data Exchange (ETDEWEB)

    Refaat, Rania [Johann-Wolfgang-Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany); Ain Shams University, Department of Diagnostic and Interventional Radiology, Cairo (Egypt); Harth, Marc; Proschek, Petra; Lindemayr, Sebastian; Vogl, Thomas J. [Johann-Wolfgang-Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany)


    We report a case of histopathologically proven autoimmune pancreatitis in an 11-year-old boy. Abdominal US and MRI showed a focal swelling of the pancreatic head, the latter also showing delayed contrast enhancement. There was diffuse irregular pancreatic duct narrowing, compression of the intrapancreatic common bile duct, and mild proximal biliary dilatation on MR cholangiopancreatography. Laboratory results revealed normal serum IgG and subclass 4 with negative autoimmune antibodies, and slightly elevated carbohydrate antigen 19-9. This highlights the differentiation of autoimmune pancreatitis from pancreatic head cancer and, to a lesser extent, other forms of pancreatitis in children. (orig.)


    Mikhina, M S; Molashenko, N V; Troshina, E A; Orlova, E M; Sozaeva, L S; Eystein, S H; Breivik, S


    Autoimmune polyglandular syndrome is a primary autoimmune disorder affecting two or more peripheral endocrine glands and responsible for their incompetence. It is frequently combined with various organ-specific non-endocrine diseases. Patients with this pathology need life-long replacement therapy and dynamic observation by endocrinologists and other specialists to monitor the effectiveness of the treatment and detect new components of the disease. We report a variant of type 1 autoimmune polyglandular syndrome. Special emphasis is laid on the importance of succession of actions of endocrinologists and specialists in related medical disciplines dealing with children and adult patients.

  13. Is selenium supplementation in autoimmune thyroid diseases justified?

    DEFF Research Database (Denmark)

    Winther, Kristian H.; Bonnema, Steen; Hegedüs, Laszlo


    PURPOSE OF REVIEW: This review provides an appraisal of recent evidence for or against selenium supplementation in patients with autoimmune thyroid diseases, and discusses possible effect mechanisms. RECENT FINDINGS: Epidemiological data suggest an increased prevalence of autoimmune thyroid...... diseases under conditions of low dietary selenium intake. Two systematic reviews have evaluated controlled trials among patients with autoimmune thyroiditis and report that selenium supplementation decreases circulating thyroid autoantibodies. The immunomodulatory effects of selenium might involve reducing...... proinflammatory cytokine release. However, clinically relevant effects of selenium supplementation, including improvement in quality of life, are more elusive. In Graves’ disease, some, but not all, trials indicate that adjuvant selenium supplementation enhances the restoration of biochemical euthyroidism...

  14. The Epidemiologic Evidence Linking Autoimmune Diseases and Psychosis

    DEFF Research Database (Denmark)

    Benros, Michael E; Eaton, William W; Mortensen, Preben B


    diseases involve multiple organs and general dysfunction of the immune system, which could affect the brain and induce psychiatric symptoms. Most studies have been cross-sectional, observing an increased prevalence of a broad number of autoimmune diseases in people with psychotic disorders. Furthermore......, there is some evidence of associations of psychosis with a family history of autoimmune disorders and vice versa. Additionally, several autoimmune diseases, individually and in aggregate, have been identified as raising the risk for psychotic disorders in longitudinal studies. The associations have been...

  15. Autonomous Cryogenic Load Operations: Knowledge-Based Autonomous Test Engineer (United States)

    Schrading, J. Nicolas


    The Knowledge-Based Autonomous Test Engineer (KATE) program has a long history at KSC. Now a part of the Autonomous Cryogenic Load Operations (ACLO) mission, this software system has been sporadically developed over the past 20 years. Originally designed to provide health and status monitoring for a simple water-based fluid system, it was proven to be a capable autonomous test engineer for determining sources of failure in the system. As part of a new goal to provide this same anomaly-detection capability for a complicated cryogenic fluid system, software engineers, physicists, interns and KATE experts are working to upgrade the software capabilities and graphical user interface. Much progress was made during this effort to improve KATE. A display of the entire cryogenic system's graph, with nodes for components and edges for their connections, was added to the KATE software. A searching functionality was added to the new graph display, so that users could easily center their screen on specific components. The GUI was also modified so that it displayed information relevant to the new project goals. In addition, work began on adding new pneumatic and electronic subsystems into the KATE knowledge base, so that it could provide health and status monitoring for those systems. Finally, many fixes for bugs, memory leaks, and memory errors were implemented and the system was moved into a state in which it could be presented to stakeholders. Overall, the KATE system was improved and necessary additional features were added so that a presentation of the program and its functionality in the next few months would be a success.

  16. Autonomous Cryogenic Load Operations: KSC Autonomous Test Engineer (United States)

    Shrading, Nicholas J.


    The KSC Autonomous Test Engineer (KATE) program has a long history at KSC. Now a part of the Autonomous Cryogenic Load Operations (ACLO) mission, this software system has been sporadically developed over the past 20+ years. Originally designed to provide health and status monitoring for a simple water-based fluid system, it was proven to be a capable autonomous test engineer for determining sources of failure in. the system, As part.of a new goal to provide this same anomaly-detection capability for a complicated cryogenic fluid system, software engineers, physicists, interns and KATE experts are working to upgrade the software capabilities and graphical user interface. Much progress was made during this effort to improve KATE. A display ofthe entire cryogenic system's graph, with nodes for components and edges for their connections, was added to the KATE software. A searching functionality was added to the new graph display, so that users could easily center their screen on specific components. The GUI was also modified so that it displayed information relevant to the new project goals. In addition, work began on adding new pneumatic and electronic subsystems into the KATE knowledgebase, so that it could provide health and status monitoring for those systems. Finally, many fixes for bugs, memory leaks, and memory errors were implemented and the system was moved into a state in which it could be presented to stakeholders. Overall, the KATE system was improved and necessary additional features were added so that a presentation of the program and its functionality in the next few months would be a success.

  17. [A case of anti-LKM 1 positive autoimmune hepatitis accompanied by systemic lupus erythematosus]. (United States)

    Choi, Dae Han; Kim, Hae Kyung; Park, Tae Il; John, Byung Min; Kang, Sung Hwan; Lee, Yoon Serk; Kim, Tae Hyun; Lee, Uh Joo; Lee, Tae Seung; Yoon, Gwi Ok


    Overlap of autoimmune hepatitis and systemic lupus erythematosus (SLE) is a comparatively rare condition. Although both autoimmune hepatitis and SLE can share common autoimmune features such as polyarthralgia, hypergammaglobulinemia and positive ANA, it has been considered as two different entities. We report a case of anti-LKM1 positive autoimmune hepatitis who developed SLE two years later. The presence of interface hepatitis with lymphoplasma cell infiltrates and rosette formation points to the autoimmune hepatitis rather than SLE hepatitis. Autoimmune hepatitis is infrequently accompanied by SLE, therefore, it could be recommended to investigate for SLE in patients with autoimmune hepatitis.

  18. Human Supervision of Multiple Autonomous Vehicles (United States)


    AFRL-RH-WP-TR-2013-0143 HUMAN SUPERVISION OF MULTIPLE AUTONOMOUS VEHICLES Heath A. Ruff Ball...REPORT TYPE Interim 3. DATES COVERED (From – To) 09-16-08 – 03-22-13 4. TITLE AND SUBTITLE HUMAN SUPERVISION OF MULTIPLE AUTONOMOUS VEHICLES 5a...Supervision of Multiple Autonomous Vehicles To support the vision of a system that enables a single operator to control multiple next-generation

  19. The treatment of autonomic dysfunction in tetanus

    Directory of Open Access Journals (Sweden)

    T van den Heever


    Full Text Available We report a case of generalised tetanus in a 50-year-old female patient after sustaining a wound to her right lower leg. She developed autonomic dysfunction, which included labile hypertension alternating with hypotension and sweating. The autonomic dysfunction was treated successfully with a combination of morphine sulphate infusion, magnesium sulphate, and clonidine. She also received adrenaline and phenylephrine infusions as needed for hypotension. We then discuss the pathophysiology, clinical features and treatment options of autonomic dysfunction.

  20. Accelerated atherosclerosis in patients with systemic autoimmune diseases

    NARCIS (Netherlands)

    De Leeuw, K.; Kallenberg, Cees; Bijl, Marc; Shoenfeld, Y.; Gershwin, M.E.; Shoenfeld, Y; Gershwin, ME


    Systemic autoimmune diseases such as systemic lupus erythematosus and Wegener's granulomatosis are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared with age- and sex-matched controls. Many risk factors are involved in the pathogenesis of atherosclerosis,

  1. [Allergy and autoimmunity: Molecular diagnostics, therapy, and presumable pathogenesis]. (United States)

    Arefieva, A S; Smoldovskaya, O V; Tikhonov, A A; Rubina, A Yu


    Allergic and autoimmune diseases represent immunopathological reactions of an organism to antigens. Despite that the allergy is a result of exaggerated immune response to foreign antigens (allergens) and autoimmune diseases are characterized by the pathological response to internal antigens (autoantigens), the underlying mechanisms of these diseases are probably common. Thus, both types of diseases represent variations in the hypersensitivity reaction. A large percentage of both the adult and pediatric population is in need of early diagnostics of these pathologies of the immune system. Considering the diversity of antibodies produced in allergic and autoimmune disease and the difficulties accompanying clinical diagnosing, molecular diagnostics of these pathological processes should be carried out in several stages, including screening and confirmatory studies. In this review, we summarize the available data on the molecular diagnostics and therapy of allergic and autoimmune diseases and discuss the basic similarities and differences in the mechanisms of their development.

  2. The role of gut microbiota in immune homeostasis and autoimmunity. (United States)

    Wu, Hsin-Jung; Wu, Eric


    Keeping a delicate balance in the immune system by eliminating invading pathogens, while still maintaining self-tolerance to avoid autoimmunity, is critical for the body's health. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis. Moreover, it has recently become obvious that alterations of these gut microbial communities can cause immune dysregulation, leading to autoimmune disorders. Here we review the advances in our understanding of how the gut microbiota regulates innate and adaptive immune homeostasis, which in turn can affect the development of not only intestinal but also systemic autoimmune diseases. Exploring the interaction of gut microbes and the host immune system will not only allow us to understand the pathogenesis of autoimmune diseases but will also provide us new foundations for the design of novel immuno- or microbe-based therapies.

  3. Pervasive Sharing of Genetic Effects in Autoimmune Disease

    DEFF Research Database (Denmark)

    Cotsapas, Chris; Voight, Benjamin F.; Rossin, Elizabeth


    Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiologic...

  4. Associations Between Autoimmune Diseases and Attention-Deficit/Hyperactivity Disorder

    DEFF Research Database (Denmark)

    Nielsen, Philip Finn Rising; Benros, Michael Eriksen; Dalsgaard, Søren


    attention-deficit/hyperactivity disorder (ADHD). METHOD: A cohort was formed of all singletons born in Denmark from 1990 to 2007, resulting in a study population of 983,680 individuals followed from 1995 to 2012. Information on autoimmune diseases was obtained from the Danish National Hospital Register......OBJECTIVE: Recent studies have suggested that autoimmune diseases and immune activation play a part in the pathogenesis of different neurodevelopmental disorders. This study investigated the association between a personal history and a family history of autoimmune disease and the risk of developing....... Individuals with ADHD were identified through the Danish National Hospital Register and the Danish Psychiatric Central Register. RESULTS: In total, 23,645 children were diagnosed with ADHD during the study period. Autoimmune disease in the individual was associated with an increased risk of ADHD...

  5. [Treatment and results of therapy in autoimmune hemolytic anemia]. (United States)

    Tasić, J; Macukanović, L; Pavlović, M; Koraćević, S; Govedarević, N; Kitić, Lj; Tijanić, I; Bakić, M


    Basic principles in the therapy of idiopathic autoimmune hemolytic anemia induced by warm antibody were glucocorticoides and splenectomy. Immunosupresive drugs, plasmaferesis and intravenous high doses gamma globulin therapy are also useful. In secundary autoimmune hemolytic anemia induced by warm antibody we treated basic illness. During the period of 1990-1992 we treated 21 patients with primary autoimmune hemolytic anemia and 6 patients with secondary /4 CLL and 2 Non-Hodgkin's lymphoma/. Complete remission we found as a normalisation of reticulocites and hemoglobin level respectively. Complete remission by corticoides we got in 14/21 patients, partial response in 2/21 respectively. Complete response by splenectomy we got in 2/3 splenoctomized patients (idiopathic type). For successful treatment secondary hemolytic anemias we treated primary diseases (CLL and malignant lymphoma) and we got in 4/6 patients complete remission. Our results were standard in both type of autoimmune hemolytic anaemias induced by warm antibody.

  6. Autoimmunity in differentiated thyroid cancer: significance and related clinical problems

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Rasmussen, Ase Krogh


    Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune diseases could represent a mere coincidence due to the frequent occurrence of autoimmunity, but there may also be a pathological and causative link between the two conditions. The coincidence of DTC with Hashimoto's disease...... has been variably reported at between 0.5 and 22.5% and of DTC with Graves' disease between 0 and 9.8%. In this review available evidence for thyroid autoimmunity in DTC is summarized and it is concluded that thyroid cancer does coexist with thyroid autoimmunity, implying that patients treated...... TgAb measurements may be used as a surrogate marker for recurrence of thyroid cancer during the long-term monitoring of DTC patients....

  7. Autoimmunity in differentiated thyroid cancer: significance and related clinical problems

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Rasmussen, Ase Krogh


    Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune diseases could represent a mere coincidence due to the frequent occurrence of autoimmunity, but there may also be a pathological and causative link between the two conditions. The coincidence of DTC with Hashimoto's disease...... has been variably reported at between 0.5 and 22.5% and of DTC with Graves' disease between 0 and 9.8%. In this review available evidence for thyroid autoimmunity in DTC is summarized and it is concluded that thyroid cancer does coexist with thyroid autoimmunity, implying that patients treated...... TgAb measurements may be used as a surrogate marker for recurrence of thyroid cancer during the long-term monitoring of DTC patients....

  8. Auto-immune haematological complications occurring during the ...

    African Journals Online (AJOL)

    Auto-immune haematological complications occurring during treatment for malignant Iymphoproliferative diseases are described in 5 patients. There appeared to be a temporal relationship between the development of these complications and the administration of chemotherapeutic drugs or extensive radiotherapy.

  9. Diagnosis and Management of the Overlap Syndromes of Autoimmune Hepatitis

    Directory of Open Access Journals (Sweden)

    Albert J Czaja


    Full Text Available BACKGROUND: Autoimmune hepatitis may have cholestatic features that are outside the classical phenotype and that resemble findings in other immune-mediated liver diseases. These cholestatic phenotypes have been designated ‘overlap syndromes’.

