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Sample records for autoimmune type atrophic

  1. Association of autoimmune type atrophic corpus gastritis with Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Lea; Irene; Veijola; Aino; Mirjam; Oksanen; Pentti; Ilmari; Sipponen; Hilpi; Iris; Kaarina; Rautelin

    2010-01-01

    AIM:To study the association between Helicobacter pylori(H.pylori)infection and autoimmune type atrophic gastritis. METHODS:Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology,immunoblot-based serology,and histology to reveal a past or a present H.pylori infection.In addition,serum markers for gastric atrophy(pepsinogenⅠ,pepsinogenⅠ/Ⅱand gastrin)and autoimmunity[parietal cell antibodies(PCA), and intrinsic factor(IF),antibodies]were determi...

  2. Autoimmune atrophic gastritis: current perspectives

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    Minalyan, Artem; Benhammou, Jihane N; Artashesyan, Aida; Lewis, Michael S; Pisegna, Joseph R

    2017-01-01

    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. PMID:28223833

  3. Upregulation of cathepsin W-expressing T cells is specific for autoimmune atrophic gastritis compared to other types of chronic gastritis

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    Doerthe Kuester; Michael Vieth; Ulrich Peitz; Stefan Kahl; Manfred Stolte; Albert Roessner; Ekkehard Weber; Peter Malfertheiner; Thomas Wex

    2005-01-01

    AIM: To investigate a pathophysiological role of cathepsin W (CatW), a putative thiol-dependent cysteine protease,which is specifically expressed in cytotoxic lymphocytes,in different types of chronic inflammation of the gastric mucosa.METHODS: Gastric and duodenal biopsies of patients with Helicobacter pylori ( H pylori)-associated active gastritis ( Hp,n = 19), chemically induced reactive gastritis (CG, n = 17),autoimmune atrophic gastritis (AIG, n = 20), lymphocytic corpus gastritis (LG, n = 29), celiac disease (CD, n = 10),and corresponding controls (n = 24) were analyzed by immunohistochemistry for the expression of CatW and CD45. Furthermore, immunohistochemical double staining with anti-CD3 and anti-cathepsin was performed for the samples of AIG.RESULTS: Median values of CatW-expressing cells among CD45-positive immune cells were between 2% and 6% for normal gastric mucosa, CG, and LG, whereas the corresponding value was significantly increased for AIG (24.7%, P<0.001) and significantly decreased for HP (0.7%, P<0.05). Double staining with anti-CD3 and antiCatW antibodies revealed that >90% of CatW-expressing cells in gastric mucosa of AIG were T cells. Duodenal mucosa had significantly more CatW/CD45-positive cells than normal gastric mucosa (median: 17.8% vs 2%, P<0.01).The corresponding proportion of CatW/CD45-positive cells was decreased in CD compared to duodenal mucosa (median: 2.1% vs 17.8%, P<0.05).CONCLUSION: The opposite findings regarding the presence of CatW-positive cells in AIG (increase) and CD (decrease) reflects the different cellular composition of immune cells involved in the pathogenesis of these diseases.

  4. Differential proteomics of Helicobacter pylori associated with autoimmune atrophic gastritis.

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    Repetto, Ombretta; Zanussi, Stefania; Casarotto, Mariateresa; Canzonieri, Vincenzo; De Paoli, Paolo; Cannizzaro, Renato; De Re, Valli

    2014-02-28

    Atrophic autoimmune gastritis (AAG) is a condition of chronic inflammation and atrophy of stomach mucosa, for which development can be partially triggered by the bacterial pathogen Helicobacter pylori (HP). HP can cause a variety of gastric diseases, such as duodenal ulcer (DU) or gastric cancer (GC). In this study, a comparative proteomic approach was used by two-dimensional fluorescence difference gel electrophoresis (DIGE) to identify differentially expressed proteins of HP strains isolated from patients with AAG, to identify markers of HP strain associated with AAG. Proteome profiles of HP isolated from GC or DU were used as a reference to compare proteomic levels. Proteomics analyses revealed 27 differentially expressed spots in AAG-associated HP in comparison with GC, whereas only 9 differential spots were found in AAG-associated HP profiles compared with DU. Proteins were identified after matrix-assisted laser desorption ionization (MALDI)-TOF and peptide mass fingerprinting. Some AAG-HP differential proteins were common between DU- and GC-HP (peroxiredoxin, heat shock protein 70 [HSP70], adenosine 5'-triphosphate [ATP] synthase subunit α, flagellin A). Our results presented here may suggest that comparative proteomes of HP isolated from AAG and DU share more common protein expression than GC and provide subsets of putative AAG-specific upregulated or downregulated proteins that could be proposed as putative markers of AAG-associated HP. Other comparative studies by two-dimensional maps integrated with functional genomics of candidate proteins will undoubtedly contribute to better decipher the biology of AAG-associated HP strains.

  5. Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis

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    Bruno Annibale; Edith Lahner; Riccardo Negrini; Flavia Baccini; Cesare Bordi; Bruno Monarca; Gianfranco Delle Fave

    2005-01-01

    AIM: To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients.METHODS: A total of 140 atrophic body gastritis patients,diagnosed as consecutive outpatients presenting with macrocytic or iron deficiency anemia, or longstanding dyspepsia underwent gastroscopy with antral and body biopsies, assay of intrinsic factor, parietal cells and Helicobacter pylori(H pylori) antibodies. Gastritis was assessed according to Sydney System.RESULTS: Parietal cell antibodies were equally distributed in all clinical presentations, whereas the positivity of intrinsic factor antibodies (49/140, 35%) was significantly higher in pernicious anemia patients (49.2%) than in iron deficiency (21.1%) and dyspeptic patients (27.8%). No specific pattern of autoantibodies was related to the clinical presentations of atrophic body gastritis. A positive correlation was obtained between the body atrophy score and the intrinsic factor antibody levels (r = 0.2216,P = 0.0085). Associated autoimmune diseases were present in 25/140 (17.9%) patients, but the prevalence of autoimmune diseases was comparable, irrespective of the clinical presentations.CONCLUSION: The so-called hallmarks of gastric autoimmunity, particularly in intrinsic factor antibody cannot be usefully employed in defining an autoimmune pattern in the clinical presentations of ABG.

  6. Study on histogenesis of enterochromaffin-like carcinoid in autoimmune atrophic gastritis associated with pernicious anemia

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    Mačukanović-Golubović Lana

    2007-01-01

    Full Text Available Background/Aim. Autoimmune atrophic fundic gastritis induces the pernicious anemia (PA, as well as the changes in both epithelium and endocrine cells of gastric mucosa. The most important complications are: achlorhydria, hypergastrinemia, gastric cancer and enterochromaffin-like ( ECL carcinoid. The aim of this study was to examine ECL carcinoid histogenesis in A-gastritis associated with PA. Methods. During the period from 2000−2006, 65 patients with PA and 30 patients of the control group were examined. Histopathological examination was done in endoscopical biopsies of gastric mucosa fixed in 10% formaldehyde. Paraffin sections were stained with classic hematoxylin-eosin (HE; histochemical AB-PAS (pH 2.5, cytochemical argyrophilic Servier-Munger′s and immunocytochemical PAP methods for G cell identification and chromogranin A antibodies - specific marker for neuroendocrine ECL cells. Both G and ECL cells were counted per 20 fields, of surface 0.0245312 mm2 by a field. Basal gastrin serum levels were also examined by using radioimmunoassay (RIA method. The obtained results were statisticaly calculated by using Student΄s t test. Results. Marked antral G cell hyperplasia associated with corporal ECL hyperplasia was found. ECL cell hyperplasia was of simplex, linear, adenomatoid type to the pattern of intramucous ECL cell carcinoid. An average number of G cells was statistically significant in the patients with PA as compared to the control group (p < 0.05 as well as an average number of ECL cells. Conclusion. We concluded that antral G cell hyperplasia accompanied by gastrinemia induces ECL hyperplasia and ECL corporal carcinoid in A-gastritis and that their histogenesis develops trough simple, linear and adenomatoide hyperplasia. .

  7. Micronutrient deficiencies in patients with chronic atrophic autoimmune gastritis: A review

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    Cavalcoli, Federica; Zilli, Alessandra; Conte, Dario; Massironi, Sara

    2017-01-01

    Chronic atrophic autoimmune gastritis (CAAG) is an organ-specific autoimmune disease characterized by an immune response, which is directed towards the parietal cells and intrinsic factor of the gastric body and fundus and leads to hypochlorhydria, hypergastrinemia and inadequate production of the intrinsic factor. As a result, the stomach’s secretion of essential substances, such as hydrochloric acid and intrinsic factor, is reduced, leading to digestive impairments. The most common is vitamin B12 deficiency, which results in a megaloblastic anemia and iron malabsorption, leading to iron deficiency anemia. However, in the last years the deficiency of several other vitamins and micronutrients, such as vitamin C, vitamin D, folic acid and calcium, has been increasingly described in patients with CAAG. In addition the occurrence of multiple vitamin deficiencies may lead to severe hematological, neurological and skeletal manifestations in CAAG patients and highlights the importance of an integrated evaluation of these patients. Nevertheless, the nutritional deficiencies in CAAG are largely understudied. We have investigated the frequency and associated features of nutritional deficiencies in CAAG in order to focus on any deficit that may be clinically significant, but relatively easy to correct. This descriptive review updates and summarizes the literature on different nutrient deficiencies in CAAG in order to optimize the treatment and the follow-up of patients affected with CAAG. PMID:28216963

  8. Type 1 autoimmune pancreatitis

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    Zen Yoh

    2011-12-01

    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

  9. Type 1 diabetes associated autoimmunity.

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    Kahaly, George J; Hansen, Martin P

    2016-07-01

    Diabetes mellitus is increasing in prevalence worldwide. The economic costs are considerable given the cardiovascular complications and co-morbidities that it may entail. Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the loss of insulin-producing pancreatic β-cells. The pathogenesis of T1D is complex and multifactorial and involves a genetic susceptibility that predisposes to abnormal immune responses in the presence of ill-defined environmental insults to the pancreatic islets. Genetic background may affect the risk for autoimmune disease and patients with T1D exhibit an increased risk of other autoimmune disorders such as autoimmune thyroid disease, Addison's disease, autoimmune gastritis, coeliac disease and vitiligo. Approximately 20%-25% of patients with T1D have thyroid antibodies, and up to 50% of such patients progress to clinical autoimmune thyroid disease. Approximately 0.5% of diabetic patients have concomitant Addison's disease and 4% have coeliac disease. The prevalence of autoimmune gastritis and pernicious anemia is 5% to 10% and 2.6% to 4%, respectively. Early detection of antibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown disease. Patients and family members should be educated to be able to recognize signs and symptoms of underlying disease.

  10. Autoimmune Polyglandular Syndrome Type 1

    OpenAIRE

    Ponranjini, Vedeswari C.; Jayachandran, S; L Kayal; K Bakyalakshmi

    2012-01-01

    Autoimmune Polyglandular Syndrome (APS) Type 1 is a rare hereditary disorder that damages organs in the body. This disease entity is the result of a mutation in the AIRE gene. It is characterized by three classic clinical features - hypoparathyroidism, Addison′s disease, and chronic mucocutaneous candidiasis. For a patient to be diagnosed as having APS Type 1 syndrome at least two of these features needs to be present. The third entity may develop as the disease progresses. We report a case o...