  10. Cardiovascular disease in autoimmune rheumatic diseases. (United States)

    Hollan, Ivana; Meroni, Pier Luigi; Ahearn, Joseph M; Cohen Tervaert, J W; Curran, Sam; Goodyear, Carl S; Hestad, Knut A; Kahaleh, Bashar; Riggio, Marcello; Shields, Kelly; Wasko, Mary C


    Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and non-traditional risk factors. Besides other factors, inflammation and immunologic abnormalities, the quantity and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia, obesity and underweight, presence of platelets bearing complement protein C4d, reduced number and function of endothelial progenitor cells, apoptosis of endothelial cells, epigenetic mechanisms, renal disease, periodontal disease, depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency may contribute to the premature CVD. Although most research has focused on systemic inflammation, vascular inflammation may play a crucial role in the premature CVD in ARDs. It may be involved in the development and destabilization of both atherosclerotic lesions and of aortic aneurysms (a known complication of ARDs). Inflammation in subintimal vascular and perivascular layers appears to frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients. It is possible that this inflammation is caused by infections and/or autoimmunity, which might have consequences for treatment. Importantly, drugs targeting immunologic factors participating in the subintimal inflammation (e.g., T- and B-cells) might have a protective effect on CVD. Interestingly, vasa vasorum and cardiovascular adipose tissue may


    Directory of Open Access Journals (Sweden)

    Pavankumar Tandra


    Full Text Available CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5+ B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA is the most common autoimmune complication of CLL and has been reported in 10-25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT is positive in 7-14% of CLL patients but AIHA may also occur in DAT negative patients. Autoimmune thrombocytopenia (AIT is the second most common complication of CLL and has been reported in 2-3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN and pure red cell aplasia (PRCA are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL. Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD, paraneoplastic pemphigus (PNP, acquired angioedema, and anti-myelin associated globulin are rare. Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg, cyclosporine, and rituximab are used in

  12. Role of autoimmunity in nonviral chronic liver disease. (United States)

    Amarapurkar, D N; Amarapurkar, A D


    To evaluate the prevalence and clinical profile of autoimmune hepatitis (AIH) in patients with chronic liver disease. Four hundred and thirty five consecutive patient with chronic liver disease seen in our department from January 1997 to December 1998 were studied with detailed history and clinical examination. All the patients underwent liver function tests, ultrasonography, isotope liver scanning, viral markers, autoimmune markers ANA, ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever permissible. Appropriate work up for Wilson's disease was done whenever suspected clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring system by international autoimmune hepatitis group. Twenty out of the 435 patients met the criteria of definite autoimmune hepatitis and seven patient had probable autoimmune hepatitis. Forty out of 408 patients showed markers of autoimmunity positive but did not qualify diagnosis of AIH on composite scores. Demographic profile of 27 patients with autoimmune hepatitis was as follows; male:female ratio 1:8, mean age 39.8 +/- 13 years (Range 4-65 years); mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%) and acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12 (44.4%) patients while mean serum aminotransferases levels were 249 +/- 343 and 262 +/- 418 respectively. Other disease associations seen were as follows: diabetes in 4 (14.8%), rheumatoid arthritis in 3 (11%), hypothyroidism in 2 (7.4%) and ulcerative colitis in 1 (3.7%). The pattern of autoimmune markers was ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children), ASMA +ve in 16/27 (59.2%) (+ve titres of ASMA > 1:40) and LKM1 in 3 patients. AMA in tires less than 1:80 was found in 3 patients. Liver histology changes seen were lymphoplasmacytic infiltrates (100%), bridging necrosis (93%), liver cell rossetting (80%) and fibrosis with or without cirrhosis (50

  13. Public Health, Ethics, and Autonomous Vehicles. (United States)

    Fleetwood, Janet


    With the potential to save nearly 30 000 lives per year in the United States, autonomous vehicles portend the most significant advance in auto safety history by shifting the focus from minimization of postcrash injury to collision prevention. I have delineated the important public health implications of autonomous vehicles and provided a brief analysis of a critically important ethical issue inherent in autonomous vehicle design. The broad expertise, ethical principles, and values of public health should be brought to bear on a wide range of issues pertaining to autonomous vehicles.

  14. A Generic Architecture for Autonomous Uninhabited Vehicles

    National Research Council Canada - National Science Library

    Barbier, Magali; Gabard, Jean-Francois; Ayreault, Herve


    ...; few solutions propose architecture adaptive to several types of platform. Autonomous vehicles that move in partially known and dynamic environments have to deal with asynchronous disruptive events...

  15. Research Institute for Autonomous Precision Guided Systems

    National Research Council Canada - National Science Library

    Rogacki, John R


    ... actuators, development of a visualization lab for modeling vision based guidance algorithms, concept development of a rapid prototyping and aero characterization lab, vision based control of autonomous...

  16. Autoimmune/Inflammatory Arthritis Associated Lymphomas: Who Is at Risk?


    Yadlapati, Sujani; Efthimiou, Petros


    Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA), primary Sjögren’s syndrome (pSS), systemic lupus erythematosus (SLE), dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and ly...

  17. Progress in diagnosis and treatment of autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    YIN Tao


    Full Text Available Autoimmune pancreatitis (AIP is a special type of chronic pancreatitis that originates from an autoimmune-mediated mechanism. AIP has unique radiological, serological, and histopathological features, often accompanied by peripancreatic lesions. AIP may be easily confused with pancreatic cancer and cholangiocarcinoma. It is necessary to diagnose AIP while integrating a variety of clinical indicators. Steroid therapy should be performed for patients diagnosed with AIP, and surgical treatment can be selected if necessary.

  18. High prevalence of autoimmune urticaria in children with chronic urticaria

    DEFF Research Database (Denmark)

    Brunetti, Luigia; Francavilla, Ruggiero; Miniello, Vito L


    The etiology of chronic urticaria (CU) in childhood often remains unrecognized. Recently, in adults it has been shown that approximately 40% of patients with CU have autoimmune urticaria (AU); however, no data are available in children.......The etiology of chronic urticaria (CU) in childhood often remains unrecognized. Recently, in adults it has been shown that approximately 40% of patients with CU have autoimmune urticaria (AU); however, no data are available in children....

  19. Autoimmune Disease with Cardiac Valves Involvement: Libman-Sacks Endocarditis. (United States)

    Ginanjar, Eka; Yulianto, Yulianto


    This case study aim to evaluate the response of steroid treatment for autoimmune endocarditis. Valvular heart disease is relatively rising in both congenital and acquired cases, but the autoimmune endocarditis remains rare. In this case, a 34 year old woman with clinical manifestation resembling systemic lupus erythematosus (SLE) is diagnosed with Libman-sacks Endocarditis. After six months of steroid treatment, her clinical manifestations and heart structure improved.

  20. A Girl with Autoimmune Cytopenias, Nonmalignant Lymphadenopathy, and Recurrent Infections

    Directory of Open Access Journals (Sweden)

    Marjolein A. C. Mattheij


    Full Text Available We describe a girl, now 9 years of age, with chronic idiopathic thrombocytopenic purpura, persistent nonmalignant lymphadenopathy, splenomegaly, recurrent infections, and autoimmune hemolytic anemia. Her symptoms partly fit the definitions of both autoimmune lymphoproliferative syndrome (ALPS and common variable immunodeficiency disorders (CVIDs. Genetic analysis showed no abnormalities in the ALPS-genes FAS, FASLG, and CASP10. The CVID-associated TACI gene showed a homozygous polymorphism (Pro251Leu, which is found also in healthy controls.

  1. Autoimmune diseases and severe infections as risk factors for schizophrenia

    DEFF Research Database (Denmark)

    Benros, Michael E; Nielsen, Philip R; Nordentoft, Merete


    Autoimmune diseases have been associated with an increased risk of schizophrenia. It has been suggested that brain-reactive autoantibodies are part of the mechanisms behind this association. Furthermore, an increased permeability of the blood-brain barrier has been observed during periods...... of infection and inflammation. The authors therefore investigated whether autoimmune diseases combined with exposures to severe infections may increase the risk of schizophrenia...

  2. Autonomous Real Time Requirements Tracing (United States)

    Plattsmier, George; Stetson, Howard


    One of the more challenging aspects of software development is the ability to verify and validate the functional software requirements dictated by the Software Requirements Specification (SRS) and the Software Detail Design (SDD). Insuring the software has achieved the intended requirements is the responsibility of the Software Quality team and the Software Test team. The utilization of Timeliner-TLX(sup TM) Auto- Procedures for relocating ground operations positions to ISS automated on-board operations has begun the transition that would be required for manned deep space missions with minimal crew requirements. This transition also moves the auto-procedures from the procedure realm into the flight software arena and as such the operational requirements and testing will be more structured and rigorous. The autoprocedures would be required to meet NASA software standards as specified in the Software Safety Standard (NASASTD- 8719), the Software Engineering Requirements (NPR 7150), the Software Assurance Standard (NASA-STD-8739) and also the Human Rating Requirements (NPR-8705). The Autonomous Fluid Transfer System (AFTS) test-bed utilizes the Timeliner-TLX(sup TM) Language for development of autonomous command and control software. The Timeliner-TLX(sup TM) system has the unique feature of providing the current line of the statement in execution during real-time execution of the software. The feature of execution line number internal reporting unlocks the capability of monitoring the execution autonomously by use of a companion Timeliner-TLX(sup TM) sequence as the line number reporting is embedded inside the Timeliner-TLX(sup TM) execution engine. This negates I/O processing of this type data as the line number status of executing sequences is built-in as a function reference. This paper will outline the design and capabilities of the AFTS Autonomous Requirements Tracker, which traces and logs SRS requirements as they are being met during real-time execution of the

  3. Autonomous sensor manager agents (ASMA) (United States)

    Osadciw, Lisa A.


    Autonomous sensor manager agents are presented as an algorithm to perform sensor management within a multisensor fusion network. The design of the hybrid ant system/particle swarm agents is described in detail with some insight into their performance. Although the algorithm is designed for the general sensor management problem, a simulation example involving 2 radar systems is presented. Algorithmic parameters are determined by the size of the region covered by the sensor network, the number of sensors, and the number of parameters to be selected. With straight forward modifications, this algorithm can be adapted for most sensor management problems.

  4. Autonomously managed electrical power systems (United States)

    Callis, Charles P.


    The electric power systems for future spacecraft such as the Space Station will necessarily be more sophisticated and will exhibit more nearly autonomous operation than earlier spacecraft. These new power systems will be more reliable and flexible than their predecessors offering greater utility to the users. Automation approaches implemented on various power system breadboards are investigated. These breadboards include the Hubble Space Telescope power system test bed, the Common Module Power Management and Distribution system breadboard, the Autonomusly Managed Power System (AMPS) breadboard, and the 20 kilohertz power system breadboard. Particular attention is given to the AMPS breadboard. Future plans for these breadboards including the employment of artificial intelligence techniques are addressed.

  5. Autonomous quality assurance and troubleshooting (United States)

    DuPlain, Ronald F.; Radziwill, Nicole M.; Shelton, Amy L.


    To improve operational availability (the proportion of time that a telescope is able to accomplish what a visiting observer wants at the time the observation is scheduled), response time to faults must be minimized. One way this can be accomplished is by characterizing the relationships and interdependencies between components in a control system, developing algorithms to identify the root cause of a problem, and capturing expert knowledge of a system to simplify the process of troubleshooting. Results from a prototype development are explained, along with deployment issues. Implications for the future, such as effective knowledge representation and management, and learning processes which integrate autonomous and interactive components, are discussed.

  6. Artificial Intelligence in Autonomous Telescopes (United States)

    Mahoney, William; Thanjavur, Karun


    Artificial Intelligence (AI) is key to the natural evolution of today's automated telescopes to fully autonomous systems. Based on its rapid development over the past five decades, AI offers numerous, well-tested techniques for knowledge based decision making essential for real-time telescope monitoring and control, with minimal - and eventually no - human intervention. We present three applications of AI developed at CFHT for monitoring instantaneous sky conditions, assessing quality of imaging data, and a prototype for scheduling observations in real-time. Closely complementing the current remote operations at CFHT, we foresee further development of these methods and full integration in the near future.

  7. Topological entropy of autonomous flows

    Energy Technology Data Exchange (ETDEWEB)

    Badii, R. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)


    When studying fluid dynamics, especially in a turbulent regime, it is crucial to estimate the number of active degrees of freedom or of localized structures in the system. The topological entropy quantifies the exponential growth of the number of `distinct` orbits in a dynamical system as a function of their length, in the infinite spatial resolution limit. Here, I illustrate a novel method for its evaluation, which extends beyond maps and is applicable to any system, including autonomous flows: these are characterized by lack of a definite absolute time scale for the orbit lengths. (author) 8 refs.

  8. BART: The Czech Autonomous Observatory

    Czech Academy of Sciences Publication Activity Database

    Nekola, Martin; Hudec, René; Jelínek, M.; Kubánek, P.; Štrobl, Jan; Polášek, Cyril


    Roč. 2010, Spec. Is. (2010), 103986/1-103986/5 ISSN 1687-7969. [Workshop on Robotic Autonomous Observatories. Málaga, 18.05.2009-21.05.2009] R&D Projects: GA ČR GA205/08/1207 Grant - others:ESA(XE) ESA-PECS project No. 98023; Spanish Ministry of Education and Science(ES) AP2003-1407 Institutional research plan: CEZ:AV0Z10030501 Keywords : robotic telescope * BART * gamma ray bursts Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics

  9. The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease. (United States)

    Kerr, Jonathan R


    Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised. Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic. Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus. B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  10. Autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis

    Directory of Open Access Journals (Sweden)

    Pejin Radoslav


    Full Text Available Introduction. Autoimmune polyglandular syndrome type 2 is defined as adrenal insufficiency associated with autoimmune primary hypothyroidism and/or with autoimmune type 1 diabetes mellitus, but very rare with myasthenia gravis. Case report. We presented a case of an autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis. A 49-year-old female with symptoms of muscle weakness and low serum levels of cortisol and aldosterone was already diagnosed with primary adrenal insufficiency. Primary hypothyroidism was identified with low values of free thyroxine 4 (FT4 and raised values of thyroidstumulating hormone (TSH. The immune system as a cause of hypothyroidism was confirmed by the presence of thyroid antibodies to peroxidase and TSH receptors. Myasthenia gravis was diagnosed on the basis of a typical clinical feature, positive diagnostic tests and an increased titre of antibodies against the acetylcholine receptors. It was not possible to confirm the immune nature of adrenal insufficiency by the presence of antibodies to 21- hydroxylase. The normal morphological finding of the adrenal glands was an indirect confirmation of the condition as well as the absence of other diseases that might have led to adrenal insufficiency and low levels of both serum cortisol and aldosterone. Hormone replacement therapy, anticholinergic therapy and corticosteroid therapy for myasthenia gravis improved the patient’s general state of health and muscle weakness. Conclusion. This case report indicates a need to examine each patient with an autoimmune disease carefully as this condition may be associated with another autoimmune diseases.