  11. Autoimmune diseases associated with neurofibromatosis type 1.

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    Nanda, Arti

    2008-01-01

    Associations of autoimmune diseases with neurofibromatosis type 1 have been rarely described. In the present report, we describe two patients of neurofibromatosis type 1 having an association with vitiligo in one, and alopecia areata and autoimmune thyroiditis in another. The associations of neurofibromatosis type 1 with vitiligo, alopecia areata, and autoimmune thyroiditis have not been reported earlier. Whether these associations reflect a causal relationship with neurofibromatosis type 1 or are coincidental needs to be settled.

  12. Autoimmune Polyglandular Syndrome Type 1

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    Vedeswari C Ponranjini

    2012-01-01

    Full Text Available Autoimmune Polyglandular Syndrome (APS Type 1 is a rare hereditary disorder that damages organs in the body. This disease entity is the result of a mutation in the AIRE gene. It is characterized by three classic clinical features - hypoparathyroidism, Addison′s disease, and chronic mucocutaneous candidiasis. For a patient to be diagnosed as having APS Type 1 syndrome at least two of these features needs to be present. The third entity may develop as the disease progresses. We report a case of a 35-year-old female patient with a history of seizure from the age of 11 years, who was managed with anticonvulsant drugs. With worsening of the seizure episodes, patient was diagnosed to have hypoparathyroidism together with the manifestations of oral candidiasis, nails dystrophy, enamel hypoplasia, and hypogonadism. A diagnosis of APS-1 was considered. The facility for genetic analysis of the AIRE gene mutation was not accessible, as the test costs were prohibitive and not affordable for the patient. Patient management was directed to treating individual disease components. However, cerebral and dental changes were irreversible.

  13. Autoimmunity and type I diabetes.

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    Bach, J F

    1997-03-01

    Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease. The effector mechanisms essentially involve cytokine-mediated inflammation ultimately leading to beta-cell destruction. Several candidate autoantigens have been delineated for both the pathogenic T-cell response and the nonpathogenic antibody response used for disease prediction. Because of antigen spreading, it is not yet clear which of these antigens are involved in the triggering of the autoimmune response. In any case, this TH1 autoimmune response is amplified and perpetuated by an immune dysregulation involving TH2 cells. Both effector and regulatory mechanisms are placed under the tight control of major histocompatibility complex (MHC) and non-MHC genes. (Trends Endocrinol Metab 1997; 8:71-74). (c) 1997, Elsevier Science Inc.

  14. An autosomal locus causing autoimmune disease: Autoimmune polyglandular disease type I assigned to chromosome 21

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    J. Aaltonen (Johanna); P. Björses (Petra); L.A. Sandkuijl (Lodewijk); J. Perheentupa (Jaakko); L. Peltonen (Leena Johanna)

    1994-01-01

    textabstractAutoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease characterized by a variable combination of the failure of the endocrine glands. The pathogenesis of this unique autoimmune disease is unknown; unlike many other autoimmune diseases, APECED does

  15. Rehabilitation of atrophic maxilla using the combination of autogenous and allogeneic bone grafts followed by protocol-type prosthesis.

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    Margonar, Rogério; dos Santos, Pâmela Letícia; Queiroz, Thallita Pereira; Marcantonio, Elcio

    2010-11-01

    Currently, there are several techniques for the rehabilitation of atrophic maxillary ridges in literature. The grafting procedure using autogenous bone is considered ideal by many researchers, as it shows osteogenic capability and causes no antigenic reaction. However, this type of bone graft has some shortcomings, mainly the restricted availability of donor sites. In recent years, several alternatives have been investigated to supply the disadvantages of autogenous bone grafts. In such studies, allogeneic bone grafts, which are obtained from individuals with different genetic load, but from the same species, have been extensively used. They can be indicated in cases of arthroplasty, surgical knee reconstruction, large bone defects, and in oral and maxillofacial reconstruction. Besides showing great applicability and biocompatibility, this type of bone is available in unlimited quantities. On the other hand, allogeneic bone may have the disadvantage of transmitting infectious diseases. Atrophic maxillae can be treated with bone grafts followed by osseointegrated implants to obtain aesthetic and functional oral rehabilitation. This study aimed to show the viability of allogeneic bone grafting in an atrophic maxilla, followed by oral rehabilitation with dental implant and protocol-type prosthesis within a 3-year follow-up period by means of a clinical case report.

  16. Stomach microbiota composition varies between patients with non-atrophic gastritis and patients with intestinal type of gastric cancer.

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    Aviles-Jimenez, Francisco; Vazquez-Jimenez, Flor; Medrano-Guzman, Rafael; Mantilla, Alejandra; Torres, Javier

    2014-02-26

    We aimed to characterize microbiota of the gastric mucosa as it progress to intestinal type of cancer. Study included five patients each of non-atrophic gastritis (NAG), intestinal metaplasia (IM) and intestinal-type gastric cancer (GC). Gastric tissue was obtained and DNA extracted for microbiota analyses using the microarray G3 PhyloChip. Bacterial diversity ranged from 8 to 57, and steadily decreased from NAG to IM to GC (p = 0.004). A significant microbiota difference was observed between NAG and GC based on Unifrac-presence/absence and weighted-Unifrac-abundance metrics of 283 taxa (p gastric microbiota profile from NAG to IM to GC.

  17. [Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus].

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    Krysiak, Robert; Okopień, Bogusław

    2015-01-01

    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

  18. Fulminant hepatic failure in autoimmune polyendocrine syndrome type-1.

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    Sinha, R; Chapman, A R; Reid, G T; Hayes, P C

    2015-01-01

    Fulminant hepatic failure is liver disease that causes encephalopathy within 8 weeks of onset of symptoms or within 2 weeks of onset of jaundice in a patient without prior evidence of liver disease. Autoimmune polyendocrine syndrome type-1 is an autoimmune autosomal-recessive condition causing parathyroid and adrenal insufficiency, alopecia, chronic mucocutaneous candidiasis, ectodermal dystrophy and, rarely, hepatitis. Although the liver can be affected as a consequence of the autoimmune process, the spectrum of disease activity is varied. Autoimmune hepatitis develops in 10-20% of patients and successful liver transplantation has been reported in pediatric patients who failed immunosuppressive treatment. We report fulminant hepatic failure in an adult patient with autoimmune polyendocrine syndrome type-1 who responded to medical treatment and did not require liver transplantation. We highlight the diagnostic scoring system for autoimmune hepatitis and the referral criteria for liver transplantation in fulminant hepatic failure.

  19. Autoimmune Polyglandular Syndrome Type 3 with Anorexia

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    Toshio Kahara

    2012-01-01

    Full Text Available A 71-year-old man with diabetes mellitus visited our hospital with complaints of anorexia and weight loss (12 kg/3 months. He had megaloblastic anemia, cobalamin level was low, and autoantibody to intrinsic factor was positive. He was treated with intramuscular cyanocobalamin, and he was able to consume meals. GAD autoantibody and ICA were positive, and he was diagnosed with slowly progressive type 1 diabetes mellitus (SPIDDM. Thyroid autoantibodies were positive. According to these findings, he was diagnosed with autoimmune polyglandular syndrome type 3 with SPIDDM, pernicious anemia, and Hashimoto's thyroiditis. Extended periods of cobalamin deficiency can cause serious complications such as ataxia and dementia, and these complications may not be reversible if replacement therapy with cobalamin is delayed. Although type 1 diabetes mellitus with coexisting pernicious anemia is very rare in Japan, physicians should consider the possibility of pernicious anemia when patients with diabetes mellitus have cryptogenic anorexia with the finding of significant macrocytosis (MCV > 100 fL.

  20. Netazepide, a gastrin receptor antagonist, normalises tumour biomarkers and causes regression of type 1 gastric neuroendocrine tumours in a nonrandomised trial of patients with chronic atrophic gastritis.

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    Andrew R Moore

    Full Text Available INTRODUCTION: Autoimmune chronic atrophic gastritis (CAG causes hypochlorhydria and hypergastrinaemia, which can lead to enterochromaffin-like (ECL cell hyperplasia and gastric neuroendocrine tumours (type 1 gastric NETs. Most behave indolently, but some larger tumours metastasise. Antrectomy, which removes the source of the hypergastrinaemia, usually causes tumour regression. Non-clinical and healthy-subject studies have shown that netazepide (YF476 is a potent, highly selective and orally-active gastrin/CCK-2 receptor antagonist. Also, it is effective in animal models of ECL-cell tumours induced by hypergastrinaemia. AIM: To assess the effect of netazepide on tumour biomarkers, number and size in patients with type I gastric NETs. METHODS: We studied 8 patients with multiple tumours and raised circulating gastrin and chromogranin A (CgA concentrations in an open trial of oral netazepide for 12 weeks, with follow-up 12 weeks later. At 0, 6, 12 and 24 weeks, we carried out gastroscopy, counted and measured tumours, and took biopsies to assess abundances of several ECL-cell constituents. At 0, 3, 6, 9, 12 and 24 weeks, we measured circulating gastrin and CgA and assessed safety and tolerability. RESULTS: Netazepide was safe and well tolerated. Abundances of CgA (p<0.05, histidine decarboxylase (p<0.05 and matrix metalloproteinase-7(p<0.10 were reduced at 6 and 12 weeks, but were raised again at follow-up. Likewise, plasma CgA was reduced at 3 weeks (p<0.01, remained so until 12 weeks, but was raised again at follow-up. Tumours were fewer and the size of the largest one was smaller (p<0.05 at 12 weeks, and remained so at follow-up. Serum gastrin was unaffected. CONCLUSION: The reduction in abundances, plasma CgA, and tumour number and size by netazepide show that type 1 NETs are gastrin-dependent tumours. Failure of netazepide to increase serum gastrin further is consistent with achlorhydria. Netazepide is a potential new treatment for type 1 NETs

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

    OpenAIRE

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

    2014-01-01

    Context 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. Case presentation 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 reveale...

  2. Autoimmune Polyglandular Syndrome Type 2: An Unusual Presentation

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    Hamdollah Karamifar

    2010-05-01

    Full Text Available "nAutoimmune polyglandular syndrome (APS type 2 is characterized by the presence of Addison's disease, in association with autoimmune thyroid disease and/or type 1 diabetes mellitus. APS type 2 occurs most often in middle aged females and is rare in children. Here an 11 year old boy is reported with Addison's disease who developed symptom's of diabetes mellitus, goiter, malabsorption, macrocytic anemia and keratitis. APS type 2 occurs most often in middle aged females and is quite rare in children but one should think to autoimmune poly glandular syndrome type II in patient at any age especially in patients with Addison's disease.

  3. Recent advances in autoimmune pancreatitis: type 1 and type 2.

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    Kamisawa, Terumi; Chari, Suresh T; Lerch, Markus M; Kim, Myung-Hwan; Gress, Thomas M; Shimosegawa, Tooru

    2013-09-01

    Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis characterised clinically by frequent presentation with obstructive jaundice, histologically by a lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response to steroids. When so defined, AIP can be sub-classified into two subtypes, 1 and 2. Recent international consensus diagnostic criteria for AIP have been developed for diagnosis of both forms of AIP. Type 1 AIP is the pancreatic manifestation of a multiorgan disease, recently named IgG4-related disease. Little is known about the pathogenesis of either form of AIP. Despite frequent association of type 1 AIP with elevated serum IgG4 levels and infiltration with IgG4-positive plasma cells, it is unlikely that IgG4 plays a pathogenic role in AIP. Type 1 AIP responds to steroids, but there needs to be consensus on treatment regimens for induction and therapeutic end points. Relapses are common, but can be reduced by long-term use of low-dose steroids. Recent reports suggest that immunomodulators (azathioprine, 6-mercaptopurine and mycophenolate mofetil), as well biological agents (the antibody to CD20, rituximab) may have a role in maintaining remission in relapsing type 1 AIP. Future studies should clarify the best management options for treatment of relapses and maintenance of remission. Type 2 AIP is a pancreas-specific disorder not associated with IgG4. It presents in younger individuals equally with obstructive jaundice and pancreatitis. The inflammatory process responds to steroid therapy; relapses are uncommon. The clinical spectrum and long-term outcomes of medically treated type 2 AIP are still being evaluated.

  4. Interferon Type I Driven Immune Activation in Generalized Autoimmune Diseases

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    Z. Brkić (Zana)

    2013-01-01

    textabstractThis thesis describes research performed on several generalized autoimmune diseases with the main focus on primary Sjögren’s syndrome. Interferon type I has been implicated in the pathogenesis of these diseases and will be introduced in this chapter together with other important immune f

  5. [Autoimmune diseases in type 1A diabetes mellitus].

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    Ferreira-Hermosillo, Aldo; Molina-Ayala, Mario Antonio

    2015-08-01

    Type 1A diabetes (DM1A) is an autoimmune disease that comprises 10% of patients with diabetes mellitus. Its frequency is gradually increasing in countries like Mexico. Patients with DM1A commonly have hypothyroidism, Addison disease, celiac disease and less common diseases such as polyglandular syndrome. These diseases are related to susceptibility genes such as HLA, CTLA-4 and PTPN22, which induce central and peripheral immunologic tolerance. This review article emphasizes the importance of searching other autoimmune diseases in patients with DM1A, to improve their prognosis and quality of life.

  6. [Autoimmune mechanisms toward type I collagen during parodontitis].

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    2014-04-01

    The article presents original data about autoimmune mechanisms according to the severity of the process during the chronic generalized Parodontitis. The medical examination of 179 patients with different forms of Parodontitis demonstrated that during Parodontitis the synthesis and re-synthesis of type I Collagen is negatively affected and as a result, type I Collagen concentration in the blood serum raises. In addition, the selection of antigen reactive lymphocytes increases toward Type I Collagen, which in turn boosts their quantity in blood and also stimulates the creation of auto-antibodies toward Type I Collagen. This is reflected by the increased quantity of auto-antibodies in the blood serum. The intensity of these processes amplifies as the Parodontitis inflammation becomes more severe. These results demonstrate that the autoimmune process develops toward Type I Collagen during Parodontitis and its intensity reflects the severity of the pathological processes in Parodontitis.

  7. Type 1 diabetes and polyglandular autoimmune syndrome:A review

    Institute of Scientific and Technical Information of China (English)

    Martin P Hansen; Nina Matheis; George J Kahaly

    2015-01-01

    Type 1 diabetes (T1D) is an autoimmune disorder causedby inflammatory destruction of the pancreatic tissue. Theetiopathogenesis and characteristics of the pathologicprocess of pancreatic destruction are well described. Inaddition, the putative susceptibility genes for T1D as amonoglandular disease and the relation to polyglandularautoimmune syndrome (PAS) have also been wellexplored. The incidence of T1D has steadily increasedin most parts of the world, especially in industrializednations. T1D is frequently associated with autoimmuneendocrine and non-endocrine diseases and patients withT1D are at a higher risk for developing several glandularautoimmune diseases. Familial clustering is observed,which suggests that there is a genetic predisposition.Various hypotheses pertaining to viral- and bacterialinducedpancreatic autoimmunity have been proposed,however a definitive delineation of the autoimmunepathomechanism is still lacking. In patients with PAS,pancreatic and endocrine autoantigens either colocalizeon one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, whichfacilitates binding to and activation of T cells. The mostprevalent PAS phenotype is the adult type 3 variant orPAS type Ⅲ, which encompasses T1D and autoimmunethyroid disease. This review discusses the findings ofrecent studies showing noticeable differences in thegenetic background and clinical phenotype of T1D eitheras an isolated autoimmune endocrinopathy or within thescope of polyglandular autoimmune syndrome.

  8. Primary Biliary Cirrhosis and Type II Autoimmune Polyglandular Syndrome

    Directory of Open Access Journals (Sweden)

    Mark Ram Borgaonkar

    1999-01-01

    Full Text Available A 45-year-old female was diagnosed with Hashimoto’s thyroiditis in 1976 and Addison’s disease in 1979. At that time, her antimitochondrial antibody (AMA level was elevated at 1:32. She subsequently developed premature ovarian failure and type I diabetes mellitus. In 1996, she became jaundiced with a cholestatic enzyme pattern. AMA was positive at a titre of 1:256. A liver biopsy confirmed the diagnosis of primary biliary cirrhosis (PBC. She underwent a liver transplantation in January 1998. This is the first report of PBC in association with type II autoimmune polyglandular syndrome. The association of PBC with other organ-specific autoimmune diseases supports an immune-mediated pathogenesis and may have implications in further studies of PBC.

  9. Molecular mechanisms in autoimmune type 1 diabetes: a critical review.

    Science.gov (United States)

    Xie, Zhiguo; Chang, Christopher; Zhou, Zhiguang

    2014-10-01

    Autoimmune type 1 diabetes is characterized by selective destruction of insulin-secreting beta cells in the pancreas of genetically susceptible individuals. The mechanisms underlying the development of type 1 diabetes are not fully understood. However, a widely accepted point is that type 1 diabetes is caused by a combination of genetic and environmental factors. Although most type 1 diabetes patients do not have a family history, genetic susceptibility does play a vital role in beta cell autoimmunity and destruction. Human leukocyte antigen (HLA) regions are the strongest genetic determinants, which can contribute 40-50 % of the genetic risk to type 1 diabetes. Other genes, including INS also contribute to disease risk. The mechanisms of the susceptible genes in type 1 diabetes may relate to their respective roles in antigen presentation, beta cell autoimmunity, immune tolerance, and autoreactive T cell response. Environmental susceptibility factors also contribute to the risk of developing type 1 diabetes. From an epigenetic standpoint, the pathologic mechanisms involved in the development of type 1 diabetes may include DNA methylation, histone modification, microRNA, and molecular mimicry. These mechanisms may act through regulating of gene expression, thereby affecting the immune system response toward islet beta cells. One of the characteristics of type 1 diabetes is the recognition of islet autoantigens by autoreactive CD4(+) and CD8(+) T cells and autoantibodies. Autoantibodies against islet autoantigens are involved in autoantigen processing and presentation by HLA molecules. This review will mainly focus on the molecular mechanism by which genetic, epigenetic, and environmental factors contribute to the risk of type 1 diabetes.

  10. Detection of candidal antigens in autoimmune polyglandular syndrome type I.

    OpenAIRE

    Peterson, P; Perheentupa, J; Krohn, K J

    1996-01-01

    Autoimmune polyglandular syndrome type I (APS I) is associated with chronic mucocutaneous candidiasis. To characterize the antibody responses in this subgroup of Candida albicans infections, we screened a candidal cDNA expression library with patient sera and found four cDNA clones encoding the immunopositive proteins enolase, heat shock protein 90, pyruvate kinase, and alcohol dehydrogenase. The reactivity to these antigens was studied further by immunoprecipitation assays with in vitro-tran...

  11. Autoimmune gastritis: Pathologist's viewpoint.

    Science.gov (United States)

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

    2015-11-14

    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.

  12. Association of Helicobacter pylori infection with chronic atrophic gastritis: Meta-analyses according to type of disease definition.

    Science.gov (United States)

    Weck, Melanie N; Brenner, Hermann

    2008-08-15

    Helicobacter pylori is a major risk factor for chronic atrophic gastritis (CAG). A large variety of definitions of CAG have been used in epidemiologic studies in the past. The aim of this work was to systematically review and summarize estimates of the association between H. pylori infection and CAG according to the various definitions of CAG. Articles on the association between H. pylori infection and CAG published until July 2007 were identified. Separate meta-analyses were carried out for studies defining CAG based on gastroscopy with biopsy, serum pepsinogen I (PG I) only, the pepsinogen I/pepsinogen II ratio (PG I/PG II ratio) only, or a combination of PG I and the PG I/PG II ratio. Numbers of identified studies and summary odds ratios (OR) (95% confidence intervals) were as follows: gastroscopy with biopsy: n = 34, OR = 6.4 (4.0-10.1); PG I only: n = 13, OR = 0.9 (0.7-1.2); PG I/PG II ratio: n = 8, OR = 7.2 (3.1-16.8); combination of PG I and the PG I/PG II ratio: n = 20, OR = 5.7 (4.4-7.5). Studies with CAG definitions based on gastroscopy with biopsy or the PG I/PG II ratio (alone or in combination with PG I) yield similarly strong associations of H. pylori with CAG. The association is missed entirely in studies where CAG is defined by PG I only.

  13. Shock: A possible presenting manifestation of autoimmune polyendocrine syndrome type II

    Directory of Open Access Journals (Sweden)

    Subodh Banzal

    2014-01-01

    Full Text Available Autoimmune polyendocrine syndrome Type II (APS II, also known as polyglandular autoimmune syndrome Type II or Schmidt syndrome, is constellations of multiple endocrine gland insufficiencies. It is a rare, but most common of the immunoendocrinopathy syndrome. It is characterized by the obligatory occurrence of autoimmune Addison′s disease in combination with thyroid autoimmune diseases and/or Type I diabetes, hypogonadism, hypophysitis, myasthenia gravis, vitiligo, alopecia, pernicious anemia, and celiac disease. Here, we report a case of 38-year-old female patient presented with shock, further diagnosed to have APS II.

  14. Genetic homogeneity of autoimmune polyglandular disease type I

    Energy Technology Data Exchange (ETDEWEB)

    Bjoerses, P.; Aaltonen, J.; Vikman, A. [Univ. of Helsinki (Finland)] [and others

    1996-10-01

    Autoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease (MIM 240300) characterized by hypoparathyroidism, primary adrenocortical failure, and chronic mucocutaneous candidiasis. The disease is highly prevalent in two isolated populations, the Finnish population and the Iranian Jewish one. Sporadic cases have been identified in many other countries, including almost all European countries. The APECED locus has previously been assigned to chromosome 21q22.3 by linkage analyses in 14 Finnish families. Locus heterogeneity is a highly relevant question in this disease affecting multiple tissues and with great phenotypic diversity. To solve this matter, we performed linkage and haplotype analyses on APECED families rising from different populations. Six microsatellite markers on the critical chromosomal region of 2.6 cM on 21q22.3 were analyzed. Pair-wise linkage analyses revealed significant LOD scores for all these markers, maximum LOD score being 10.23. The obtained haplotype data and the geographic distribution of the great-grandparents of the Finnish APECED patients suggest the presence of one major, relatively old mutation responsible for {approximately}90% of the Finnish cases. Similar evidence for one founder mutation was also found in analyses of Iranian Jewish APECED haplotypes. These haplotypes, however, differed totally from the Finnish ones. The linkage analyses in 21 non-Finnish APECED families originating from several European countries provided independent evidence for linkage to the same chromosomal region on 21q22.3 and revealed no evidence for locus heterogeneity. The haplotype analyses of APECED chromosomes suggest that in different populations APECED is due to a spectrum of mutations in a still unknown gene on chromosome 21. 21 refs., 3 figs., 3 tabs.