  11. Thyroid autoimmunity in bipolar disorder: A systematic review. (United States)

    Barbuti, Margherita; Carvalho, André F; Köhler, Cristiano A; Murru, Andrea; Verdolini, Norma; Guiso, Giovanni; Samalin, Ludovic; Maes, Michael; Stubbs, Brendon; Perugi, Giulio; Vieta, Eduard; Pacchiarotti, Isabella


    Accumulating evidence points to the pathophysiological relevance between immune dysfunction and mood disorders. High rates of thyroid dysfunction have been found in patients with bipolar disorder (BD), compared to the general population. A systematic review of the relationship between BD and thyroid autoimmunity was performed. Pubmed, EMBASE and PsycINFO databases were searched up till January 28th, 2017. This review has been conducted according to the PRISMA statements. Observational studies clearly reporting data among BD patients and the frequency of autoimmune thyroid pathologies were included. 11 original studies met inclusion criteria out of 340 titles first returned from the global search. There is evidence of increased prevalence of circulating thyroid autoantibodies in depressed and mixed BD patients, while there is no evidence showing a positive relationship between BD and specific autoimmune thyroid diseases. There is a controversy about the influence of lithium exposure on circulating thyroid autoantibodies, even if most of studies seem not to support this association. A study conducted on bipolar twins suggests that autoimmune thyroiditis is related to the genetic vulnerability to develop BD rather than to the disease process itself. Females are more likely to develop thyroid autoimmunity. The samples, study design and outcomes were heterogeneous. Thyroid autoimmunity has been suggested to be an independent risk factor for bipolar disorder with no clear association with lithium exposure and it might serve as an endophenotype for BD. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Differences between older and young patients with autoimmune gastritis. (United States)

    Kalkan, Çağdaş; Soykan, Irfan


    Elderly patients with autoimmune gastritis might have different symptoms than those of young patients. The aim of the present study was to compare presented symptoms and laboratory parameters associated with autoimmune gastritis in both old and young age groups. A total of 355 patients with autoimmune gastritis were stratified into two groups: 65 years or older (n = 119, mean age 69.47 ± 5.027 years), and under 65 years (n = 236, mean age 45.79 ± 10.51 years). These two groups were then evaluated and compared by means of clinical symptoms, concurrent autoimmune diseases, serum gastrin, vitamin B 12 and chromogranin A levels, and the presence of enterochromograffin-like cell hyperplasia. Among 119 older patients, 35 had dyspeptic symptoms, and 84 patients were referred for vitamin B 12 and/or iron deficiency. In the younger group (n = 236), there were more patients who had dyspeptic symptoms (36 vs 200, P gastritis that are older and younger than 65 years-of-age. Elderly patients with autoimmune gastritis were investigated more commonly for vitamin B 12 and/or iron deficiency. Polyautoimmunity and multiple autoimmune syndrome were more common, and serum gastrin and chromogranin A levels were significantly higher in older patients. Geriatr Gerontol Int 2017; 17: 1090-1095. © 2016 Japan Geriatrics Society.

  13. Naturally Occurring Anthraquinones: Chemistry and Therapeutic Potential in Autoimmune Diabetes

    Directory of Open Access Journals (Sweden)

    Shih-Chang Chien


    Full Text Available Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, anti-inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes.

  14. The Immunopathogenesis of Chronic Autoimmune Thyroiditis One Century after Hashimoto (United States)

    Weetman, Anthony P


    Hakaru Hashimoto described 4 patients with a hitherto unknown cause for goitre, struma lymphomatosa, a century ago. He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related sclerosing disease may be an outcome. Although the cause of the lymphocytic infiltration was unknown to Hashimoto, we now know through the pioneering studies of N.R. Rose and E. Witebsky [J Immunol 1956;76:417–427] that this condition is the archetype for autoimmune destruction as a disease mechanism. In the last two decades in particular, there has been huge interest in unravelling the genetic basis for this and related autoimmune disorders. The list of polymorphisms associated with autoimmune thyroid disease grows each year, and in the case of vitiligo, which is frequently found in association with thyroid autoimmunity, we know that 27 separate susceptibility loci account for less than 20% of the heritability of this condition. Environmental and existential factors may turn out to be just as complex in number and in interactions. We can thus imagine a ‘Swiss cheese’ model for the causation of autoimmune thyroid disease, in which the effects of cumulative weaknesses line up – like the holes in slices of cheese – to allow the catastrophic event of autoimmune destruction to occur. PMID:24783026

  15. Autoimmune hepatitis in children: what is different from adult AIH? (United States)

    Mieli-Vergani, Giorgina; Vergani, Diego


    Autoimmune hepatitis (AIH) is characterized by inflammatory liver histology, circulating non-organ-specific autoantibodies, and increased levels of immunoglobulin (Ig) G in the absence of a known etiology. Two types of childhood AIH are recognized according to seropositivity: smooth muscle antibody (SMA) and/or antinuclear antibody (ANA), which is AIH type 1; and antibodies to liver-kidney microsome type 1 (anti-LKM1), which is AIH type 2. There is a female predominance in both. Autoimmune hepatitis type 2 presents more acutely, at a younger age, and commonly with IgA deficiency; however, duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the two groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. The differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis, liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. Copyright Thieme Medical Publishers.

  16. Diagnosis and therapy of autoimmune hepatitis. (United States)

    Granito, Alessandro; Muratori, Paolo; Ferri, Silvia; Pappas, Georgios; Quarneti, Chiara; Lenzi, Marco; Bianchi, Francesco B; Muratori, Luigi


    Autoimmune hepatitis (AIH) is a chronic progressive hepatitis, characterized by interface hepatitis with lymphoplasmacellular infiltrates on liver biopsy, high serum globulin level and circulating autoantibodies. It is classified into two types, according to autoantibody profile: type 1 is characterized by anti-nuclear (ANA) and/or anti-smooth muscle (SMA) antibodies; type 2 by anti-liver kidney microsomal type 1 (anti-LKM-1) antibodies. AIH affects all ages, may be asymptomatic, frequently has an acute onset, and can present as fulminant hepatitis. The diagnosis of AIH is based on a scoring system codified by an international consensus. Corticosteroids alone or in conjunction with azathioprine is the treatment of choice in patients with AIH and results in remission induction in over 80% of patients. Alternative proposed strategies in patients who have failed to achieve remission on standard therapy or patients with drug toxicity include the use of cyclosporine, tacrolimus, budesonide or mycophenolate mofetil. Liver transplantation is the treatment of choice in managing decompensated disease, however AIH can recur or develop de novo after liver transplantation.

  17. Autoimmune pancreatitis - the story so far

    International Nuclear Information System (INIS)

    Jackson, S.


    Full text: Learning objectives: to learn about the main imaging diagnostic findings of AIP and the International Consensus Diagnostic Criteria (ICDC); to understand the best strategies for distinguishing AIP from pancreatic cancer; to emphasise the central role of radiology in the era of “clinical decision making” Autoimmune Pancreatitis (AIP) was first described in 1961 and represents a rare form of immune mediated chronic pancreatitis which is characterised by a marked infiltration of lymphocytes and plasma cells into pancreatic tissue. Whilst the majority of cases present with diffuse gland involvement, approximately 30% of patient’s demonstrate either segmental or focal involvement of the pancreas. Clinical presentation is very variable with patients describing a range of symptoms. Imaging plays a central role in the diagnosis and management of AIP and knowledge of the radiological appearances, which can vary significantly due to the various degrees of fibrosis and inflammatory infiltrate, is critical. Cardinal features include focal or diffuse pancreatic enlargement with the loss of normal lobular architecture. Post contrast enhancement features of the pancreas may also be useful. In addition, pancreatic duct involvement as demonstrated by single or multiple focal strictures with limited more proximal dilatation is common as well as infiltration of the common bile duct.Whilst multimodality appearances may suggest a diagnosis of AIP correlation with clinical history, serology and histopathology is mandatory in order to accurately diagnose atypical cases

  18. New Genetic Insights from Autoimmune Thyroid Disease

    Directory of Open Access Journals (Sweden)

    Terry F. Davies


    Full Text Available The autoimmune thyroid diseases (AITDs (Graves’ disease and Hashimoto’s thyroiditis are complex genetic diseases which most likely have more than 20 genes contributing to the clinical phenotypes. To date, the genes known to be contributing fall into two categories: immune regulatory genes (including HLA, CTLA4, PTPN22, CD40, CD25, and FCRL3 and thyroid-specific genes (TG and TSHR. However, none of these genes contribute more than a 4-fold increase in risk of developing one of these diseases, and none of the polymorphisms discovered is essential for disease development. Hence, it appears that a variety of different gene interactions can combine to cause the same clinical disease pattern, but the contributing genes may differ from patient to patient and from population to population. Furthermore, this possible mechanism leaves open the powerful influence of the environment and epigenetic modifications of gene expression. For the clinician, this means that genetic profiling of such patients is unlikely to be fruitful in the near future.

  19. Autoimmune pancreatitis: An illustrated guide to diagnosis

    International Nuclear Information System (INIS)

    Proctor, R.D.; Rofe, C.J.; Bryant, T.J.C.; Hacking, C.N.; Stedman, B.


    Autoimmune pancreatitis (AIP) remains one of the rarer forms of pancreatitis but has become increasingly well recognized and widely diagnosed as it is an important differential, particularly due to the dramatic response to appropriate therapy. It is now best considered as part of a multisystem disease and the notion of “IgG4-related systemic sclerosing disease” has become widely recognized as the number of extra-pancreatic associations of AIP grows. More recently AIP has been classified into two subtypes: lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP) with distinct geographical, age and sex distributions for the two subtypes, in addition to different pathological characteristics. The role of imaging is crucial in AIP and should be considered in conjunction with clinical, serological, and histopathological findings to make the diagnosis. Radiologists are uniquely placed to raise the possibility of AIP and aid the exclusion of significant differentials to allow the initiation of appropriate management and avoidance of unnecessary intervention. Radiological investigation may reveal a number of characteristic imaging findings in AIP but appearances can vary considerably and the focal form of AIP may appear as a pancreatic mass, imitating pancreatic carcinoma. This review will illustrate typical and atypical appearances of AIP on all imaging modes. Emphasis will be placed on the imaging features that are likely to prove useful in discriminating AIP from other causes prior to histopathological confirmation. In addition, examples of relevant differential diagnoses are discussed and illustrated

  20. [Antibodies and physiopathogeny of autoimmune hepatitis]. (United States)

    García-Leiva, Jorge; Ríos-Vaca, Aurelio; Torre-Delgadillo, Aldo


    Autoimmune hepatitis (AIH) is an inflammatory disease of unknown cause characterized by periportal hepatitis, increased serum globulins and the presence of certain antibodies. The disorder can be classified in three types. Type 1 AIH is characterized by the presence of antinuclear antibodies (ANA) and smooth muscle autoantibodies (SMA) in up to 70-80% of patients. ANA and SMA can be the only antibodies present in 13 and 33% of cases respectively. Type 2 AIH is defined by the presence of liver and kidney antimicrosomal antibodies (LKM1). Type 2 AIH is the only form of the disease in which the autoantigen has been identified: cytochrome mono-oxygenase (P-450 IID6) CYP2D6. In type 3 AIH the presence of anti-SLA/LP (soluble liver antigen/liver pancreas) targets a cytosolic protein involved in the incorporation of selenocysteine into peptidic chains. The pathophysiology of AIH is complex and involves genetic predisposition, previous exposure to antigens (autoantigens), presence of triggering factors and defects in immunoregulation. In spite of the advances in the understanding of AIH, the role of autoantibodies in the pathophysiology of this disease has not been fully established and their presence does not clearly distinguish any prognostic groups. Further investigations will help in the diagnosis of this disorder, the comprehension of its origins and the establishment of new forms of treatment.

  1. Autoantibodies and their antigens in autoimmune hepatitis. (United States)

    Bogdanos, Dimitrios P; Mieli-Vergani, Giorgina; Vergani, Diego


    Autoantibody detection assists in the diagnosis and allows differentiation of autoimmune hepatitis (AIH) type 1 (AIH-1), characterized by antinuclear antibody (ANA) and/or smooth muscle antibody (SMA), and type 2 (AIH-2), distinguished by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) and/or antibodies to liver cytosol type 1 (anti-LC1). Detection of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-soluble liver antigen (SLA) antibodies can act as an additional pointer toward the diagnosis of AIH, particularly in the absence of the conventional autoantibodies. Routine autoantibody testing by indirect immunofluorescence has been recently complemented by molecular assays based on purified or recombinant antigens. Although the AIH-1-specific ANA and SMA targets need better definition, those of anti-LKM1 and anti-LC1 in AIH-2 have been clearly identified; the fine specificity of antibody reactivity and its clinical relevance to disease pathogenesis are the focus of ongoing investigation. This article critically discusses the current knowledge of the diagnostic and clinical significance of AIH-related autoantibody reactivities, focusing on key issues that the physician needs to be aware of to be able to request the appropriate testing and to interpret correctly the laboratory results within the clinical context of the patient. Copyright Thieme Medical Publishers.

  2. Nongoitrous autoimmune thyroiditis with facial palsy

    Directory of Open Access Journals (Sweden)

    Hyung Jik Lee


    Full Text Available We report a case of severe hypothyroidism with nongoitrous, autoimmune thyroiditis and pituitary hyperplasia in a 13-year-old boy, who presented with sudden palsy on the left side of his face. Prednisolone and antiviral medication was administered. However, the facial palsy did not improve completely. The medications were replaced with thyroxine, and the facial palsy recovered. Endocrinological testing showed severe hypothyroidism as follows: thyroid stimulating hormone (TSH level >100 µIU/mL, T4 of 1.04 µg/dL, T3 of 0.31 ng/mL, and free T4 of 0.07 ng/dL. Level of serum antithyroid peroxidase antibodies was 1,933.39 IU/mL, and that of antithyroglobulin antibodies was 848.16 IU/mL. Level of TSH receptor antibodies was >40 IU/L. Bioassay result for TSH receptor stimulating antibodies was negative. Thyroid sonography revealed no increase in the size or vascularity of the bilateral gland. Thyroid scintigraphy with 99mTc showed decreased uptake, and magnetic resonance imaging demonstrated an enlarged pituitary gland.

  3. Understanding Autoimmunity of Vitiligo and Alopecia Areata (United States)

    Rork, Jillian F.; Rashighi, Mehdi; Harris, John E.