  15. Bullous Skin Diseases: Classical Types of Autoimmune Diseases

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    Jan Damoiseaux

    2013-01-01

    Full Text Available The prototypic bullous skin diseases, pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid, are characterized by the blister formation in the skin and/or oral mucosa in combination with circulating and deposited autoantibodies reactive with (hemidesmosomes. Koch’s postulates, adapted for autoimmune diseases, were applied on these skin diseases. It appears that all adapted Koch’s postulates are fulfilled, and, therefore, these bullous skin diseases are to be considered classical autoimmune diseases within the wide and expanding spectrum of autoimmune diseases.

  16. Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa

    Energy Technology Data Exchange (ETDEWEB)

    Gatalica, B.; Pulkkinen, L.; Li, K. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1997-02-01

    Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal variant of junctional epidermolysis bullosa (JEB). Previous findings have suggested that type XVII collagen is the candidate gene for mutations in this disease. We now have cloned the entire human type XVII collagen gene (COL17A1) and have elucidated its intron-exon organization. The gene comprises 56 distinct exons, which span {approximately}52 kb of the genome, on the long arm of chromosome 10. It encodes a polypeptide, the {alpha}1(XVII) chain, consisting of an intracellular globular domain, a transmembrane segment, and an extracellular domain that contains 15 separate collagenous subdomains, the largest consisting of 242 amino acids. We also have developed a strategy to identify mutations in COL17A1 by use of PCR amplification of genomic DNA, using primers placed on the flanking introns. The PCR products are scanned for sequence variants by heteroduplex analysis using conformation-sensitive gel electrophoresis and then are subjected to direct automated sequencing. We have identified several intragenic polymorphisms in COL17A1, as well as mutations, in both alleles, in two Finnish families with GABEB. The probands in both families showed negative immunofluorescence staining with an anti-type XVII collagen antibody. In one family, the proband was homozygous for a 5-bp deletion, 2944del5, which resulted in frameshift and a premature termination codon of translation. The proband in the other family was a compound heterozygote, with one allele containing the 2944del5 mutation and the other containing a nonsense mutation, Q1023X. These results expand the mutation database in different variants of JEB, and they attest to the functional importance of type XVII collagen as a transmembrane component of the hemidesmosomes at the dermal/epidermal junction. 48 refs., 9 figs., 3 tabs.

  17. Toward molecular pathogenesis of an autoimmune disease: Refined genetic mapping of autoimmune polyglandular disease type I (APECED)

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, J.; Bjoerses, P.; Peltonen, L. [National Public Health Institute, Helsinki (Finland)] [and others

    1994-09-01

    Autoimmune reactions encoupled to many human diseases are still only partially understood. Unravelling the molecular pathogenesis of inherited diseases with a strong autoimmune component in their clinical expression could help to dissect individual components in the molecular background of abnormal immune response. One such genetic disorder is autosomal recessive autoimmune polyglandular disease type I (PGD I), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, MIM 240300). The disease is especially enriched in the genetically isolated population of Finland and we have assigned the APECED locus to human chromosome 21q22.3 in 14 Finnish families by linkage analyses. The best positional lod score of 6.49 was observed with marker D21S49. Based on the history of the Finns, the gene pool of this population clearly demonstrates the consequences of a founder effect and consequent isolation. In the Finnish population, we can take advantage of linkage disequilibrium and allelic association studies to more precisely define the critical DNA region for our disease gene of interest than would be possible by linkage analyses alone. We are now able to define the chromosomal region of interest between two flanking markers locating 1 cM apart. Linkage disequilibrium is observed with three of the markers used in the analyses and this suggests a distance of less than 500 kb to the disease locus, well approachable with molecular cloning techniques. Overlapping YAC and cosmid clones spanning our region of interest will facilitate the cloning of APECED gene in the near future.

  18. Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in the Japanese population.

    Directory of Open Access Journals (Sweden)

    Kiyoshi Migita

    Full Text Available BACKGROUND/AIMS: Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO AIH multicenter cohort study. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694. The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001, and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005. Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44 or without liver cirrhosis (n = 186 demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies. CONCLUSIONS/SIGNIFICANCE: This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.

  19. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

    Directory of Open Access Journals (Sweden)

    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  20. Screening markers for chronic atrophic gastritis in Chiapas, Mexico.

    Science.gov (United States)

    Ley, C; Mohar, A; Guarner, J; Herrera-Goepfert, R; Figueroa, L S; Halperin, D; Parsonnet, J

    2001-02-01

    Intestinal-type gastric adenocarcinomas usually are preceded by chronic atrophic gastritis. Studies of gastric cancer prevention often rely on identification of this condition. In a clinical trial, we sought to determine the best serological screening method for chronic atrophic gastritis and compared our findings to the published literature. Test characteristics of potential screening tests (antibodies to Helicobacter pyloni or CagA, elevated gastrin, low pepsinogen, increased age) alone or in combination were examined among consecutive subjects enrolled in a study of H. pylori and preneoplastic gastric lesions in Chiapas, Mexico; 70% had chronic atrophic gastritis. English-language articles concerning screening for chronic atrophic gastritis were also reviewed. Sensitivity for chronic atrophic gastritis was highest for antibodies to H. pylori (92%) or CagA, or gastrin levels >25 ng/l (both 83%). Specificity, however, was low for these tests (18, 41, and 22%, respectively). Pepsinogen levels were highly specific but insensitive markers of chronic atrophic gastritis (for pepsinogen I gastritis screening. However, no screening test was both highly sensitive and highly specific for chronic atrophic gastritis.

  1. Autoimmune hepatitis type 2 arising in PFAPA syndrome: coincidences or possible correlations?

    Science.gov (United States)

    Della Corte, Claudia; Ranucci, Giusy; Tufano, Maria; Alessio, Maria; Iorio, Raffaele

    2010-03-01

    PFAPA syndrome is a chronic disease classified in the group of autoinflammatory syndromes characterized by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis in young children. The etiology of this disorder is still unknown, but a primary dysfunction of the innate immune system seems to be involved. According to Marshall criteria, it is not possible to diagnose PFAPA in the presence of autoimmune diseases. We present here the case report of an 8-month girl with PFAPA who developed autoimmune hepatitis type 2 at the age of 18 months. We suppose that the dysregulation in innate immunity that is typical of patients with PFAPA could trigger autoimmune disorders such as autoimmune hepatitis in susceptible subjects. The possible relationships between immune-system dysfunction peculiar to this syndrome and autoimmune hepatitis are discussed.

  2. [Biermer's disease and autoimmune hemolytic anemia].

    Science.gov (United States)

    Nafil, Hatim; Tazi, Illias; Mahmal, Lahoucine

    2012-01-01

    Biermer's disease is an autoimmune atrophic gastritis of the fundus predominantly responsible for a malabsorption of vitamin B12. Despite its association with several autoimmune disorders, few observations have reported an association with autoimmune hemolytic anemia (AIHA). We report a case of Biermer's disease associated with AIHA in a patient of 66 years old.

  3. Type 1 Diabetes Mellitus Associated With Autoimmune Thyroid Disorders in Iranian Children: A Review

    Directory of Open Access Journals (Sweden)

    Daniel Zamanfar

    2015-01-01

    Full Text Available Context: Type one diabetes mellitus (T1DM is an autoimmune disorder that is yet the most common type of diabetes in children and adolescents. Several genetic risk factors have been associated with T1DM, auto immune thyroiditis and other autoimmune disorder. Among autoimmune disorders, autoimmune thyroid disease (ATD is the most frequent disorder associated with T1DM. Its prevalence varies depending on age, sex and ethnic origin of the subjects and is considerably higher than the general population and increases with duration of T1DM. The aim of this study was to review the prevalence of ATD in Iranian children with T1DM compared with other countries. Evidence Acquisition: We conducted a review on all papers published on the association between autoimmune thyroiditis and T1DM, which was available on Google Scholar, Scientific Information Database (SID, Magiran and Iran Medex databases up to June 2014. Both Persian and English articles were checked. The searched terms were: diabetes mellitus, autoimmune thyroiditis, prevalence, frequency, Iranian children and adolescents. All papers which were done on patients with age under 20 years old and have used Anti-TPO and Anti-TG to evaluate patients were included. Results: Six papers met all the criteria. A total of 736 participants were included in this review. After review of all the papers, the prevalence of Anti-TPO was reported between 8% and 30% and Anti-TG was reported 6.06% to 23.6% in diabetic children in Iran. Conclusions: Autoimmune thyroid disorders are the most prevalent immunological diseases in patients with type 1 diabetes. All these studies have shown a higher prevalence of the disorder in patients with T1DM compared to the Iranian healthy population. Anti-TPO reported between 8% and 30% and Anti-TG reported 6.06% to 23.6% in diabetic children in Iran that was similar to the studies in other countries.

  4. Autoimmune hepatitis

    Science.gov (United States)

    ... PA: Elsevier Saunders; 2010:chap 88. Read More Autoimmune disorders Chronic thyroiditis (Hashimoto disease) Cirrhosis Glomerulonephritis Hemolytic anemia Liver cancer - hepatocellular carcinoma Mesenteric venous thrombosis Type ...

  5. Late Diagnosed Type II Autoimmune Polyglandular Failure Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Mehtap Evran

    2014-03-01

    Full Text Available Autoimmune polyglandular syndrome (APS type II is the term descibing a group of diseases with two or more concurrent endocrine disorders. It is more prevalent in female gender. The most common pathologies include primary adrenal insufficiency (Addison’s disease, autoimmune thyroid diseases (Graves’ disease, Hashimoto’s thyroiditis, type 1 diabetes mellitus (DM and primary hypogonadism. Replacement of deficient hormone is the basis of treatment. The present paper discussed autoimmune polyglandular syndrome based on the symptoms in a 25-year-old female patient who was followed in the intensive care unit because of impaired consciousness considered to have resulted from potential drug/substance addiction. Antidepressant therapy was recommended for the patient and she was diagnosed with APS on further evaluation. Turk Jem 2014; 1: 13-16

  6. [Autoimmune hepatitis].

    Science.gov (United States)

    Ostojić, Rajko

    2003-01-01

    Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.

  7. Atrophic gastritis in young children and adolescents

    OpenAIRE

    Ricuarte, O; Gutierrez, O.; H. Cardona; Kim, J G; Graham, D Y; El-Zimaity, H M T

    2005-01-01

    Background: Helicobacter pylori associated gastric cancer arises via a multistage process, with atrophic gastritis being the precursor lesion. Helicobacter pylori is typically acquired in childhood, yet little is known of the prevalence of atrophic gastritis in childhood.

  8. Beta cell function and BMI in ethnically diverse children with newly diagnosed autoimmune type 1 diabetes

    Science.gov (United States)

    The objective of our study was to examine the relationship between BMI and beta-cell function at diagnosis of autoimmune type 1 diabetes (T1D) in a large group of ethnically diverse children. Cross-sectional analysis of 524 children (60.8% White, 19.5% Hispanic, 14.5% African-American, 5.2% other n...

  9. Republished: recent advances in autoimmune pancreatitis: type 1 and type 2.

    Science.gov (United States)

    Kamisawa, Terumi; Chari, Suresh T; Lerch, Markus M; Kim, Myung-Hwan; Gress, Thomas M; Shimosegawa, Tooru

    2014-01-01

    Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis characterised clinically by frequent presentation with obstructive jaundice, histologically by a lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response to steroids. When so defined, AIP can be sub-classified into two subtypes, 1 and 2. Recent international consensus diagnostic criteria for AIP have been developed for diagnosis of both forms of AIP. Type 1 AIP is the pancreatic manifestation of a multiorgan disease, recently named IgG4-related disease. Little is known about the pathogenesis of either form of AIP. Despite frequent association of type 1 AIP with elevated serum IgG4 levels and infiltration with IgG4-positive plasma cells, it is unlikely that IgG4 plays a pathogenic role in AIP. Type 1 AIP responds to steroids, but there needs to be consensus on treatment regimens for induction and therapeutic end points. Relapses are common, but can be reduced by long-term use of low-dose steroids. Recent reports suggest that immunomodulators (azathioprine, 6-mercaptopurine and mycophenolate mofetil), as well biological agents (the antibody to CD20, rituximab) may have a role in maintaining remission in relapsing type 1 AIP. Future studies should clarify the best management options for treatment of relapses and maintenance of remission. Type 2 AIP is a pancreas-specific disorder not associated with IgG4. It presents in younger individuals equally with obstructive jaundice and pancreatitis. The inflammatory process responds to steroid therapy; relapses are uncommon. The clinical spectrum and long-term outcomes of medically treated type 2 AIP are still being evaluated.

  10. Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes.

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    Irma Pujol-Autonell

    Full Text Available The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes.To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes.A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides.We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion.We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for

  11. PATHOGENETIC ROLE OF ABZYME-TYPE AUTOANTIBODIES IN THE ORGAN-SPECIFIC AUTOIMMUNE PATHOLOGY

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    L. N. Luchverchyk

    2011-01-01

    Full Text Available Abstract. The work deals with quantitative methods developed for estimation of nuclease and proteolytic activities  of  autoantibodies.  By  means  of  these  techniques,  appropriate  catalytic  activities  of  abzyme-type antibodies were studied in patients with diabetes mellitus type 1, and in subjects with autoimmune thyroiditis. Oppositely directed changes of the mentioned catalytic activities have been found for autoantibodies of different specificity.  Autoantibodies  occurring  in  autoimmune  thyroiditis  showed  an  increase  of  both  nuclease  and proteolytic activities. Meanwhile, the autoantibodies in diabetes mellitus had increased nuclease activity, along with decreased proteolytic activity. These findings are suggestive for existence of two pathogenetic mechanisms in organ-specific autoimmune pathology that are associated either with direct involvement of Fab fragments of auto-antibodies in autoimmune destruction, or with complement-dependent lysis mediated by Fc-fragments and  cytotoxic  destruction  of  target  cells  by  cytotoxic T-lymphocytes.  The  unique  site-specific  catalytic autoantibodies  were  established  to  exert  a  selective destructive effect upon target cells, thus making a major contribution to the antibody-dependent mechanisms of cytotoxicity in autoimmune diseases. (Med. Immunol., 2011, vol. 13, N 2-3, pp 145-150

  12. "PREVALENCE OF AUTOANTIBODIES TO THYROID PEROXIDASE AND AUTOIMMUNE THYROID DISEASE IN TYPE I DIABETES MELLITUS"

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    H. Moayeri A. Rabbani

    2004-09-01

    Full Text Available Type I diabetes mellitus (DM is frequently associated with autoimmune thyroid disease (ATD. Association of ATD and type I DM has been described with varying frequencies but there is still debate about the situation in the Iranian population. We investigated the prevalence of anti thyroid peroxidase (anti-TPO antibodies and ATD in children and adolescents with type I DM. A total of 145 patients with type I DM were participated in this study. They were screened for anti-TPO antibodies and TSH levels. Signs and symptoms of hypothyroidism and hyperthyroidism and the presence of goiter were sought. A group of 50 healthy unrelated girls and boys aged 11-16 years served as controls. Anti-TPO antibodies were found in 34 (23.4% diabetic patients and 1 subject (2% in the control group (P<0.001. Frequency of anti TPO antibodies was significantly higher in girls than boys (P<0.05. We failed to show any significant correlation between thyroid autoimmunity and duration of DM. We found that younger patients at diagnosis are more likely to be anti-TPO negative (P<0.001. Out of 145 diabetic patients, 32 (22% had visible goiter. Subclinical hypothyroidism, hypothyroidism and thyrotoxicosis occurred in 1, 9 and 1 patients, respectively. Visible goiter was found in 2 subjects (4% of the control group, but all of them were euthyroid. In conclusion, the evaluation of thyroid autoimmunity in type I diabetic patients may improve the diagnosis of thyroid disease in early stages. Yearly examination of anti-TPO antibodies allows identifying diabetic patients with thyroid autoimmunity.

  13. Primary prevention of beta-cell autoimmunity and type 1 diabetes – The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD perspectives

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    A.G. Ziegler

    2016-04-01

    Conclusion: It is timely and feasible to establish a platform for primary prevention trials for type 1 diabetes in Europe. This multi-site European infrastructure would perform RCTs, supply data coordination and biorepository, provide cohorts for mechanistic and observational studies, and increase awareness for autoimmune diabetes.

  14. Neurofibromatosis type 1 and autoimmune hyperthyroidism in a 10,5 years-old girl

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    Huseyin Demirbilek

    2013-08-01

    Full Text Available Neurofibromatosis type 1 (NF1 is an autosomal dominant inherited multisystem disease associated with several endocrine disorders. Association of NF1 and hyperthyroidism is extremely rare. All previously reported cases were in adult age group. Herein, we present autoimmune thyrotoxicosis associated to NF1 in a pediatric patient presenting with goiter and symptoms of thyrotoxicosis. [Cukurova Med J 2013; 38(4.000: 805-808

  15. [Chronic atrophic polychondritis and renal and cardiopulmonary amylosis: a case report and literature review (author's transl)].

    Science.gov (United States)

    Lambrozo, J; Baubion, D; Brodaty, Y; Leclerc, J P

    1981-01-01

    Glomerular lesions with a nephrotic syndrome and impaired renal function developed secondary to a chronic atrophic polychondritis confirmed by auricular biopsy. In the absence of renal histology data, the possibility of an iatrogenic complication or a renal lesion specific to the affection itself were successively eliminated. Pos-mortem histological examination demonstrated renal and cardiopulmonary amylosis, the latter being clinically asymptomatic. The probable autoimmune origin of the chronic atrophic polychondritis has to be discussed in parallel with the dysimmunity mechanism responsible for the amyloid lesions, but no relationship between them was demonstrated.

  16. Highly Effective New Treatments for Psoriasis Target the IL-23/Type 17 T Cell Autoimmune Axis.

    Science.gov (United States)

    Kim, Jaehwan; Krueger, James G

    2017-01-14

    Psoriasis vulgaris, affecting the skin, is one of the most common organ-specific autoimmune diseases in humans. Until recently, psoriasis was treated by agents or approaches discovered largely through serendipity. Many of the available drugs were inherently quite toxic when used as continuous treatment for many years in this chronic disease. However, an increasing understanding of disease-specific immune pathways has spurred development of pathway-targeted therapeutics during the past decade. Psoriasis is now the most effectively treated human autoimmune disease, with high-level clinical improvements possible in ∼90% of patients using a new generation of drugs that selectively target the IL-23/Type 17 T cell axis. Thus, psoriasis is a model for the success of a translational-medicine approach based on cellular and molecular dissection of disease pathogenesis in humans.

  17. Analysis of VH gene rearrangement and somatic hypermutation in type 1 autoimmune pancreatitis.

    Science.gov (United States)

    Okumura, Fumihiro; Sakuma, Hidenori; Nakazawa, Takahiro; Hayashi, Kazuki; Naitoh, Itaru; Miyabe, Katsuyuki; Yoshida, Michihiro; Yamashita, Hiroaki; Ohara, Hirotaka; Inagaki, Hiroshi; Joh, Takashi

    2012-05-01

    Type 1 autoimmune pancreatitis (AIP) is the pancreatic manifestation of systemic fibroinflammatory disease called immunoglobulin G4-associated systemic disease. Although this inflammatory process is considered to be a disease with an autoimmune mechanism, its pathogenesis still remains unclear. To clarify the characteristics of B cells infiltrating the lesion, we analyzed the immunoglobulin heavy chain variable region (VH) gene rearrangement and somatic hypermutation of invasive lymphoid cells in type 1 AIP (n= 3), in comparison with obstructive pancreatitis (n= 3) as a control. DNA was extracted from the affected inflammatory lesions. After PCR amplification of the rearranged VH gene, the clones were subcloned, and recombinant clones were randomly selected and sequenced. More than 60 clones per case were analyzed. Monoclonal VH rearrangement was not detected in any of the cases examined. There was no VH family or VH fragment specific to type 1 AIP and obstructive pancreatitis. However, the rate of unmutated VH fragments in type 1 AIP (17%) was higher than that in obstructive pancreatitis (5.1%) (P= 0.010). Our study suggests that an increased rate of unmutated or less mutated VH genes may be characteristic of type 1 AIP and might play a role in the development of this disease.

  18. Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases?

    Science.gov (United States)

    Tsai, Sue; Clemente-Casares, Xavier; Revelo, Xavier S; Winer, Shawn; Winer, Daniel A

    2015-06-01

    Obesity and associated insulin resistance predispose individuals to develop chronic metabolic diseases, such as type 2 diabetes and cardiovascular disease. Although these disorders affect a significant proportion of the global population, the underlying mechanisms of disease remain poorly understood. The discovery of elevated tumor necrosis factor-α in adipose tissue as an inducer of obesity-associated insulin resistance marked a new era of understanding that a subclinical inflammatory process underlies the insulin resistance and metabolic dysfunction that precedes type 2 diabetes. Advances in the field identified components of both the innate and adaptive immune response as key players in regulating such inflammatory processes. As antigen specificity is a hallmark of an adaptive immune response, its role in modulating the chronic inflammation that accompanies obesity and type 2 diabetes begs the question of whether insulin resistance and type 2 diabetes can have autoimmune components. In this Perspective, we summarize current data that pertain to the activation and perpetuation of adaptive immune responses during obesity and discuss key missing links and potential mechanisms for obesity-related insulin resistance and type 2 diabetes to be considered as potential autoimmune diseases.

  19. Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Aleksandra Krzewska

    2016-01-01

    Full Text Available Type 1 diabetes mellitus (T1DM is one of the most common chronic diseases developing in childhood. The incidence of the disease in children increases for unknown reasons at a rate from 3 to 5% every year worldwide. The background of T1DM is associated with the autoimmune process of pancreatic beta cell destruction, which leads to absolute insulin deficiency and organ damage. Complex interactions between environmental and genetic factors contribute to the development of T1DM in genetically predisposed patients. The T1DM-inducing autoimmune process can also affect other organs, resulting in development of additional autoimmune diseases in the patient, thereby impeding diabetes control. The most common T1DM comorbidities include autoimmune thyroid diseases, celiac disease, and autoimmune gastritis; additionally, diabetes can be a component of PAS (Polyglandular Autoimmune Syndrome. The aim of this review is to assess the prevalence of T1DM-associated autoimmune diseases in children and adolescents and their impact on the course of T1DM. We also present suggestions concerning screening tests.