    Purpose of review Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include non-targeted approaches such as corticosteroids, topical calcineurin inhibitors, narrow band UVB phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments. Recent findings Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFN-γ, IFN-γ-induced chemokines, and cytotoxic CD8+ T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis. Summary The identification of IFN-γ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials. PMID:27191524

  4. Putative golden proportions as predictors of facial esthetics in adolescents.

    NARCIS (Netherlands)

    Kiekens, R.M.A.; Kuijpers-Jagtman, A.M.; Hof, M.A. van 't; Hof, B.E. van 't; Maltha, J.C.


    INTRODUCTION: In orthodontics, facial esthetics is assumed to be related to golden proportions apparent in the ideal human face. The aim of the study was to analyze the putative relationship between facial esthetics and golden proportions in white adolescents. METHODS: Seventy-six adult laypeople

  5. Exploring universal partnerships and putative marriages as tools for ...

    African Journals Online (AJOL)

    Following upon the Supreme Court of Appeal's judgment in Butters v Mncora 2012 4 SA 1 (SCA), which broadened the criteria and consequences of universal partnerships in cohabitation relationships, this article investigates the potential of universal partnerships and putative marriages to allocate rights to share in ...

  6. Putative Lineage of Novel African Usutu Virus, Central Europe

    Centers for Disease Control (CDC) Podcasts


    Sarah Gregory reads an abridged version of "Putative Lineage of Novel African Usutu Virus, Central Europe.".  Created: 10/15/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 10/15/2015.

  7. Computational identification of putative cytochrome P450 genes in ...

    African Journals Online (AJOL)

    In this work, a computational study of expressed sequence tags (ESTs) of soybean was performed by data mining methods and bio-informatics tools and as a result 78 putative P450 genes were identified, including 57 new ones. These genes were classified into five clans and 20 families by sequence similarities and among ...

  8. Differential expressions of putative genes in various floral organs of ...

    African Journals Online (AJOL)



    Jun 3, 2009 ... Full Length Research Paper. Differential expressions of putative genes in various floral organs of the Pigeon orchid (Dendrobium crumenatum) using GeneFishing. Faridah, Q. Z.1, 2, Ng, B. Z.3, Raha, A. R.4, Umi, K. A. B.5 and Khosravi, A. R.2*. 1Department of Biology, Faculty Science, University Putra ...

  9. Inhibitory Synaptic Plasticity - Spike timing dependence and putative network function.

    Directory of Open Access Journals (Sweden)

    Tim P Vogels


    Full Text Available While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical □ndings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.

  10. Alkenenitrile Transmissive Olefination: Synthesis of the Putative Lignan "Morinol I" (United States)

    Fleming, Fraser F.; Liu, Wang; Yao, Lihua; Pitta, Bhaskar; Purzycki, Matthew; Ravikumar, P. C.


    Grignard reagents trigger an addition-elimination with α'-hydroxy acrylonitriles to selectively generate Z-alkenenitriles. The modular assembly of Z-alkenenitriles from a Grignard reagent, acrylonitrile, and an aldehyde is ideal for stereoselectively synthesizing alkenes as illustrated in the synthesis of the putative lignan "morinol I." PMID:22545004

  11. Autonomous Lawnmower using FPGA implementation. (United States)

    Ahmad, Nabihah; Lokman, Nabill bin; Helmy Abd Wahab, Mohd


    Nowadays, there are various types of robot have been invented for multiple purposes. The robots have the special characteristic that surpass the human ability and could operate in extreme environment which human cannot endure. In this paper, an autonomous robot is built to imitate the characteristic of a human cutting grass. A Field Programmable Gate Array (FPGA) is used to control the movements where all data and information would be processed. Very High Speed Integrated Circuit (VHSIC) Hardware Description Language (VHDL) is used to describe the hardware using Quartus II software. This robot has the ability of avoiding obstacle using ultrasonic sensor. This robot used two DC motors for its movement. It could include moving forward, backward, and turning left and right. The movement or the path of the automatic lawn mower is based on a path planning technique. Four Global Positioning System (GPS) plot are set to create a boundary. This to ensure that the lawn mower operates within the area given by user. Every action of the lawn mower is controlled by the FPGA DE' Board Cyclone II with the help of the sensor. Furthermore, Sketch Up software was used to design the structure of the lawn mower. The autonomous lawn mower was able to operate efficiently and smoothly return to coordinated paths after passing the obstacle. It uses 25% of total pins available on the board and 31% of total Digital Signal Processing (DSP) blocks.

  12. Structured control for autonomous robots

    International Nuclear Information System (INIS)

    Simmons, R.G.


    To operate in rich, dynamic environments, autonomous robots must be able to effectively utilize and coordinate their limited physical and occupational resources. As complexity increases, it becomes necessary to impose explicit constraints on the control of planning, perception, and action to ensure that unwanted interactions between behaviors do not occur. This paper advocates developing complex robot systems by layering reactive behaviors onto deliberative components. In this structured control approach, the deliberative components handle normal situations and the reactive behaviors, which are explicitly constrained as to when and how they are activated, handle exceptional situations. The Task Control Architecture (TCA) has been developed to support this approach. TCA provides an integrated set of control constructs useful for implementing deliberative and reactive behaviors. The control constructs facilitate modular and evolutionary system development: they are used to integrate and coordinate planning, perception, and execution, and to incrementally improve the efficiency and robustness of the robot systems. To date, TCA has been used in implementing a half-dozen mobile robot systems, including an autonomous six-legged rover and indoor mobile manipulator

  13. Spontaneous autoimmunity in 129 and C57BL/6 mice-implications for autoimmunity described in gene-targeted mice.

    Directory of Open Access Journals (Sweden)

    Anne E Bygrave


    Full Text Available Systemic lupus erythematosus (SLE is a multisystem autoimmune disorder in which complex genetic factors play an important role. Several strains of gene-targeted mice have been reported to develop SLE, implicating the null genes in the causation of disease. However, hybrid strains between 129 and C57BL/6 mice, widely used in the generation of gene-targeted mice, develop spontaneous autoimmunity. Furthermore, the genetic background markedly influences the autoimmune phenotype of SLE in gene-targeted mice. This suggests an important role in the expression of autoimmunity of as-yet-uncharacterised background genes originating from these parental mouse strains. Using genome-wide linkage analysis, we identified several susceptibility loci, derived from 129 and C57BL/6 mice, mapped in the lupus-prone hybrid (129 x C57BL/6 model. By creating a C57BL/6 congenic strain carrying a 129-derived Chromosome 1 segment, we found that this 129 interval was sufficient to mediate the loss of tolerance to nuclear antigens, which had previously been attributed to a disrupted gene. These results demonstrate important epistatic modifiers of autoimmunity in 129 and C57BL/6 mouse strains, widely used in gene targeting. These background gene influences may account for some, or even all, of the autoimmune traits described in some gene-targeted models of SLE.

  14. Celiac autoimmunity in autoimmune thyroid disease is highly prevalent with a questionable impact

    Directory of Open Access Journals (Sweden)

    Bharat Rakeshkumar Sharma


    Full Text Available Introduction: The prevalence of autoimmune thyroid disease (AITD is 10–12% in the general population worldwide. Among various disorders co-existing with AITD, the concomitance of celiac disease (CD with AITD results in poor absorption of thyroid medications and results in higher doses of the same. Institution of gluten-free diet (GFD in this cohort helps reduce medication doses. Aim: To screen patients with AITD for the presence of celiac autoimmunity (CA. Materials and Methods: A total of 280 consecutive patients with AITD attending the thyroid Out-patient Department of a tertiary care hospital were screened for the presence of tissue transglutaminase antibodies (immunoglobulin A tissue transglutaminase. Those with a positive titer (but < 10 times the upper limit of normal underwent upper gastrointestinal endoscopy and duodenal mucosal biopsy for the diagnosis of CD, followed by institution of GFD in confirmed cases. Results: Of a total of 280 (182 females and 98 males patients with AITD screened, 24 (8.6% turned out to be positive for CA. Of 24 (8.6%, 15 (8.24% females and 9 (9.18% males were positive for CA. There was no statistically significant difference in the thyroxine doses required for normalization of thyroid function and the weight of the patients in CA positive and CA negative patients. Conclusions: The prevalence of CD in patients with AITD is much greater than in the general population. This forms the basis for screening patients with AITD for presence of CD.

  15. Serum cytokine levels in autoimmune and non-autoimmune hyperthyroid states

    Directory of Open Access Journals (Sweden)

    L.S. Ward


    Full Text Available Although the role of interleukin-2 (IL-2 and interferon gamma (gIFN is still poorly understood in hyperthyroid diseases, it is reasonable to assume that these cytokines may be present at higher levels in Graves' disease (GD than in other primarily non-autoimmune thyroid diseases. In order to look for an easy method to distinguish GD from primarily non-autoimmune causes of hyperthyroidism, we compared 13 healthy individuals with 21 treated and untreated hyperthyroid GD patients and with 19 patients with hyperthyroidism due to other etiologies: 7 cases of multinodular goiter, 5 cases of excessive hormone replacement and 7 cases of amiodarone-associated hyperthyroidism. All patients presented low TSH levels and a dubious clinical thyroid state. We found a good correlation between TSH and serum IL-2 levels (r = 0.56; PgIFN (P<0.01 levels were lower in the hyperthyroid group of patients than in control subjects, suggesting a depressed TH1 pattern in the T-cell subset of hyperthyroid patients. GD had normal IL-2 levels, while patients with other forms of thyrotoxicosis presented decreased IL-2 levels (P<0.05. There was no difference between treated and untreated GD patients. We suggest that the direct measurement of serum IL-2 level may help to confirm hyperthyroidism caused by GD.

  16. An autonomous weeding robot for organic farming

    NARCIS (Netherlands)

    Bakker, T.; Asselt, van C.J.; Bontsema, J.; Müller, J.; Straten, van G.


    The objective of this research is the replacement of hand weeding in organic farming by a device working autonomously at ¯eld level. The autonomous weeding robot was designed using a structured design approach, giving a good overview of the total design. A vehicle was developed with a diesel engine,

  17. Autonomous Control of Space Reactor Systems

    International Nuclear Information System (INIS)

    Belle R. Upadhyaya; K. Zhao; S.R.P. Perillo; Xiaojia Xu; M.G. Na


    Autonomous and semi-autonomous control is a key element of space reactor design in order to meet the mission requirements of safety, reliability, survivability, and life expectancy. Interrestrial nuclear power plants, human operators are available to perform intelligent control functions that are necessary for both normal and abnormal operational conditions

  18. Overfeeding, autonomic regulation and metabolic consequences.

    NARCIS (Netherlands)

    Scheurink, A.J.W.; Balkan, B; Strubbe, J.H.; van Dijk, G.; Steffens, A.B

    The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The

  19. Technologies for highly miniaturized autonomous sensor networks

    NARCIS (Netherlands)

    Baert, K.; Gyselinckx, B.; Torfs, T.; Leonov, V.; Yazicioglu, F.; Brebels, S.; Donnay, S.; Vanfleteren, J.; Beyne, E.; Hoof, C. van


    Recent results of the autonomous sensor research program HUMAN++ will be summarized in this paper. The research program aims to achieve highly miniaturized and (nearly) autonomous sensor systems that assist our health and comfort. Although the application examples are dedicated to human

  20. Cooperative Control of Multiple Unmanned Autonomous Vehicles (United States)


    I I Final Report 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Cooperative Control of Multiple Unmanned Autonomous Vehicles F49620-01-1-0337 6. AUTHOR(S... Autonomous Vehicles Final Report Kendall E. Nygard Department of Computer Science and Operations Research North Dakota State University Fargo, ND 58105-5164

  1. 3-D Vision Techniques for Autonomous Vehicles (United States)


    TITLE (Include Security Classification) W 3-D Vision Techniques for Autonomous Vehicles 12 PERSONAL AUTHOR(S) Martial Hebert, Takeo Kanade, inso Kweoni... Autonomous Vehicles Martial Hebert, Takeo Kanade, Inso Kweon CMU-RI-TR-88-12 The Robotics Institute Carnegie Mellon University Acession For Pittsburgh

  2. Autonomy Level Specification for Intelligent Autonomous Vehicles (United States)


    Autonomy Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report Hui-Min Huang, Elena Messina, James Albus...Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

  3. Intelligent autonomous systems 12. Vol. 2. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sukhan [Sungkyunkwan Univ., Gyeonggi-Do (Korea, Republic of). College of Information and Communication Engineering; Yoon, Kwang-Joon [Konkuk Univ., Seoul (Korea, Republic of); Cho, Hyungsuck [Daegu Gyeongbuk Institute of Science and Technology, Daegu (Korea, Republic of); Lee, Jangmyung (eds.) [Pusan National Univ. (Korea, Republic of). Dept. of Electronics Engineering


    Recent research in Intelligent and Autonomous Systems. Volume 2 of the proceedings of the 12th International Conference IAS-12, held June 26-29, 2012, jeju Island, Korea. Written by leading experts in the field. Intelligent autonomous systems are emerged as a key enabler for the creation of a new paradigm of services to humankind, as seen by the recent advancement of autonomous cars licensed for driving in our streets, of unmanned aerial and underwater vehicles carrying out hazardous tasks on-site, and of space robots engaged in scientific as well as operational missions, to list only a few. This book aims at serving the researchers and practitioners in related fields with a timely dissemination of the recent progress on intelligent autonomous systems, based on a collection of papers presented at the 12th International Conference on Intelligent Autonomous Systems, held in Jeju, Korea, June 26-29, 2012. With the theme of ''Intelligence and Autonomy for the Service to Humankind, the conference has covered such diverse areas as autonomous ground, aerial, and underwater vehicles, intelligent transportation systems, personal/domestic service robots, professional service robots for surgery/rehabilitation, rescue/security and space applications, and intelligent autonomous systems for manufacturing and healthcare. This volume 2 includes contributions devoted to Service Robotics and Human-Robot Interaction and Autonomous Multi-Agent Systems and Life Engineering.

  4. Safe and Autonomous Drones for Urban Flight (United States)

    Krishnakumar, Kalmanje


    Autonomous vehicles are no longer futuristic technology; in fact, there are already cars with self-driving features on the road. Over the next five years, the connected vehicles will disrupt the entire automotive and UAS ecosystems. The industry will undergo fundamental change as semi-autonomous driving and flying emerges, followed by an eventual shift to full autonomy.

  5. Autonomous Control of Space Reactor Systems

    Energy Technology Data Exchange (ETDEWEB)

    Belle R. Upadhyaya; K. Zhao; S.R.P. Perillo; Xiaojia Xu; M.G. Na


    Autonomous and semi-autonomous control is a key element of space reactor design in order to meet the mission requirements of safety, reliability, survivability, and life expectancy. Interrestrial nuclear power plants, human operators are avilable to perform intelligent control functions that are necessary for both normal and abnormal operational conditions.