  20. Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents

    Science.gov (United States)

    2016-01-01

    Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases developing in childhood. The incidence of the disease in children increases for unknown reasons at a rate from 3 to 5% every year worldwide. The background of T1DM is associated with the autoimmune process of pancreatic beta cell destruction, which leads to absolute insulin deficiency and organ damage. Complex interactions between environmental and genetic factors contribute to the development of T1DM in genetically predisposed patients. The T1DM-inducing autoimmune process can also affect other organs, resulting in development of additional autoimmune diseases in the patient, thereby impeding diabetes control. The most common T1DM comorbidities include autoimmune thyroid diseases, celiac disease, and autoimmune gastritis; additionally, diabetes can be a component of PAS (Polyglandular Autoimmune Syndrome). The aim of this review is to assess the prevalence of T1DM-associated autoimmune diseases in children and adolescents and their impact on the course of T1DM. We also present suggestions concerning screening tests. PMID:27525273

  1. Immunology in the Clinic Review Series; focus on metabolic diseases: development of islet autoimmune disease in type 2 diabetes patients: potential sequelae of chronic inflammation.

    Science.gov (United States)

    Brooks-Worrell, B; Palmer, J P

    2012-01-01

    Historically, the development of type 2 diabetes has been considered not to have an autoimmune component, in contrast to the autoimmune pathogenesis of type 1 diabetes. In this review we will discuss the accumulating data supporting the concept that islet autoreactivity and inflammation is present in type 2 diabetes pathogenesis, and the islet autoimmunity appears to be one of the factors associated with the progressive nature of the type 2 diabetes disease process.

  2. Ingested Type I Interferon—State of the Art as Treatment for Autoimmunity Part 2

    Directory of Open Access Journals (Sweden)

    Staley A. Brod

    2010-04-01

    Full Text Available We have proposed a unifying hypothesis of the etiopathogenesis of autoimmunity that defines autoimmunity as a type I interferon (IFN immunodeficiency syndrome. We have examined toxicity and potential efficacy in two phase I (type 1 diabetes [T1D], multiple sclerosis [MS] and phase II clinical trials in T1D and MS. In a phase I open label trial in T1D, ingested IFN-alpha preserved residual beta-cell function in recent onset patients. In a second phase I trial in MS, there was a significant decrease in peripheral blood mononuclear cell IL-2 and IFN-gamma production after ingesting IFN-alpha. In a phase II randomized, placebo-controlled, double-blind trial in MS, 10,000 IU ingested IFN-alpha significantly decreased gadolinium enhancements compared to the placebo group at month 5. TNF-alpha and IFN-gamma cytokine secretion in the 10,000 IU group at month 5 showed a significant decrease that corresponded with the effect of ingested IFN-alpha on decreasing gadolinium enhancements. In a phase II randomized, placebo-controlled, double-blind trial in T1D, patients in the 5,000 unit hrIFN-alpha treatment group maintained more beta-cell function one year after study enrollment compared to individuals in the placebo group. Ingested IFN-alpha was not toxic in these clinical trials. These studies suggest that ingested IFN-alpha may have a potential role in the treatment of autoimmunity.

  3. Individual behavioral characteristics of wild-type rats predict susceptibility to experimental autoimmune encephalomyelitis

    NARCIS (Netherlands)

    Kavelaars, A; Heijnen, CJ; Tennekes, R; Bruggink, JE; Koolhaas, JM; Heijnen, Cobi J.; Koolhaas, Jaap M.

    1999-01-01

    Neuroendocrine-immune interactions are thought to be important in determining susceptibility to autoimmune disease. Animal studies have revealed that differences in susceptibility to experimental autoimmune encephalomyelitis (EAE) are related to:reactivity in the hypothalamo-pituitary-adrenal axis.

  4. Histopathological Characteristics of Atrophic Gastritisin Adult Population

    Institute of Scientific and Technical Information of China (English)

    Marija Milicevic; Snezana Bozanic; Nenad Solajic

    2015-01-01

    Introduction: Chronic gastritis is inflammation of the gastric mucosa. It can be non-atrophic and atrophic. Atrophy isdefined as the loss of appropriate glands. It is frequently located in antral mucosa as consequence of Helicobacter pylori infectionand it is associated with intestinal gastric cancer. Goal: Describe histopathological and demographic characteristics of atrophicgastritis. Matherial and methods: We assessed the pathological reports of 100 patients with atrophic gastritis whose characteristicswere evaluated by using a semiquantitative scale of Sidney system of classification of gastritis. To assess the significance betweenthe incidence of various parametres we used ;~2 test. Results: We found that the difference in frequency of atrophic gastritis betweenmen and women was not statistically significant. The difference in distribution is statistically significant in favor of the antrum.Among patients who have atrophy with Helicobacterpylori infection and intestinal metaplasia and those who do not have metaplasia,it was found that the difference is highly statistically significant. Conclusion: The most frequent localisation of atrophic gastritis isantral mucosa. There is no difference between men and women in frequency of atrophic gastritis, while the aging is related with moreoften occurrence of atrophic gastritis.

  5. Type 1 diabetes: can exercise impair the autoimmune event? The L-arginine/glutamine coupling hypothesis.

    Science.gov (United States)

    Krause, Maurício da Silva; de Bittencourt, Paulo Ivo Homem

    2008-06-01

    Prevention of type 1 diabetes mellitus (T1DM) requires early intervention in the autoimmune process directed against beta-cells of the pancreatic islets of Langerhans, which is believed to result from a disorder of immunoregulation. According to this concept, a T-helper lymphocyte of type 1 (Th1) subset of T-lymphocytes and their cytokine products, the type 1 cytokines [e.g. interleukin 2 (IL-2), interferon gamma (IFN-gamma) and tumour necrosis factor beta (TNF-beta)] prevail over immunoregulatory (anti-inflammatory) Th2 subset and its cytokine products, i.e. type 2 cytokines (e.g. IL-4, IL-6 and IL-10). This allows type 1 cytokines to initiate a cascade of immune/inflammatory processes in the islet (insulitis), culminating in beta-cell destruction. Activation of sympathetic-corticotropin-releasing hormone (CRH) axis by psychological stress induces specifically Th1 cell overactivity that determines enhanced glutamine utilization and consequent poor L-arginine supply for nitric oxide (NO)-assisted insulin secretion. This determines the shift of intraislet glutamate metabolism from the synthesis of glutathione (GSH) to that of L-arginine, leading to a redox imbalance that activates nuclear factor kappaB exacerbating inflammation and NO-mediated cytotoxicity. Physical exercise is capable of inducing changes in the pattern of cytokine production and release towards type 2 class and to normalize the glutamine supply to the circulation, which reduces the need for glutamate, whose metabolic fate may be restored in the direction of GSH synthesis and antioxidant defence. Also, the 70-kDa heat shock protein (hsp70), which is immunoregulatory, may modulate exercise-induced anti-inflammation. In this work, we envisage how exercise can intervene in the mechanisms involved in the autoimmune process against beta-cells and how novel therapeutic approaches may be inferred from these observations.

  6. Thyroid Autoimmunity and Gluten-Sensitive Enteropathy in Children with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Gafur Doğdu

    2012-06-01

    Full Text Available Introduction: To determine the seroprevalence of autoimmune thyroiditis and gluten-sensitive enteropathy (GSE in patients with type 1 diabetes mellitus (T1DM and to emphasize the importance of early diagnosis. Patients and Methods: Fifty-five children and adolescents (age ranged 3-18 years with T1DM were included in the study. Hemoglobin A1c (HbA1c, free T3 (fT3, free T4 (fT4, thyroid stimulating hormone (TSH, anti-tiroglobulin (anti-TG, anti-thyroid peroxidase (anti-TPO, anti-gliadin IgA and IgG, and anti-endomisyum IgA antibody (antiEMA were investigated. Results: Eight of our cases (14.5% were positive for anti-TPO, 9/55 (16.3% for anti-TG, 8/55 (14.5% for anti-EMA, 8/55 (14.5% for anti-gliadin IgA, and 5/55 (9.0% for anti-gliadin IgG. None of these antibodies were detected in healthy controls. In eight patients, who had positive anti-TPO and anti-TG, thyroid ultrasound results confirmed thyroiditis. Anti-EMA and anti-gliadin IgA were positive in five patients. Four of them were diagnosed with GSE. Conclusion: In patients with T1DM, the seroprevalences of autoimmune thyroiditis and GSE were higher than that in healthy controls. Therefore, regardless of the symptoms of patients, autoimmune thyroiditis and GSE should be investigated in all patients with T1DM. Thus, the most rapid and meaningful method is to investigate the presence of autoantibodies using serological tests. (The Me di cal Bul le tin of Ha se ki 2012; 50: 39-42

  7. Autoimmun pankreatitis

    DEFF Research Database (Denmark)

    Fjordside, Eva; Novovic, Srdan; Schmidt, Palle Nordblad;

    2015-01-01

    Autoimmune pancreatitis (AIP) is a rare inflammatory disease. AIP has characteristic histology, serology and imaging findings. Two types of AIP exist, type 1, which is a part of the systemic immunoglobulin G4-related disease, and type 2, which is only localized to the pancreas. Patients with type 1...... are predominantly older men, have involvement of other organs and more often experience relapse than patients with type 2. Both types respond well to steroid treatment. The most important differential diagnose is pancreatic cancer....

  8. Helicobacter pylori infection might be responsible for the interconnection between type 1 diabetes and autoimmune thyroiditis

    Directory of Open Access Journals (Sweden)

    El-Eshmawy Mervat M

    2011-10-01

    Full Text Available Abstract Background Higher serological prevalence rates of helicobacter pylori (H. pylori infection have been reported in patients with type 1 diabetes (T1DM and autoimmune thyroiditis (AT. Patients with T1DM are at increased risk for developing other autoimmune diseases, most commonly AT. It is unknown whether H. pylori infection could explain the high prevalence of thyroid autoantibodies and AT in T1DM. The aim of the current study was to evaluate anti-thyroid peroxidase (anti-TPO and anti-thyroglobulin (anti-Tg autoantibodies in correlation with anti-H. pylori IgG and IgA in young patients with T1DM. Methods Anti-H. Pylori IgG, IgA, anti-TPO and anti-Tg antibodies titers were measured in 162 euthyroid patients with T1DM and 80 healthy controls matched for age, sex and socioeconomic status. Results Seroprevalence of H. pylori was significantly higher in patients with T1DM than in healthy controls; 79% vs. 51.2%, p Conclusion our results support the idea of a connection between H. pylori infection and the occurrence of anti-TPO, anti-Tg autoantibodies and AT in young patients with T1DM. So, H. pylori infection could be considered as an environmental trigger for development of AT in T1DM. Young patients with T1DM should be screened for H. pylori infection.

  9. [Drug-induced exacerbation of hypoaldosteronism in autoimmune polyglandular syndrome type 2].

    Science.gov (United States)

    Krysiak, Robert; Okopień, Bogusław

    2012-01-01

    Hypoaldosteronism is a clinical condition resulting from inadequate stimulation of aIdosterone secretion (hyporeninemic hypoaIdosteronism), defects in adrenal synthesis of aldosterone (hyperreninemic hypoaldosteronism), or resistance to the peripheral action of this hormone (pseudohypoaldosteronism). The disease is characterized by a wide spectrum of clinical manifestations, ranging from asymptomatic hyperkalemia to life-threatening volume depletion, and, if unrecognized and untreated, it increases morbidity and mortality rates. In this paper, we report a case of a woman diagnosed with autoimmune polyglandular syndrome type 2. As a consequence of adrenal cortex destruction, the patient developed subclinical hypoaldosteronism which was effectively treated with small doses of fludrocortisone. Two and fours years later, she required ibuprofen and atenolol treatment and each of these treatments was accompanied by a transient deterioration in mineralocorticoid activity which resolved after drug withdrawal. This case shows for the first time that drugs reducing plasma renin activity may unmask subclinical hypoaldosteronism in subjects with autoimmune polyglandular syndromes, and that they should be avoided in patients with even small disturbances in the hormonal function of the zona glomerulosa.

  10. A functional alternative splicing mutation in AIRE gene causes autoimmune polyendocrine syndrome type 1.

    Directory of Open Access Journals (Sweden)

    Junyu Zhang

    Full Text Available Autoimmune polyendocrine syndrome type 1 (APS-1 is a rare autosomal recessive disease defined by the presence of two of the three conditions: mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Loss-of-function mutations of the autoimmune regulator (AIRE gene have been linked to APS-1. Here we report mutational analysis and functional characterization of an AIRE mutation in a consanguineous Chinese family with APS-1. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. We identified a homozygous missense AIRE mutation c.463G>A (p.Gly155Ser in two siblings with different clinical features of APS-1. In silico splice-site prediction and minigene analysis were carried out to study the potential pathological consequence. Minigene splicing analysis and subsequent cDNA sequencing revealed that the AIRE mutation potentially compromised the recognition of the splice donor of intron 3, causing alternative pre-mRNA splicing by intron 3 retention. Furthermore, the aberrant AIRE transcript was identified in a heterozygous carrier of the c.463G>A mutation. The aberrant intron 3-retaining transcript generated a truncated protein (p.G155fsX203 containing the first 154 AIRE amino acids and followed by 48 aberrant amino acids. Therefore, our study represents the first functional characterization of the alternatively spliced AIRE mutation that may explain the pathogenetic role in APS-1.

  11. Quantification of scar margin in keloid different from atrophic scar by multiphoton microscopic imaging.

    Science.gov (United States)

    Zhu, Xiaoqin; Zhuo, Shuangmu; Zheng, Liqin; Jiang, Xingshan; Chen, Jianxin; Lin, Bifang

    2011-01-01

    Multiphoton microscopy (MPM) was applied to examine the marginal region at dermis of keloid compared with atrophic scar. High-resolution large-area image showed an obvious boundary at the scar margin and different morphological patterns of elastin and collagen on the two sides, further visualized by the focused three-dimensional images. Content alteration of elastin or collagen between the two sides of boundary was quantified to show significant difference between keloid and atrophic scar. Owing to the raised property of keloid with overproduced collagen on the scar side, the content alteration was positive for elastin and negative for collagen. On the contrary, the content alteration was negative for elastin and positive for collagen in the atrophic scar case due to the atrophic collagen on the scar side. It indicated that examination of the scar margin by MPM may lead a new way to discriminate different types of scars and better understand the scarring mechanisms.

  12. Primary Dietary Intervention Study to Reduce the Risk of Islet Autoimmunity in Children at Increased Risk for Type 1 Diabetes

    OpenAIRE

    Hummel, Sandra; Pflüger, Maren; Hummel, Michael; Bonifacio, Ezio; Ziegler, Anette-G.

    2011-01-01

    OBJECTIVE To determine whether delaying the introduction of gluten in infants with a genetic risk of islet autoimmunity is feasible, safe, and may reduce the risk of type 1 diabetes–associated islet autoimmunity. RESEARCH DESIGN AND METHODS A total of 150 infants with a first-degree family history of type 1 diabetes and a risk HLA genotype were randomly assigned to a first gluten exposure at age 6 months (control group) or 12 months (late-exposure group) and were followed 3 monthly until the ...

  13. Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes.

    Directory of Open Access Journals (Sweden)

    Thomas B Thornley

    Full Text Available The innate immune system critically shapes diabetogenic adaptive immunity during type 1 diabetes (T1D pathogenesis. While the role of tissue-infiltrating monocyte-derived macrophages in T1D is well established, the role of their tissue-resident counterparts remains undefined. We now demonstrate that islet resident macrophages (IRMs from non-autoimmune mice have an immunoregulatory phenotype and powerfully induce FoxP3+ Tregs in vitro. The immunoregulatory phenotype and function of IRMs is compromised by TLR4 activation in vitro. Moreover, as T1D approaches in NOD mice, the immunoregulatory phenotype of IRMs is diminished as is their relative abundance compared to immunostimulatory DCs. Our findings suggest that maintenance of IRM abundance and their immunoregulatory phenotype may constitute a novel therapeutic strategy to prevent and/or cure T1D.

  14. Prevalence of celiac disease autoimmunity in children with type 1 diabetes

    DEFF Research Database (Denmark)

    Adlercreutz, Emma H; Svensson, Jannet; Hansen, Dorthe

    2015-01-01

    OBJECTIVES: The aim was to determine the prevalence of celiac disease autoimmunity in children with type 1 diabetes (T1D) diagnosed in Denmark and Sweden. METHODS: A total of 662 Swedish children with T1D were matched with 1080 Danish children with T1D and 309 healthy children from Sweden and 283...... was equally distributed among 89 children with T1D positive for both IgAG-DGP/tTG and IgG-tTG. CONCLUSION: The discrepancy in levels of IgAG-DGP/tTG and IgG-tTG between Swedish and Danish T1D cohorts was independent of HLA and suggests that regional variations in comorbidity of celiac disease in T1D is caused...

  15. Lessons From Pancreas Transplantation in Type 1 Diabetes: Recurrence of Islet Autoimmunity.

    Science.gov (United States)

    Burke, George W; Vendrame, Francesco; Virdi, Sahil K; Ciancio, G; Chen, Linda; Ruiz, Phillip; Messinger, Shari; Reijonen, Helena K; Pugliese, Alberto

    2015-12-01

    Type 1 diabetes recurrence (T1DR) affecting pancreas transplants was first reported in recipients of living-related pancreas grafts from twins or HLA identical siblings; given HLA identity, recipients received no or minimal immunosuppression. This observation provided critical evidence that type 1 diabetes (T1D) is an autoimmune disease. However, T1DR is traditionally considered very rare in immunosuppressed recipients of pancreas grafts from organ donors, representing the majority of recipients, and immunological graft failures are ascribed to chronic rejection. We have been performing simultaneous pancreas-kidney (SPK) transplants for over 25 years and find that 6-8 % of our recipients develop T1DR, with symptoms usually becoming manifest on extended follow-up. T1DR is typically characterized by (1) variable degree of insulitis and loss of insulin staining, on pancreas transplant biopsy (with most often absent), minimal to moderate and rarely severe pancreas, and/or kidney transplant rejection; (2) the conversion of T1D-associated autoantibodies (to the autoantigens GAD65, IA-2, and ZnT8), preceding hyperglycemia by a variable length of time; and (3) the presence of autoreactive T cells in the peripheral blood, pancreas transplant, and/or peripancreatic transplant lymph nodes. There is no therapeutic regimen that so far has controlled the progression of islet autoimmunity, even when additional immunosuppression was added to the ongoing chronic regimens; we hope that further studies and, in particular, in-depth analysis of pancreas transplant biopsies with recurrent diabetes will help identify more effective therapeutic approaches.

  16. Association of type 1 diabetes mellitus and autoimmune disorders in Brazilian children and adolescents

    Directory of Open Access Journals (Sweden)

    Crésio Alves

    2016-01-01

    Full Text Available Context: Type 1 diabetes mellitus (T1DM is caused by an immune-mediated destruction of pancreatic beta cells. Other autoimmune diseases can be observed in association with T1DM. The screening for celiac disease (CD and Hashimoto's thyroiditis is necessary due to the increased prevalence of these pathologies in T1DM patients. Aims: This study aimed to investigate the prevalence of autoimmune markers for pancreatitis, thyroiditis, and CD in racially admixtured children and adolescents with T1DM. Settings and Design: Cross-sectional clinic-based study. Methods: Seventy-one patients with T1DM (average: 11.6 ± 5.1 years. In all patients, the following antibodies were surveyed: Anti-glutamic acid decarboxylase (anti-GAD, immunoglobulin A (IgA anti-transglutaminase (anti-tTG, Antithyroglobulin (AAT, anti-thyroid peroxidase (anti-TPO, and IgA. Statistical Analysis Used: The quantitative variables were expressed as a mean and standard deviation and the qualitative variables in contingency tables. Student's t-test and χ2 tests were used to assess the differences between the groups. The level of significance was established as P < 0.05. Results: The prevalence of anti-GAD antibodies was 5.9%; anti-tTG IgA, 7.4%; anti-TPO, 11.8%; and AAT, 11.8%. Conclusions: Children and adolescents with T1DM have increased the prevalence of antithyroid and CD-related antibodies. The positivity for anti-GAD and antithyroid antibodies was less frequent than in other studies. The prevalence of anti-tTG antibodies was similar to the literature.

  17. New splice site acceptor mutation in AIRE gene in autoimmune polyendocrine syndrome type 1.

    Directory of Open Access Journals (Sweden)

    Mireia Mora

    Full Text Available Autoimmune polyglandular syndrome type 1 (APS-1, OMIM 240300 is a rare autosomal recessive disorder, characterized by the presence of at least two of three major diseases: hypoparathyroidism, Addison's disease, and chronic mucocutaneous candidiasis. We aim to identify the molecular defects and investigate the clinical and mutational characteristics in an index case and other members of a consanguineous family. We identified a novel homozygous mutation in the splice site acceptor (SSA of intron 5 (c.653-1G>A in two siblings with different clinical outcomes of APS-1. Coding DNA sequencing revealed that this AIRE mutation potentially compromised the recognition of the constitutive SSA of intron 5, splicing upstream onto a nearby cryptic SSA in intron 5. Surprisingly, the use of an alternative SSA entails the uncovering of a cryptic donor splice site in exon 5. This new transcript generates a truncated protein (p.A214fs67X containing the first 213 amino acids and followed by 68 aberrant amino acids. The mutation affects the proper splicing, not only at the acceptor but also at the donor splice site, highlighting the complexity of recognizing suitable splicing sites and the importance of sequencing the intron-exon junctions for a more precise molecular diagnosis and correct genetic counseling. As both siblings were carrying the same mutation but exhibited a different APS-1 onset, and one of the brothers was not clinically diagnosed, our finding highlights the possibility to suspect mutations in the AIRE gene in cases of childhood chronic candidiasis and/or hypoparathyroidism otherwise unexplained, especially when the phenotype is associated with other autoimmune diseases.

  18. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases.