  6. Heat shock protein-derived T-cell epitopes contribute to autoimmune inflammation in pediatric Crohn's disease.

    Directory of Open Access Journals (Sweden)

    Gisella L Puga Yung

    Full Text Available Pediatric Crohn's disease is a chronic auto inflammatory bowel disorder affecting children under the age of 17 years. A putative etiopathogenesis of Crohn's disease (CD is associated with disregulation of immune response to antigens commonly present in the gut microenvironment. Heat shock proteins (HSP have been identified as ubiquitous antigens with the ability to modulate inflammatory responses associated with several autoimmune diseases. The present study tested the contribution of immune responses to HSP in the amplification of autoimmune inflammation in chronically inflamed mucosa of pediatric CD patients. Colonic biopsies obtained from normal and CD mucosa were stimulated with pairs of Pan HLA-DR binder HSP60-derived peptides (human/bacterial homologues. The modulation of RNA and protein levels of induced proinflammatory cytokines were measured. We identified two epitopes capable of sustaining proinflammatory responses, specifically TNF< and IFN induction, in the inflamed intestinal mucosa in CD patients. The responses correlated positively with clinical and histological measurements of disease activity, thus suggesting a contribution of immune responses to HSP in pediatric CD site-specific mucosal inflammation.

  7. Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity.

    Directory of Open Access Journals (Sweden)

    Gangduo Wang

    Full Text Available Exposure to trichloroethene (TCE, a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC supplementation provided protection by attenuating oxidative stress. This study was undertaken to further evaluate the contribution of nitrosative stress in TCE-mediated autoimmunity and to identify proteins susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ∼ 250 mg/kg/day via drinking water. TCE exposure led to significant increases in serum anti-nuclear and anti-histone antibodies together with significant induction of iNOS and increased formation of nitrotyrosine (NT in sera and livers. Proteomic analysis identified 14 additional nitrated proteins in the livers of TCE-treated mice. Furthermore, TCE exposure led to decreased GSH levels and increased activation of NF-κB. Remarkably, NAC supplementation not only ameliorated TCE-induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins, NF-κB p65 activation and increased GSH levels, but also the markers of autoimmunity, as evident from decreased levels of autoantibodies in the sera. These findings provide support to the role of nitrosative stress in TCE-mediated autoimmune response and identify specific nitrated proteins which could have autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for designing therapeutic strategies.

  8. Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity (United States)

    Rapoport, Basil


    Thyroid autoimmunity involves loss of tolerance to thyroid proteins in genetically susceptible individuals in association with environmental factors. In central tolerance, intrathymic autoantigen presentation deletes immature T cells with high affinity for autoantigen-derived peptides. Regulatory T cells provide an alternative mechanism to silence autoimmune T cells in the periphery. The TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual properties (“immunogenicity”) that contribute to breaking tolerance, including size, abundance, membrane association, glycosylation, and polymorphisms. Insight into loss of tolerance to thyroid proteins comes from spontaneous and induced animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and instead control the balance between Graves' disease and thyroiditis; 3) breaking TSHR tolerance involves contributions from major histocompatibility complex molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5) tolerance is induced by thyroid autoantigen administration before autoimmunity is established; 6) interferon-α therapy for hepatitis C infection enhances thyroid autoimmunity in patients with intact immunity; Graves' disease developing after T-cell depletion reflects reconstitution autoimmunity; and 7) most environmental factors (including excess iodine) “reveal,” but do not induce, thyroid autoimmunity. Micro-organisms likely exert their effects via bystander stimulation. Finally, no single mechanism explains the loss of tolerance to thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen

  9. P-glycoprotein in autoimmune rheumatic diseases. (United States)

    García-Carrasco, M; Mendoza-Pinto, C; Macias Díaz, S; Vera-Recabarren, M; Vázquez de Lara, L; Méndez Martínez, S; Soto-Santillán, P; González-Ramírez, R; Ruiz-Arguelles, A


    P-glycoprotein (Pgp) is a transmembrane protein of 170 kD encoded by the multidrug resistance 1 (MDR-1) gene, localized on chromosome 7. More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors. Polymorphisms that have a protective effect on the development of conditions such as Parkinson disease have also been identified. P-glycoprotein belongs to the adenosine triphosphate binding cassette transporter superfamily and its structure comprises a chain of approximately 1280 aminoacid residues with an N-C terminal structure, arranged as 2 homologous halves, each of which has 6 transmembrane segments, with a total of 12 segments with 2 cytoplasmic nucleotide binding domains. Many cytokines like interleukin 2 and tumor necrosis factor alpha increase Pgp expression and activity. Pgp functions as an efflux pump for a variety of toxins in order to protect particular organs and tissues as the central nervous system. Pgp transports a variety of substrates including glucocorticoids while other drugs such as tacrolimus and cyclosporine A act as modulators of this protein. The most widely used method to measure Pgp activity is flow cytometry using naturally fluorescent substrates such as anthracyclines or rhodamine 123. The study of drug resistance and its association to Pgp began with the study of resistance to chemotherapy in the treatment of cancer and antiretroviral therapy for human immunodeficiency virus; however, the role of Pgp in the treatment of systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis has been a focus of study lately and has emerged as an important mechanism by which treatment failure occurs. The present review analyzes the role of Pgp in these autoimmune diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Pregnancy and the risk of autoimmune disease.

    LENUS (Irish Health Repository)

    Khashan, Ali S


    Autoimmune diseases (AID) predominantly affect women of reproductive age. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. We investigated the effect of vaginal delivery, caesarean section (CS) and induced abortion on the risk of subsequent maternal AID. Using the Danish Civil Registration System (CRS) we identified women who were born between 1960 and 1992. We performed data linkage between the CRS other Danish national registers to identify women who had a pregnancy and those who developed AID. Women were categorised into 4 groups; nulligravida (control group), women who had 1st child by vaginal delivery, whose 1st delivery was by CS and who had abortions. Log-linear Poisson regression with person-years was used for data analysis adjusting for several potential confounders. There were 1,035,639 women aged >14 years and 25,570 developed AID: 43.4% nulligravida, 44.3% had their first pregnancy delivered vaginally, 7.6% CS and 4.1% abortions. The risk of AID was significantly higher in the 1st year after vaginal delivery (RR = 1.1[1.0, 1.2]) and CS (RR = 1.3[1.1, 1.5]) but significantly lower in the 1st year following abortion (RR = 0.7[0.6, 0.9]). These results suggest an association between pregnancy and the risk of subsequent maternal AID. Increased risks of AID after CS may be explained by amplified fetal cell traffic at delivery, while decreased risks after abortion may be due to the transfer of more primitive fetal stem cells. The increased risk of AID in the first year after delivery may also be related to greater testing during pregnancy.

  11. Incidence and Characteristics of Autoimmune Hepatitis. (United States)

    Jiménez-Rivera, Carolina; Ling, Simon C; Ahmed, Najma; Yap, Jason; Aglipay, Mary; Barrowman, Nick; Graitson, Samantha; Critch, Jeff; Rashid, Mohsin; Ng, Vicky L; Roberts, Eve A; Brill, Herbert; Dowhaniuk, Jenna K; Bruce, Garth; Bax, Kevin; Deneau, Mark; Guttman, Orlee R; Schreiber, Richard A; Martin, Steven; Alvarez, Fernando


    Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease of unknown etiology, with limited population-based estimates of pediatric incidence. We reported the incidence of pediatric AIH in Canada and described its clinical characteristics. We conducted a retrospective cohort study of patients aged <18 years diagnosed with AIH between 2000-2009 at all pediatric centers in Canada. A total of 159 children with AIH (60.3% female, 13.2% type 2 AIH) were identified. Annual incidence was 0.23 per 100000 children. Median age at presentation for type 1 was 12 years (interquartile range: 11-14) versus 10 years for type 2 (interquartile range: 4.5-13) (P = .03). Fatigue (58%), jaundice (54%), and abdominal pain (49%) were the most common presenting symptoms. Serum albumin (33 vs 38 g/L; P = .03) and platelet count (187 000 vs 249 000; P <.001) were significantly lower and the international normalized ratio (1.4 vs 1.2; P <.001) was higher in cirrhotic versus noncirrhotic patients. Initial treatment included corticosteroids (80%), azathioprine (32%), and/or cyclosporine (13%). Response to treatment at 1 year was complete in 90%, and partial in 3%. 3% of patients had no response, and 3% responded and later relapsed. Nine patients underwent liver transplantation, and 4 patients died at a mean follow-up of 4 years. AIH is uncommon in children and adolescents in Canada. Type 1 AIH was diagnosed 5.5 times more frequently than type 2 AIH. Most patients respond well to conventional therapy, diminishing the need for liver transplantation. Copyright © 2015 by the American Academy of Pediatrics.

  12. Glioblastoma as differential diagnosis of autoimmune encephalitis. (United States)

    Vogrig, Alberto; Joubert, Bastien; Ducray, Francois; Thomas, Laure; Izquierdo, Cristina; Decaestecker, Kévin; Martinaud, Olivier; Gerardin, Emmanuel; Grand, Sylvie; Honnorat, Jérome


    To identify the clinical and radiological features that should raise suspicion for the autoimmune encephalitis (AE)-like presentation of glioblastoma. This is an observational, retrospective case series of patients referred to the French National Reference Center on Paraneoplastic Neurological Diseases for suspected AE (possible, probable or definite, using the 2016 criteria) who later received a final diagnosis of glioblastoma according to 2016 WHO criteria. An extensive literature search was also conducted for similar existing cases. Between 2014 and 2016, 306 patients were referred to our center for suspected AE. Six of these patients (2%) later developed pathologically confirmed glioblastoma. Thirteen patients (9 male) were included for analysis (6 from the present series and 7 from the literature); median age was 63. Initially, a diagnosis of AE was clinically suspected based on: working memory deficits (77%), seizures (62%) (including status epilepticus in 23%), and psychiatric symptoms (46%). Initial brain MRI was not in favor of a typical glioblastoma pattern and showed bilateral (54%) or unilateral selective limbic involvement. Five patients exhibited initial slight contrast enhancement. A clear inflammatory CSF was present in five patients and three from the literature showed autoantibody positivity (NMDAR, VGKC, GluRepsilon2). Median delay between suspicions of AE to GBM diagnosis was 3 months (range 1.5-24) and one patient from the literature was diagnosed post-mortem. An alternative diagnosis of glioblastoma should be considered in patients presenting initially as AE, especially in patients who do not fulfill the criteria for definite AE and in those with a poor clinical evolution despite initial improvement.

  13. Autoimmune hemolytic anemia: From lab to bedside

    Directory of Open Access Journals (Sweden)

    R K Chaudhary


    Full Text Available Autoimmune hemolytic anemia (AIHA is not an uncommon clinical disorder and requires advanced, efficient immunohematological and transfusion support. Many AIHA patients have underlying disorder and therefore, it is incumbent upon the clinician to investigate these patients in detail, as the underlying condition can be of a serious nature such as lymphoproliferative disorder or connective tissue disorder. Despite advances in transfusion medicine, simple immunohematological test such as direct antiglobulin test (DAT still remains the diagnostic hallmark of AIHA. The sensitive gel technology has enabled the immunohematologist not only to diagnose serologically such patients, but also to characterize red cell bound autoantibodies with regard to their class, subclass and titer in a rapid and simplified way. Detailed characterization of autoantibodies is important, as there is a relationship between in vivo hemolysis and strength of DAT; red cell bound multiple immunoglobulins, immunoglobulin G subclass and titer. Transfusing AIHA patient is a challenge to the immunohematologist as it is encountered with difficulties in ABO grouping and cross matching requiring specialized serological tests such as alloadsorption or autoadsorption. At times, it may be almost impossible to find a fully matched unit to transfuse these patients. However, transfusion should not be withheld in a critically ill patient even in the absence of compatible blood. The "best match" or "least incompatible units" can be transfused to such patients under close supervision without any serious side-effects. All blood banks should have the facilities to perform the necessary investigations required to issue "best match" packed red blood cells in AIHA. Specialized techniques such as elution and adsorption, which at times are helpful in enhancing blood safety in AIHA should be established in all transfusion services.

  14. Metabotropic glutamate receptor type 1 autoimmunity (United States)

    Lopez-Chiriboga, A. Sebastian; Komorowski, Lars; Kümpfel, Tania; Probst, Christian; Hinson, Shannon R.; Pittock, Sean J.


    Objective: To describe retrospectively the clinical associations of immunoglobulin G (IgG) targeting metabotropic glutamate receptor 1 (mGluR1-IgG). Methods: Specimens of 9 patients evaluated on a service basis in the Mayo Clinic Neuroimmunology Laboratory by tissue-based immunofluorescence assay (IFA) yielded a robust, synaptic immunostaining pattern consistent with mGluR1-IgG (serum, 9; CSF, 2 available). Transfected HEK293 cell-based assay (CBA) confirmed mGluR1 specificity in all 11 specimens. A further 2 patients were detected in Germany primarily by CBA. Results: The median symptom onset age for the 11 patients was 58 years (range 33–81 years); 6 were male. All 9 Mayo Clinic patients had subacute onset of cerebellar ataxia, 4 had dysgeusia, 1 had psychiatric symptoms, and 1 had cognitive impairment. All were evaluated for malignancy, but only 1 was affected (cutaneous T-cell lymphoma). One developed ataxia post–herpes zoster infection. Head MRIs were generally atrophic or normal-appearing, and CSF was inflammatory in just 1 of 5 tested, though mGluR1-IgG was detected in both specimens submitted. Five patients improved (attributable to immunotherapy in 4, spontaneously in 1), 3 stabilized (attributable to immunotherapy in 2, cancer therapy in 1), and 1 progressively declined (untreated). The 2 German patients had ataxia, but fulfilled multiple sclerosis diagnostic criteria (1 relapsing-remitting, 1 progressive). However, both had histories of hematologic malignancy (acute lymphocytic leukemia and mantle cell lymphoma), and had mGluR1-IgG detected in serum by CBA (weakly positive on tissue-based IFA). Conclusions: mGluR1 autoimmunity represents a treatable form of cerebellar ataxia. Dysgeusia may be a diagnostic clue. Paraneoplastic, parainfectious, or idiopathic causes may occur. PMID:26888994

  15. ROV90 - A prototype autonomous inspection vehicle

    Energy Technology Data Exchange (ETDEWEB)

    Roedseth, Oe.J.; Hallset, J.O.


    Simple autonomous inspection vehicles are suitable for operations where the cost, danger to humans, or area of operation prohibits the use of conventional underwater technology. Autonomous vehicles are, however, in their infancy and few such vehicles are available. There are still some problems to be overcome before this technology becomes useful in commercial applications. We have built ROV90 to investigate these problems. It is a test bed for experimenting with the different parts of an autonomous underwater vehicle. ROV90 will be able to autonomously follow prominent features in the real world, man made or natural. Examples are pipelines or walls in tunnels. ROV90 is tethered, but we are planning to use experience and results from ROV90 to develop av ''real'' autonomous underwater vehicle (AUV) called PISCIS. 11 refs., 8 figs.

  16. Current challenges in autonomous driving (United States)

    Barabás, I.; Todoruţ, A.; Cordoş, N.; Molea, A.


    Nowadays the automotive industry makes a quantum shift to a future, where the driver will have smaller and smaller role in driving his or her vehicle ending up being totally excluded. In this paper, we have investigated the different levels of driving automatization, the prospective effects of these new technologies on the environment and traffic safety, the importance of regulations and their current state, the moral aspects of introducing these technologies and the possible scenarios of deploying the autonomous vehicles. We have found that the self-driving technologies are facing many challenges: a) They must make decisions faster in very diverse conditions which can include many moral dilemmas as well; b) They have an important potential in reducing the environmental pollution by optimizing their routes, driving styles by communicating with other vehicles, infrastructures and their environment; c) There is a considerable gap between the self-drive technology level and the current regulations; fortunately, this gap shows a continuously decreasing trend; d) In case of many types of imminent accidents management there are many concerns about the ability of making the right decision. Considering that this field has an extraordinary speed of development, our study is up to date at the submission deadline. Self-driving technologies become increasingly sophisticated and technically accessible, and in some cases, they can be deployed for commercial vehicles as well. According to the current stage of research and development, it is still unclear how the self-driving technologies will be able to handle extreme and unexpected events including their moral aspects. Since most of the traffic accidents are caused by human error or omission, it is expected that the emergence of the autonomous technologies will reduce these accidents in their number and gravity, but the very few currently available test results have not been able to scientifically underpin this issue yet. The

  17. Autonomic Function in Neurodegenerative Diseases

    DEFF Research Database (Denmark)

    Sørensen, Gertrud Laura; Jennum, Poul Jørgen


    areas, which is consistent with the Braak hypothesis. In the narcolepsy patients, it was shown that a reduced HRR to arousals was primarily predicted by hypocretin deficiency in both rapid-eye-movement (REM) and non-REM sleep, independent of cataplexy and other factors. The results confirm...... that hypocretin deficiency affects the autonomic nervous system of patients with narcolepsy and that the hypocretin system is important for proper heart rate modulation at rest.Furthermore, it was shown that hypocretin deficiency and cataplexy are associated with signs of destabilized sleep-wake and REM sleep...... control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches. The increased frequency of transitions may cause increased sympathetic activity during sleep and thereby increased heart rate, or the increased heart rate could be caused by decreased...

  18. Autonomous navigation system and method (United States)

    Bruemmer, David J [Idaho Falls, ID; Few, Douglas A [Idaho Falls, ID


    A robot platform includes perceptors, locomotors, and a system controller, which executes instructions for autonomously navigating a robot. The instructions repeat, on each iteration through an event timing loop, the acts of defining an event horizon based on the robot's current velocity, detecting a range to obstacles around the robot, testing for an event horizon intrusion by determining if any range to the obstacles is within the event horizon, and adjusting rotational and translational velocity of the robot accordingly. If the event horizon intrusion occurs, rotational velocity is modified by a proportion of the current rotational velocity reduced by a proportion of the range to the nearest obstacle and translational velocity is modified by a proportion of the range to the nearest obstacle. If no event horizon intrusion occurs, translational velocity is set as a ratio of a speed factor relative to a maximum speed.

  19. Design of Autonomous Underwater Vehicle

    Directory of Open Access Journals (Sweden)

    Tadahiro Hyakudome


    Full Text Available There are concerns about the impact that global warming will have on our environment, and which will inevitably result in expanding deserts and rising water levels. While a lot of underwater vehicles are utilized, AUVs (Autonomous Underwater Vehicle were considered and chosen, as the most suitable tool for conduction survey concerning these global environmental problems. AUVs can comprehensive survey because the vehicle does not have to be connected to the support vessel by tether cable. When such underwater vehicles are made, it is necessary to consider about the following things. 1 Seawater and Water Pressure Environment, 2 Sink, 3 There are no Gas or Battery Charge Stations, 4 Global Positioning System cannot use, 5 Radio waves cannot use. In the paper, outline of above and how deal about it are explained.

  20. Wireless autonomous device data transmission (United States)

    Sammel, Jr., David W. (Inventor); Cain, James T. (Inventor); Mickle, Marlin H. (Inventor); Mi, Minhong (Inventor)


    A method of communicating information from a wireless autonomous device (WAD) to a base station. The WAD has a data element having a predetermined profile having a total number of sequenced possible data element combinations. The method includes receiving at the WAD an RF profile transmitted by the base station that includes a triggering portion having a number of pulses, wherein the number is at least equal to the total number of possible data element combinations. The method further includes keeping a count of received pulses and wirelessly transmitting a piece of data, preferably one bit, to the base station when the count reaches a value equal to the stored data element's particular number in the sequence. Finally, the method includes receiving the piece of data at the base station and using the receipt thereof to determine which of the possible data element combinations the stored data element is.

  1. Autonomous Infrastructure for Observatory Operations (United States)

    Seaman, R.

    This is an era of rapid change from ancient human-mediated modes of astronomical practice to a vision of ever larger time domain surveys, ever bigger "big data", to increasing numbers of robotic telescopes and astronomical automation on every mountaintop. Over the past decades, facets of a new autonomous astronomical toolkit have been prototyped and deployed in support of numerous space missions. Remote and queue observing modes have gained significant market share on the ground. Archives and data-mining are becoming ubiquitous; astroinformatic techniques and virtual observatory standards and protocols are areas of active development. Astronomers and engineers, planetary and solar scientists, and researchers from communities as diverse as particle physics and exobiology are collaborating on a vast range of "multi-messenger" science. What then is missing?

  2. Digital autonomous terminal access communications (United States)

    Novacki, S.


    A significant problem for the Bus Monitor Unit is to identify the source of a given transmission. This problem arises from the fact that the label which identifies the source of the transmission as it is put into the bus is intercepted by the Digital Autonomous Terminal Access Communications (DATAC) terminal and removed from the transmission. Thus, a given subsystem will see only data associated with a label and never the identifying label itself. The Bus Monitor must identify the source of the transmission so as to be able to provide some type of error identification/location in the event that some problem with the data transmission occurs. Steps taken to alleviate this problem by modifications to the DATAC terminal are discussed.

  3. Full autonomous microline trace robot (United States)

    Yi, Deer; Lu, Si; Yan, Yingbai; Jin, Guofan


    Optoelectric inspection may find applications in robotic system. In micro robotic system, smaller optoelectric inspection system is preferred. However, as miniaturizing the size of the robot, the number of the optoelectric detector becomes lack. And lack of the information makes the micro robot difficult to acquire its status. In our lab, a micro line trace robot has been designed, which autonomous acts based on its optoelectric detection. It has been programmed to follow a black line printed on the white colored ground. Besides the optoelectric inspection, logical algorithm in the microprocessor is also important. In this paper, we propose a simply logical algorithm to realize robot's intelligence. The robot's intelligence is based on a AT89C2051 microcontroller which controls its movement. The technical details of the micro robot are as follow: dimension: 30mm*25mm*35*mm; velocity: 60mm/s.

  4. Autoimmunity in Wiskott-Aldrich Syndrome: an unsolved enigma

    Directory of Open Access Journals (Sweden)

    Marco eCatucci


    Full Text Available Wiskott-Aldrich Syndrome (WAS is a severe X-linked Primary Immunodeficiency (PID that affects 1 to 10 out of 1 million male individuals. WAS is caused by mutations in the WAS Protein (WASP expressing gene that leads to the absent or reduced expression of the protein. WASP is a cytoplasmic protein that regulates the formation of actin filaments in hematopoietic cells. WASP deficiency causes many immune cell defects both in humans and in the WAS murine model, the Was-/- mouse. Both cellular and humoral immune defects in WAS patients contribute to the onset of severe clinical manifestations, in particular microthrombocytopenia, eczema, recurrent infections and a high susceptibility to develop autoimmunity and malignancies. Autoimmune diseases affect from 22% to 72% of WAS patients and the most common manifestation is autoimmune hemolytic anemia, followed by vasculitis, arthritis, neutropenia, inflammatory bowel disease and IgA nephropathy. Many groups have widely explored immune cell functionality in WAS partially explaining how cellular defects may lead to pathology. However, the mechanisms underlying the occurrence of autoimmune manifestations have not been clearly described yet. In the present review, we report the most recent progresses in the study of immune cell function in WAS that have started to unveil the mechanisms contributing to autoimmune complications in WAS patients.

  5. DNA-abzymes in autoimmune diseases in clinic and experiment

    Directory of Open Access Journals (Sweden)

    T E Naumova


    Full Text Available DNA-abzymes enzymes in autoimmune diseases in clinic and experiment T.E. Naumova, O.M. Durova, A.G. Gabibov, Z.S. Alekberova, S. V. Suchkov DNA-hydrolyzing autoantibodies (AAB or DNA-abzymes can be found in autoimmune diseases in clinic and experiment. Technology of serum express screening for presence of DNA abzymes is described. Comparative study of DNA-hydrolising activity in patients with different forms of systemic and organ-specific autoimmune diseases was performed. Blood of clinically healthy donors was usually free of IgG DNA-abzymes. DNA-abzymes were most often revealed in patients with systemic lupus erythematosus (SLE and rheumatoid arthritis (RA less often in patients with organ-specific forms of autoimmune disturbances. The results of the study confirm the hypothesis of autoimmune origin of IgG DNA abzymes and demonstrate the possibility to use them in clinical practice for monitoring to disease activity in SLE and RA.

  6. MHC class II polymorphisms, autoreactive T-cells and autoimmunity

    Directory of Open Access Journals (Sweden)

    Sue eTsai


    Full Text Available Major histocompatibility complex (MHC genes, also known as human leukocyte antigen genes (HLA in humans, are the prevailing contributors of genetic susceptibility to autoimmune diseases such as Type 1 Diabetes (T1D, Multiple Sclerosis (MS, and Rheumatoid arthritis (RA, among others (Todd and Wicker, 2001;MacKay et al., 2002;Hafler et al., 2007. Although the pathways through which MHC molecules afford autoimmune risk or resistance remain to be fully mapped out, it is generally accepted that they do so by shaping the central and peripheral T cell repertoires of the host towards autoimmune proclivity or resistance, respectively. Disease-predisposing MHC alleles would both spare autoreactive thymocytes from central tolerance and bias their development towards a pathogenic phenotype. Protective MHC alleles, on the other hand, would promote central deletion of autoreactive thymocytes and skew their development towards non-pathogenic phenotypes. This interpretation of the data is at odds with two other observations: that in MHC-heterozygous individuals, resistance is dominant over susceptibility; and that it is difficult to understand how deletion of one or a few clonal autoreactive T cell types would suffice to curb autoimmune responses driven by hundreds if not thousands of autoreactive T cell specificities. This review provides an update on current advances in our understanding of the mechanisms underlying MHC class II-associated autoimmune disease susceptibility and/or resistance and attempts to reconcile these seemingly opposing concepts.

  7. Assessment of Gastric Emptying in Patients with Autoimmune Gastritis. (United States)

    Kalkan, Çağdaş; Soykan, Irfan; Soydal, Çiğdem; Özkan, Elgin; Kalkan, Emra


    Symptoms of patients with autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any delay in gastric emptying of solid food exists in patients with autoimmune gastritis and, if so, to identify the factors that might affect delayed gastric emptying. A total of 165 patients (106 women) diagnosed as having autoimmune gastritis were analyzed by means of a gastric emptying test. All patients underwent a standardized scintigraphic gastric emptying study. Patients with delayed gastric emptying and normal gastric emptying tests were then compared by means of factors that might affect gastric emptying. Also 65 patients with functional dyspepsia who had a gastric emptying study constituted the control group. The median gastric emptying T ½ time was 127.43 min (min-max 50-953) for patients with AIG and 81 min (min-max 21-121.6) for functional dyspepsia patients (p gastritis, gastric emptying is generally delayed. Autoimmune gastritis is an important etiology to explain the finding of delayed gastric emptying on a radionuclide test. This new finding is likely to be relevant to clinicians when evaluating and initiating appropriate medical treatment for patients with autoimmune gastritis manifesting upper gastrointestinal symptoms.

  8. Autoimmunity/inflammation in a monogenic primary immunodeficiency cohort. (United States)

    Rae, William; Ward, Daniel; Mattocks, Christopher J; Gao, Yifang; Pengelly, Reuben J; Patel, Sanjay V; Ennis, Sarah; Faust, Saul N; Williams, Anthony P


    Primary immunodeficiencies (PIDs) are rare inborn errors of immunity that have a heterogeneous phenotype that can include severe susceptibility to life-threatening infections from multiple pathogens, unique sensitivity to a single pathogen, autoimmune/inflammatory (AI/I) disease, allergies and/or malignancy. We present a diverse cohort of monogenic PID patients with and without AI/I diseases who underwent clinical, genetic and immunological phenotyping. Novel pathogenic variants were identified in IKBKG , CTLA4 , NFKB1 , GATA2 , CD40LG and TAZ as well as previously reported pathogenic variants in STAT3 , PIK3CD , STAT1 , NFKB2 and STXBP2 . AI/I manifestations were frequently encountered in PIDs, including at presentation. Autoimmunity/inflammation was multisystem in those effected, and regulatory T cell (Treg) percentages were significantly decreased compared with those without AI/I manifestations. Prednisolone was used as the first-line immunosuppressive agent in all cases, however steroid monotherapy failed long-term control of autoimmunity/inflammation in the majority of cases and additional immunosuppression was required. Patients with multisystem autoimmunity/inflammation should be investigated for an underlying PID, and in those with PID early assessment of Tregs may help to assess the risk of autoimmunity/inflammation.

  9. Autoimmunity-Basics and link with periodontal disease. (United States)

    Kaur, Gagandeep; Mohindra, Kanika; Singla, Shifali


    Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Periodontal diseases are characterized by inflammatory conditions that directly affect teeth-supporting structures, which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidence of involvement of immunopathology has been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T-cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes

    International Nuclear Information System (INIS)

    Yang Zandong; Chen Meng; Carter, Jeffrey D.; Nunemaker, Craig S.; Garmey, James C.; Kimble, Sarah D.; Nadler, Jerry L.


    Type 1 diabetes mellitus (T1DM) is an autoimmune disease leading to near complete pancreatic β-cell destruction. New evidence suggests that β-cell regeneration is possible, but ongoing autoimmune damage prevents restoration of β-cell mass. We tested the hypothesis that simultaneously blocking autoimmune cytokine damage and supplying a growth-promoting stimulus for β-cells would provide a novel approach to reverse T1DM. Therefore, in this study we combined lisofylline to suppress autoimmunity and exendin-4 to enhance β-cell proliferation for treating autoimmune-mediated diabetes in the non-obese diabetic (NOD) mouse model. We found that this combined therapy effectively reversed new-onset diabetes within a week of therapy, and even maintained euglycemia up to 145 days after treatment withdrawal. The therapeutic effect of this regimen was associated with improved β-cell metabolism and insulin secretion, while reducing β-cell apoptosis. It is possible that such combined therapy could become a new strategy to defeat T1DM in humans

  11. Understanding mechanisms of autoimmunity through translational research in vitiligo (United States)

    Strassner, James P; Harris, John E


    Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible. PMID:27764715

  12. Roles of T Cells in the Pathogenesis of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Dinglei Su


    Full Text Available γδ T cells are a minor population of T cells that express the TCR γδ chains, mainly distributed in the mucosal and epithelial tissue and accounting for less than 5% of the total T cells in the peripheral blood. By bridging innate and adaptive immunity, γδ T cells play important roles in the anti-infection, antitumor, and autoimmune responses. Previous research on γδ T cells was primarily concentrated on infectious diseases and tumors, whereas their functions in autoimmune diseases attracted much attention. In this paper, we summarized the various functions of γδ T cells in two prototypical autoimmune connective tissue diseases, that is, SLE and RA, elaborating on their antigen-presenting capacity, secretion of proinflammatory cytokines, immunomodulatory effects, and auxiliary function for B cells, which contribute to overproduction of proinflammatory cytokines and pathogenic autoantibodies, ultimately leading to the onset of these autoimmune diseases. Elucidation of the roles of γδ T cells in autoimmune diseases is not only conducive to in-depth understanding of the pathogenesis of these diseases, but also beneficial in providing theoretical support for the development of γδ T-cell-targeted therapy.

  13. Autoimmunity, environmental exposure and vaccination: is there a link?

    International Nuclear Information System (INIS)

    Ravel, G.; Christ, M.; Horand, F.; Descotes, J.


    Although the wide clinical experience shows that vaccines are generally safe, concern has been expressed for a causal link between vaccines and autoimmune diseases. Even though the mechanisms of autoimmunity are ill-elucidated, the role of pre-existing risk factors including genetic predisposition and environmental factors is largely accepted. The present study was undertaken to test the hypothesis that vaccines can promote autoimmunity in genetically-prone individuals when simultaneously exposed to a chemical known to induce autoimmune reactions. Female lupus-prone (NZBxNZW) F 1 mice were given 1 μg or 10 μg of a hepatitis B vaccine at 2-week intervals in conjunction with 40 μg of mercuric chloride three times per week for 6 weeks. A marked increase in serum IgG levels and a slight increase in anti-nuclear autoantibody (ANA) levels were seen in the mice given 10 μg of the vaccine plus mercuric chloride. No straightforward conclusion can be drawn from these results because of the extreme experimental conditions of this study. Nevertheless, the results tend to support the hypothesis that vaccination could enhance the risk of autoimmunity in genetically susceptible individuals when exposed to certain environmental chemicals

  14. Zinc and glutamate dehydrogenase in putative glutamatergic brain structures. (United States)

    Wolf, G; Schmidt, W


    A certain topographic parallelism between the distribution of histochemically (TIMM staining) identified zinc and putative glutamatergic structures in the rat brain was demonstrated. Glutamate dehydrogenase as a zinc containing protein is in consideration to be an enzyme synthesizing transmitter glutamate. In a low concentration range externally added zinc ions (10(-9) to 10(-7) M) induced an increase in the activity of glutamate dehydrogenase (GDH) originating from rat hippocampal formation, neocortex, and cerebellum up to 142.4%. With rising molarity of Zn(II) in the incubation medium, the enzyme of hippocampal formation and cerebellum showed a biphasic course of activation. Zinc ions of a concentration higher than 10(-6) M caused a strong inhibition of GDH. The effect of Zn(II) on GDH originating from spinal ganglia and liver led only to a decrease of enzyme activity. These results are discussed in connection with a functional correlation between zinc and putatively glutamatergic system.

  15. Autoimmunity in Arabidopsis acd11 is mediated by epigenetic regulation of an immune receptor.

    Directory of Open Access Journals (Sweden)

    Kristoffer Palma

    Full Text Available Certain pathogens deliver effectors into plant cells to modify host protein targets and thereby suppress immunity. These target modifications can be detected by intracellular immune receptors, or Resistance (R proteins, that trigger strong immune responses including localized host cell death. The accelerated cell death 11 (acd11 "lesion mimic" mutant of Arabidopsis thaliana exhibits autoimmune phenotypes such as constitutive defense responses and cell death without pathogen perception. ACD11 encodes a putative sphingosine transfer protein, but its precise role during these processes is unknown. In a screen for lazarus (laz mutants that suppress acd11 death we identified two genes, LAZ2 and LAZ5. LAZ2 encodes the histone lysine methyltransferase SDG8, previously shown to epigenetically regulate flowering time via modification of histone 3 (H3. LAZ5 encodes an RPS4-like R-protein, defined by several dominant negative alleles. Microarray and chromatin immunoprecipitation analyses showed that LAZ2/SDG8 is required for LAZ5 expression and H3 lysine 36 trimethylation at LAZ5 chromatin to maintain a transcriptionally active state. We hypothesize that LAZ5 triggers cell death in the absence of ACD11, and that cell death in other lesion mimic mutants may also be caused by inappropriate activation of R genes. Moreover, SDG8 is required for basal and R protein-mediated pathogen resistance in Arabidopsis, revealing the importance of chromatin remodeling as a key process in plant innate immunity.

  16. Supplementary data: Variation in the PTEN-induced putative kinase ...

    Indian Academy of Sciences (India)

    Variation in the PTEN-induced putative kinase 1 gene associated with the increase risk of type 2 diabetes in northern Chinese. Yanchun Qu, Liang Sun, Ze Yang and Ruifa Han. J. Genet. 90, 125–128. Table 1. Clinical characteristics of cases and controls. Phenotype. T2DM. Controls. P value. Age (years). 49.5 ± 11.1. 50.4 ± ...

  17. Interrelation specific autoimmune pathologies of a thyroid gland with inorganic autoimmune rheumatic diseases

    Directory of Open Access Journals (Sweden)

    O V Paramonova


    Full Text Available The problem of a pathology of a thyroid gland at rheumatic diseases, in particular at rheumatoid arthritis, remains actual and to this day. The work purpose was studying antitelogenesis to thyroid hormones at patients with mixt autoimmune pathology. In whey of blood of patients with RA and autothyroid pathology are found out antibodies (AB to Т3 and Т4, their concentration correlates with activity of pathological process. It is shown, that level AB to Т3 and Т4 authentically differs from the maintenance of the given antibodies in whey of blood of healthy faces. Level of antibodies to thyroid hormones can be considered as the criterion predicting development of pathology of a thyroid gland at patients with RA.

  18. Current challenges in autonomous vehicle development (United States)

    Connelly, J.; Hong, W. S.; Mahoney, R. B., Jr.; Sparrow, D. A.


    The field of autonomous vehicles is a rapidly growing one, with significant interest from both government and industry sectors. Autonomous vehicles represent the intersection of artificial intelligence (AI) and robotics, combining decision-making with real-time control. Autonomous vehicles are desired for use in search and rescue, urban reconnaissance, mine detonation, supply convoys, and more. The general adage is to use robots for anything dull, dirty, dangerous or dumb. While a great deal of research has been done on autonomous systems, there are only a handful of fielded examples incorporating machine autonomy beyond the level of teleoperation, especially in outdoor/complex environments. In an attempt to assess and understand the current state of the art in autonomous vehicle development, a few areas where unsolved problems remain became clear. This paper outlines those areas and provides suggestions for the focus of science and technology research. The first step in evaluating the current state of autonomous vehicle development was to develop a definition of autonomy. A number of autonomy level classification systems were reviewed. The resulting working definitions and classification schemes used by the authors are summarized in the opening sections of the paper. The remainder of the report discusses current approaches and challenges in decision-making and real-time control for autonomous vehicles. Suggested research focus areas for near-, mid-, and long-term development are also presented.

  19. Toll-Like Receptors in the Pathogenesis of Autoimmune Diseases (United States)

    Mohammad Hosseini, Akbar; Majidi, Jafar; Baradaran, Behzad; Yousefi, Mehdi


    Human Toll-like receptors (TLRs) are a family of transmembrane receptors, which play a key role in both innate and adaptive immune responses. Beside of recognizing specific molecular patterns that associated with different types of pathogens, TLRs may also detect a number of self-proteins and endogenous nucleic acids. Activating TLRs lead to the heightened expression of various inflammatory genes, which have a protective role against infection. Data rising predominantly from human patients and animal models of autoimmune disease indicate that, inappropriate triggering of TLR pathways by exogenous or endogenous ligands may cause the initiation and/or perpetuation of autoimmune reactions and tissue damage. Given their important role in infectious and non-infectious disease process, TLRs and its signaling pathways emerge as appealing targets for therapeutics. In this review, we demonstrate how TLRs pathways could be involved in autoimmune disorders and their therapeutic application. PMID:26793605

  20. Autoimmune pancreatitis: case series and review of the literature. (United States)

    Shakov, Rada; DePasquale, Joseph R; Elfarra, Hossam; Spira, Robert S


    Autoimmune pancreatitis (AuP) is a chronic pancreatic inflammation secondary to an underlying autoimmune mechanism. After early reports of a particular type of pancreatitis associated with hypergammaglobulinemia, others asserted that there is an autoimmune mechanism involved in some patients with chronic pancreatitis. In 1995 AuP was first described as a distinct clinical entity. Since then, there have been many documented cases of AuP in Japan, and now, perhaps due to increased awareness, more cases are being reported in Europe and the United States. Herein we present our experience with 3 cases of AuP and we review the relevant literature. These 3 cases demonstrate the difficulties that exist in making the diagnosis of AuP and the impact that the diagnosis can have on patient management.

  1. Autoimmune Progesterone Dermatitis Presenting as Stevens-Johnson Syndrome. (United States)

    Drayer, Sara M; Laufer, Larry R; Farrell, Maureen E


    Autoimmune progesterone dermatitis is an uncommon disease presenting with cyclical skin eruptions corresponding with the menstrual cycle luteal phase. Because symptoms are precipitated by rising progesterone levels, treatment relies on hormone suppression. A 22-year-old nulligravid woman presented with symptoms mistaken for Stevens-Johnson syndrome. A cyclic recurrence of her symptoms was noted, and the diagnosis of autoimmune progesterone dermatitis was made by an intradermal progesterone challenge. After 48 months, she remained refractory to medical management and definitive surgical treatment with bilateral oophorectomy was performed. Autoimmune progesterone dermatitis is a challenging diagnosis owing to its rarity and variety of clinical presentations. Treatment centers on suppression of endogenous progesterone and avoidance of exogenous triggers. When these modalities fail, surgical management must be undertaken.

  2. Autoimmune Addison's disease - An update on pathogenesis. (United States)

    Hellesen, Alexander; Bratland, Eirik; Husebye, Eystein S


    Autoimmunity against the adrenal cortex is the leading cause of Addison's disease in industrialized countries, with prevalence estimates ranging from 93-220 per million in Europe. The immune-mediated attack on adrenocortical cells cripples their ability to synthesize vital steroid hormones and necessitates life-long hormone replacement therapy. The autoimmune disease etiology is multifactorial involving variants in immune genes and environmental factors. Recently, we have come to appreciate that the adrenocortical cell itself is an active player in the autoimmune process. Here we summarize the complex interplay between the immune system and the adrenal cortex and highlight unanswered questions and gaps in our current understanding of the disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  3. Nuclear Factor-kappaB in Autoimmunity: Man and Mouse. (United States)

    Miraghazadeh, Bahar; Cook, Matthew C


    NF-κB (nuclear factor-kappa B) is a transcription complex crucial for host defense mediated by innate and adaptive immunity, where canonical NF-κB signaling, mediated by nuclear translocation of RelA, c-Rel, and p50, is important for immune cell activation, differentiation, and survival. Non-canonical signaling mediated by nuclear translocation of p52 and RelB contributes to lymphocyte maturation and survival and is also crucial for lymphoid organogenesis. We outline NF-κB signaling and regulation, then summarize important molecular contributions of NF-κB to mechanisms of self-tolerance. We relate these mechanisms to autoimmune phenotypes described in what is now a substantial catalog of immune defects conferred by mutations in NF-κB pathways in mouse models. Finally, we describe Mendelian autoimmune syndromes arising from human NF-κB mutations, and speculate on implications for understanding sporadic autoimmune disease.

  4. Autoimmune Diabetes and Thyroiditis Complicating Treatment with Nivolumab

    Directory of Open Access Journals (Sweden)

    Li Li


    Full Text Available Programmed cell death-1 (PD-1 ligand inhibitors have gained popularity in the treatment of advanced non-small-cell lung cancer. The immune system is regulated by stimulatory and inhibitory signaling and aims to achieve the balance between activation and inhibition. Treatment with immune checkpoint inhibitors enhances immune response, but is also known to diminish immune tolerance and increase autoimmune toxicity. Here we present a case of a patient with advanced squamous cell lung cancer who developed type I diabetes and thyroiditis after treatment with PD-1 checkpoint inhibitor nivolumab. The presence of autoimmune diabetes mellitus and thyroiditis were confirmed by markedly elevated titers of the glutamic acid decarboxylase autoantibody and thyroid peroxidase antibody, respectively. This report serves to heighten awareness of potential autoimmune toxicities related to anti-PD-1 therapy, especially as these toxicities are manageable if identified in a timely manner.

  5. Innate lymphoid cells in autoimmunity and chronic inflammatory diseases. (United States)

    Xiong, Tingting; Turner, Jan-Eric


    Abnormal activation of the innate immune system is a common feature of autoimmune and chronic inflammatory diseases. Since their identification as a separate family of leukocytes, innate lymphoid cells (ILCs) have emerged as important effector cells of the innate immune system. Alterations in ILC function and subtype distribution have been observed in a variety of immune-mediated diseases in humans and evidence from experimental models suggests a subtype specific role of ILCs in the pathophysiology of autoimmune inflammation. In this review, we discuss recent advances in the understanding of ILC biology in autoimmune and chronic inflammatory disorders, including multiple sclerosis, inflammatory bowel diseases, psoriasis, and rheumatic diseases, with a special focus on the potential of ILCs as therapeutic targets for the development of novel treatment strategies in humans.

  6. Pivotal Roles of GM-CSF in Autoimmunity and Inflammation (United States)

    Shiomi, Aoi; Usui, Takashi


    Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor, which stimulates the proliferation of granulocytes and macrophages from bone marrow precursor cells. In autoimmune and inflammatory diseases, Th17 cells have been considered as strong inducers of tissue inflammation. However, recent evidence indicates that GM-CSF has prominent proinflammatory functions and that this growth factor (not IL-17) is critical for the pathogenicity of CD4+ T cells. Therefore, the mechanism of GM-CSF-producing CD4+ T cell differentiation and the role of GM-CSF in the development of autoimmune and inflammatory diseases are gaining increasing attention. This review summarizes the latest knowledge of GM-CSF and its relationship with autoimmune and inflammatory diseases. The potential therapies targeting GM-CSF as well as their possible side effects have also been addressed in this review. PMID:25838639

  7. Palivizumab Exposure and the Risk of Autoimmune Disease

    DEFF Research Database (Denmark)

    Haerskjold, Ann; Linder, Marie; Henriksen, Lonny


    of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac......BACKGROUND: Treatment with biologic pharmaceuticals may be associated with an increased risk of immune-mediated disease. Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus infection. Palivizumab is primarily used in preterm...... children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated. AIM: Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children. METHODS...

  8. Myocarditis in auto-immune or auto-inflammatory diseases. (United States)

    Comarmond, Cloé; Cacoub, Patrice


    Myocarditis is a major cause of heart disease in young patients and a common precursor of heart failure due to dilated cardiomyopathy. Some auto-immune and/or auto-inflammatory diseases may be accompanied by myocarditis, such as sarcoidosis, Behçet's disease, eosinophilic granulomatosis with polyangiitis, myositis, and systemic lupus erythematosus. However, data concerning myocarditis in such auto-immune and/or auto-inflammatory diseases are sparse. New therapeutic strategies should better target the modulation of the immune system, depending on the phase of the disease and the type of underlying auto-immune and/or auto-inflammatory disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A rare case of autoimmune limbic encephalitis: an uncharted territory! (United States)

    Ibrahim, Hatim; Al Jasser, Abdulelah N; Khan, Sonia A; Tlili, Kalthoum G


    Autoimmune encephalitis is rare. Several auto- antibodies are described in autoimmune encephalitis. We describe a case of autoimmune limbic encephalitis associated with positive voltage gated potassium channel (VGKC) antibodies and positive leucine-rich glioma inactivated protein 1 antibodies (LGI1). A 33-year-old Saudi housewife, she presented with 2 months history of cognitive deterioration and recurrent left facio-brachial dystonic seizures followed by generalized tonic clonic seizures. At times the seizures are preceded by rising epigastric aura and shortness of breath. The neurological examination was normal apart from upgoing left plantar reflex. She had borderline IQ of 76 with impaired verbal fluency and impaired visual and verbal memory. Magnetic resonance imaging of the brain showed right mesial temporal non-enhancing lesion. Cerebrospinal fluid examination was positive for LGI1 and VGKC. Optimal seizure control was achieved with immunotherapy.

  10. Cancer and autoimmunity: Harnessing longitudinal cohorts to probe the link. (United States)

    Egiziano, Giordano; Bernatsky, Sasha; Shah, Ami A


    In many autoimmune rheumatic diseases, there is an increased risk of cancer compared to the general population. While reasons for this increased risk have not been elucidated, it has been hypothesized that the link between cancer and autoimmunity may be bidirectional. For instance, chronic inflammation and damage from the rheumatic disease or its therapies may trigger malignant transformation; conversely, antitumor immune responses targeting cancers may become cross-reactive resulting in autoimmunity. In rare rheumatic diseases, longitudinal observational studies can play a critical role in studying these complex relationships, thereby enabling investigators to quantify the extent of cancer risk, identify unique clinical phenotypes associated with cancer, investigate the biological link between these conditions, and define optimal strategies for screening and treatment of the underlying cancer. In this review, we discuss recent data on cancer in the rheumatic diseases and suggest a research agenda to address several gaps in our current knowledge base. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Biomimetic Nanosponges for Treating Antibody-Mediated Autoimmune Diseases. (United States)

    Jiang, Yao; Fang, Ronnie H; Zhang, Liangfang


    Autoimmune diseases are characterized by overactive immunity, where the body's defense system launches an attack against itself. If left unchecked, this can result in the destruction of healthy tissue and significantly affect patient well-being. In the case of type II autoimmune hypersensitivities, autoreactive antibodies attack the host's own cells or extracellular matrix. Current clinical treatment modalities for managing this class of disease are generally nonspecific and face considerable limitations. In this Topical Review, we cover emerging therapeutic strategies, with an emphasis on novel nanomedicine platforms. Specifically, the use of biomimetic cell membrane-coated nanosponges that are capable of specifically binding and neutralizing pathological antibodies will be explored. There is significant untapped potential in the application of nanotechnology for the treatment of autoimmune diseases, and continued development along this line may help to eventually change the clinical landscape.

  12. Environmental chemicals and autoimmune disease: cause and effect

    International Nuclear Information System (INIS)

    Hess, Evelyn V.


    Many important clues have been provided by the relationship of certain medications to lupus and other autoimmune syndromes. These are temporary conditions that resolve when the medication is removed. There are now over 70 such medications which have been reported related to these autoimmune conditions. Interest continues to grow in the potential for environmental substances to cause these syndromes. Among those under suspicion are hydrazines, tartrazines, hair dyes, trichloroethylene, industrial emissions and hazardous wastes. Other possible associations include silica, mercury, cadmium, gold and L canavanine. Two recognised outbreaks include 'toxic oil syndrome' related to contaminated rape seed oil in Spain in 1981 and exposure to a contaminated environmental substance associated with an autoimmune attack on muscle tissue in 1989. Recently, there have been proposals made for the definition and identification of environmentally associated immune disorders. The World Health Organisation (WHO) has also provided recent publications for other environmentally related problems. All these aspects will be presented and reviewed in detail

  13. Drug targets in the cytokine universe for autoimmune disease. (United States)

    Liu, Xuebin; Fang, Lei; Guo, Taylor B; Mei, Hongkang; Zhang, Jingwu Z


    In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the 'cytokine milieu' that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. PHM Enabled Autonomous Propellant Loading Operations (United States)

    Walker, Mark; Figueroa, Fernando


    The utility of Prognostics and Health Management (PHM) software capability applied to Autonomous Operations (AO) remains an active research area within aerospace applications. The ability to gain insight into which assets and subsystems are functioning properly, along with the derivation of confident predictions concerning future ability, reliability, and availability, are important enablers for making sound mission planning decisions. When coupled with software that fully supports mission planning and execution, an integrated solution can be developed that leverages state assessment and estimation for the purposes of delivering autonomous operations. The authors have been applying this integrated, model-based approach to the autonomous loading of cryogenic spacecraft propellants at Kennedy Space Center.

  15. Autonomic symptoms in idiopathic REM behavior disorder

    DEFF Research Database (Denmark)

    Ferini-Strambi, Luigi; Oertel, Wolfgang; Dauvilliers, Yves


    Patients with idiopathic REM sleep behavior disorder (iRBD) are at very high risk of developing neurodegenerative synucleinopathies, which are disorders with prominent autonomic dysfunction. Several studies have documented autonomic dysfunction in iRBD, but large-scale assessment of autonomic...... symptoms has never been systematically performed. Patients with polysomnography-confirmed iRBD (318 cases) and controls (137 healthy volunteers and 181 sleep center controls with sleep diagnoses other than RBD) were recruited from 13 neurological centers in 10 countries from 2008 to 2011. A validated scale...

  16. Cumulative childhood stress and autoimmune diseases in adults. (United States)

    Dube, Shanta R; Fairweather, DeLisa; Pearson, William S; Felitti, Vincent J; Anda, Robert F; Croft, Janet B


    To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0-8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p or=2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses.

  17. [Maternal autoimmune thyroid disease: relevance for the newborn]. (United States)

    Temboury Molina, M Carmen; Rivero Martín, M José; de Juan Ruiz, Jesús; Ares Segura, Susana


    Autoimmune thyroid disease is amongst the most frequent endocrine disorders during pregnancy. It is associated with an increase in perinatal morbidity, congenital defects, neurological damage, fetal and neonatal thyroid dysfunction. Maternal thyroid hormones play a key role in child neurodevelopment. We aimed to evaluate the thyroid function and the clinical course of neonates born from mothers with autoimmune thyroid disease during the first months of life in order to define the follow-up. We monitored thyroid function and clinical status during the first months in 81 newborns of mothers with autoimmune thyroid disease; 16 had Graves disease and 65 autoimmune thyroiditis. A percentage of 4.93 newborns had congenital defects, and 8.64% neonates showed an increase in thyrotropin (TSH) (>9.5 μUI/mL 2 times) and required thyroxin within the first month of life. A 85.7% of these showed a negative newborn screening (due to a later increase of TSH). A higher TSH value in the newborn was related to an older age of the mother, higher levels of thyroid peroxidase (TPO) antibody during pregnancy and lower birth weight. A higher free thyroxine (FT4) value in the newborn was related to fewer days of life and mothers with Graves disease. We recommend the evaluation of TSH, T4 and TPO antibodies before 10 weeks in all pregnant women with follow-up if maternal thyroid autoimmunity or disorders is detected. It is also recommended to test children's serum TSH and FT4 at 48 h of life in newborns of mothers with autoimmune thyroid disease and repeat them between the 2nd and 4th week in children with TSH>6 μUI/mL. Careful endocrine follow-up is advised in pregnant women and children if hyperthyroidism is detected. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  18. Regulatory dendritic cells in autoimmunity: A comprehensive review. (United States)

    Liu, Juan; Cao, Xuetao


    Dendritic cells (DCs) are professional antigen-presenting cells (APC) with significant phenotypic heterogeneity and functional plasticity. DCs play crucial roles in initiating effective adaptive immune responses for elimination of invading pathogens and also in inducing immune tolerance toward harmless components to maintain immune homeostasis. The regulatory capacity of DCs depends on their immature state and distinct subsets, yet not restricted to the immature state and one specialized subset. The tolerogenicity of DC is controlled by a complex network of environmental signals and cellular intrinsic mechanisms. Regulatory DCs play an important role in the maintenance of immunological tolerance via the induction of T cell unresponsiveness or apoptosis, and generation of regulatory T cells. DCs play essential roles in driving autoimmunity via promoting the activation of effector T cells such as T helper 1 and T helper 17 cells, and/or suppressing the generation of regulatory T cells. Besides, a breakdown of DCs-mediated tolerance due to abnormal environmental signals or breakdown of intrinsic regulatory mechanisms is closely linked with the pathogenesis of autoimmune diseases. Novel immunotherapy taking advantage of the tolerogenic potential of regulatory DCs is being developed for treatment of autoimmune diseases. In this review, we will describe the current understanding on the generation of regulatory DC and the role of regulatory DCs in promoting tolerogenic immune responses and suppressing autoimmune responses. The emerging roles of DCs dysfunction in the pathogenesis of autoimmune diseases and the potential application of regulatory DCs in the treatment of autoimmune diseases will also be discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Mercury and autoimmunity: implications for occupational and environmental health

    International Nuclear Information System (INIS)

    Silbergeld, Ellen K.; Silva, Ines A.; Nyland, Jennifer F.


    Mercury (Hg) has long been recognized as a neurotoxicant; however, recent work in animal models has implicated Hg as an immunotoxicant. In particular, Hg has been shown to induce autoimmune disease in susceptible animals with effects including overproduction of specific autoantibodies and pathophysiologic signs of lupus-like disease. However, these effects are only observed at high doses of Hg that are above the levels to which humans would be exposed through contaminated fish consumption. While there is presently no evidence to suggest that Hg induces frank autoimmune disease in humans, a recent epidemiological study has demonstrated a link between occupational Hg exposure and lupus. In our studies, we have tested the hypothesis that Hg does not cause autoimmune disease directly, but rather that it may interact with triggering events, such as genetic predisposition, exposure to antigens, or infection, to exacerbate disease. Treatment of mice that are not susceptible to Hg-induced autoimmune disease with very low doses and short term exposures of inorganic Hg (20-200 μg/kg) exacerbates disease and accelerates mortality in the graft versus host disease model of chronic lupus in C57Bl/6 x DBA/2 mice. Furthermore, low dose Hg exposure increases the severity and prevalence of experimental autoimmune myocarditis (induced by immunization with cardiac myosin peptide in adjuvant) in A/J mice. To test our hypothesis further, we examined sera from Amazonian populations exposed to Hg through small-scale gold mining, with and without current or past malaria infection. We found significantly increased prevalence of antinuclear and antinucleolar antibodies and a positive interaction between Hg and malaria. These results suggest a new model for Hg immunotoxicity, as a co-factor in autoimmune disease, increasing the risks and severity of clinical disease in the presence of other triggering events, either genetic or acquired

  20. MRI findings in glutamic acid decarboxylase associated autoimmune epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Fredriksen, Jason R.; Carr, Carrie M.; Koeller, Kelly K.; Verdoorn, Jared T.; Kotsenas, Amy L. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Gadoth, Avi; Pittock, Sean J. [Mayo Clinic, Department of Neurology, Rochester, MN (United States)


    Glutamic acid decarboxylase (GAD65) has been implicated in a number of autoimmune-associated neurologic syndromes, including autoimmune epilepsy. This study categorizes the spectrum of MRI findings in patients with a clinical diagnosis of autoimmune epilepsy and elevated serum GAD65 autoantibodies. An institutional database search identified patients with elevated serum GAD65 antibodies and a clinical diagnosis of autoimmune epilepsy who had undergone brain MRI. Imaging studies were reviewed by three board-certified neuroradiologists and one neuroradiology fellow. Studies were evaluated for cortical/subcortical and hippocampal signal abnormality, cerebellar and cerebral volume loss, mesial temporal sclerosis, and parenchymal/leptomeningeal enhancement. The electronic medical record was reviewed for relevant clinical information and laboratory markers. A study cohort of 19 patients was identified. The majority of patients were female (84%), with a mean age of onset of 27 years. Serum GAD65 titers ranged from 33 to 4415 nmol/L (normal < 0.02 nmol/L). The most common presentation was medically intractable, complex partial seizures with temporal lobe onset. Parenchymal atrophy was the most common imaging finding (47%), with a subset of patients demonstrating cortical/subcortical parenchymal T2 hyperintensity (37%) or abnormal hippocampal signal (26%). No patients demonstrated abnormal parenchymal/leptomeningeal enhancement. The most common MRI finding in GAD65-associated autoimmune epilepsy is disproportionate parenchymal atrophy for age, often associated with abnormal cortical/subcortical T2 hyperintensities. Hippocampal abnormalities are seen in a minority of patients. This constellation of findings in a patient with medically intractable epilepsy should raise the possibility of GAD65 autoimmunity. (orig.)