    Science.gov (United States)

    Schwartz, Daniella M; Bonelli, Michael; Gadina, Massimo; O'Shea, John J

    2016-01-01

    Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Despite the effectiveness of these drugs, they do not induce complete remission in all patients, prompting the development of alternative strategies - including targeting of intracellular signal transduction pathways downstream of cytokines. Many cytokines that bind type I and type II cytokine receptors are critical regulators of immune-mediated diseases and employ the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway to exert their effect. Pharmacological inhibition of JAKs blocks the actions of type I/II cytokines, and within the past 3 years therapeutic JAK inhibitors, or Jakinibs, have become available to rheumatologists. Jakinibs have proven effective for the treatment of rheumatoid arthritis and other inflammatory diseases. Adverse effects of these agents are largely related to their mode of action and include infections and hyperlipidemia. Jakinibs are currently being investigated for a number of new indications, and second-generation selective Jakinibs are being developed and tested. Targeting STATs could be a future avenue for the treatment of rheumatologic diseases, although substantial challenges remain. Nonetheless, the ability to therapeutically target intracellular signalling pathways has already created a new paradigm for the treatment of rheumatologic disease.

  19. Early infant feeding and risk of developing islet autoimmunity and type 1 diabetes.

    Science.gov (United States)

    Chmiel, Ruth; Beyerlein, Andreas; Knopff, Annette; Hummel, Sandra; Ziegler, Anette-G; Winkler, Christiane

    2015-06-01

    We investigated whether food supplementation within the first year life or age at introduction of gluten-containing foods influenced the risk of developing islet autoimmunity and type 1 diabetes. A total of 2,291 children with a family history of type 1 diabetes were prospectively followed from birth for 28,983 patient years (median 13.1 years). Dietary exposure data were collected by questionnaires, food records and by family interview. Exposure to gluten-containing foods before age 3 months, which occurred in 19 children, increased the risk of developing islet autoantibodies (n = 4), multiple islet autoantibodies (n = 4), and type 1 diabetes (n = 3) compared to exclusive breastfeeding within the first 3 months [adjusted hazard ratio (HR) 3.97 (95 % confidence interval 1.41-11.17), 5.39 (1.89-15.35), and 3.45 (1.04-11.48), respectively] and also compared to first exposure to gluten between 3.1 and 6.0 months of age [adjusted HR 3.40 (1.19-9.70), 4.25 (1.47-12.26), and 3.43 (1.01-11.66), respectively]. Children who received infant formula or other solid food within the first 3 months and children who received gluten-containing foods after age 6 months did not have an increased risk of islet autoantibodies, multiple islet autoantibodies or type 1 diabetes. Our present data affirm that compliance to infant feeding guidelines is a possible way to reduce type 1 diabetes risk in genetically susceptible children.

  20. The Contribution of Immune and Glial Cell Types in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Samuel S. Duffy

    2014-01-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the central nervous system characterised by widespread areas of focal demyelination. Its aetiology and pathogenesis remain unclear despite substantial insights gained through studies of animal models, most notably experimental autoimmune encephalomyelitis (EAE. MS is widely believed to be immune-mediated and pathologically attributable to myelin-specific autoreactive CD4+ T cells. In recent years, MS research has expanded beyond its focus on CD4+ T cells to recognise the contributions of multiple immune and glial cell types to the development, progression, and amelioration of the disease. This review summarises evidence of T and B lymphocyte, natural killer cell, macrophage/microglial, astrocytic, and oligodendroglial involvement in both EAE and MS and the intercommunication and influence of each cell subset in the inflammatory process. Despite important advances in the understanding of the involvement of these cell types in MS, many questions still remain regarding the various subsets within each cell population and their exact contribution to different stages of the disease.

  1. Effects of Different Measures of Recovery on the Fiber Types of Atrophic Muscle in Rats%不同恢复方式对去负荷大鼠腓肠肌纤维类型组成的影响

    Institute of Scientific and Technical Information of China (English)

    吴金富; 周越; 王兵; 许寿生

    2011-01-01

    Objective To observe the effects of eccentric exercise on the atrophic gastrocnemius and its fibre types induced by simulated weightlessness. Methods Thirty female Sprague-Dawley rats were randomly assigned to four groups: control group (CON, n = 6) , two-week tail-suspension group (TS, n = 6) > two-week tail-suspension following two-week normal rehabilitation group (NR, n = 6) , two-week tail-suspension following two-week eccentric exercise rehabilitation group (ER, n = 6) . The eccentric exercise was executed through downhill running with the slope of 5% at the speed of 16m/min. Gastrocnemius were sectioned with cryostat and stained with ATPase. The cross sectional area (CSA) and the proportion of type I, Ha, and IIb fibers were measured using Leica image analysis system. Results In group TS, wet weights of the gastrocnemius, CSA of type I and IIb fibers, and proportion of type I and IIa fibers decreased obviously, as compared with that in group CON (P<0.01) . The proportion of type IIb fiber increased significantly as compared with that in group CON (P < 0.01) . CSA and proportion of type I, II and IIb fibers after eccentric exercise became normal (P<0.01) ,and the proportion of type I in group NR only restored to normal level. Conclusion Eccentric exercise training fully promoted the recovering of CSA and relative proportion of type I, IIa, and IIb fibers in atrophic gastrocnemius induced by simulated weightlessness in rats.%目的:探讨自然恢复和离心运动恢复等再负荷方式对废用性骨骼肌纤维横截面积及类型的影响.方法:采用尾部悬吊模型.24只成年雌性SD大鼠按体重随机分为对照组(CON)、尾部悬吊组(TS),悬吊14天后解悬吊自然恢复组(NR)和悬吊14天后离心运动恢复组(ER),每组6只.离心运动为每天下坡跑1h,坡度-5%,跑速16 m/min,共2周.取大鼠腓肠肌进行异染性染料ATPase染色,计算腓肠肌纤维组成百分比和肌纤维横截面积(CSA).结果:(1) TS组大鼠腓

  2. GAD65 autoantibodies and its role as biomarker of Type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA)

    OpenAIRE

    Towns, Roberto; Pietropaolo, Massimo

    2011-01-01

    One of the hallmarks of autoimmune diabetes is the presence of adaptive responses directed to neuroendocrine proteins. One of these proteins is glutamic acid decarboxylase (GAD). While GAD is widely distributed in neuroendocrine tissues, its specific significance in diabetes has paralleled the advances in understanding humoral and cellular immunity in Type 1 diabetes (T1D) and in a subset of Type 2 diabetes (T2D), going from the seminal discoveries of islet autoantibodies to the development a...

  3. Effects of Non-HLA Gene Polymorphisms on Development of Islet Autoimmunity and Type 1 Diabetes in a Population With High-Risk HLA-DR,DQ Genotypes

    NARCIS (Netherlands)

    Steck, Andrea K.; Wong, Randall; Wagner, Brandie; Johnson, Kelly; Liu, Edwin; Romanos, Jihane; Wijmenga, Cisca; Norris, Jill M.; Eisenbarth, George S.; Rewers, Marian J.

    2012-01-01

    We assessed the effects of non-HLA gene polymorphisms on the risk of islet autoimmunity (IA) and progression to type 1 diabetes in the Diabetes Autoimmunity Study in the Young. A total of 1,743 non-Hispanic, white children were included: 861 first-degree relatives and 882 general population children

  4. Doubly Reactive INS-IGF2 Autoantibodies in Children with Newly Diagnosed Autoimmune (type 1) Diabetes.

    Science.gov (United States)

    Kanatsuna, N; Delli, A; Andersson, C; Nilsson, A-L; Vaziri-Sani, F; Larsson, K; Carlsson, A; Cedervall, E; Jönsson, B; Neiderud, J; Elding Larsson, H; Ivarsson, S-A; Törn, C; Fex, M; Lernmark, Å

    2015-10-01

    The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P INS-IGF2A when the cut-off was the 95th percentile of the controls (P INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.

  5. Neutralization Versus Reinforcement of Proinflammatory Cytokines to Arrest Autoimmunity in Type 1 Diabetes.

    Science.gov (United States)

    Kaminitz, Ayelet; Ash, Shifra; Askenasy, Nadir

    2016-09-27

    As physiological pathways of intercellular communication produced by all cells, cytokines are involved in the pathogenesis of inflammatory insulitis as well as pivotal mediators of immune homeostasis. Proinflammatory cytokines including interleukins, interferons, transforming growth factor-β, tumor necrosis factor-α, and nitric oxide promote destructive insulitis in type 1 diabetes through amplification of the autoimmune reaction, direct toxicity to β-cells, and sensitization of islets to apoptosis. The concept that neutralization of cytokines may be of therapeutic benefit has been tested in few clinical studies, which fell short of inducing sustained remission or achieving disease arrest. Therapeutic failure is explained by the redundant activities of individual cytokines and their combinations, which are rather dispensable in the process of destructive insulitis because other cytolytic pathways efficiently compensate their deficiency. Proinflammatory cytokines are less redundant in regulation of the inflammatory reaction, displaying protective effects through restriction of effector cell activity, reinforcement of suppressor cell function, and participation in islet recovery from injury. Our analysis suggests that the role of cytokines in immune homeostasis overrides their contribution to β-cell death and may be used as potent immunomodulatory agents for therapeutic purposes rather than neutralized.

  6. A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis

    Science.gov (United States)

    Lund, Maria E.; Greer, Judith; Dixit, Aakanksha; Alvarado, Raquel; McCauley-Winter, Padraig; To, Joyce; Tanaka, Akane; Hutchinson, Andrew T.; Robinson, Mark W.; Simpson, Ann M.; O’Brien, Bronwyn A.; Dalton, John P.; Donnelly, Sheila

    2016-01-01

    Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases. PMID:27883079

  7. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report

    Directory of Open Access Journals (Sweden)

    Bonilla-Abadía Fabio

    2012-12-01

    Full Text Available Abstract Background The localized scleroderma (LS known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case presentation We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Conclusion Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.

  8. Deep vein thrombosis, an unreported first manifestation of polyglandular autoimmune syndrome type III

    Science.gov (United States)

    Hogan, P; Oliver, T

    2016-01-01

    Summary A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT) confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA), confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL), decreased serum B12 levels (56pg/mL), with resultant increased methylmalonic acid (5303nmol/L) and hyperhomocysteinemia (131μmol/L), the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD), and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B), defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases. Learning points A DVT can be the first physical manifestation of a polyglandular autoimmune syndrome. Hyperhomocysteinemia secondary to pernicious anemia should be considered as an etiology of an unprovoked DVT in a euthyroid patient with autoimmune thyroid disease. Patients with DVT secondary to hyperhomocysteinemia should undergo screening for the presence of co-existent autoimmune diseases in addition to treatment with B12 supplementation and anticoagulation to prevent recurrent thromboembolism. PMID:27482386

  9. Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity

    Directory of Open Access Journals (Sweden)

    Di eFeng

    2013-09-01

    Full Text Available Patients with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS display increased levels of type I IFN-induced genes. Plasmacytoid dendritic cells (PDCs are natural interferon producing cells and considered to be a primary source of IFN-α in these two diseases. Differential expression patterns of type I IFN inducible transcripts can be found in different immune cell subsets and in patients with both active and inactive autoimmune disease. A type I IFN gene signature generally consists of three groups of IFN-induced genes - those regulated in response to virus-induced type I IFN, those regulated by the IFN-induced mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK pathway, and those by the IFN-induced phosphoinositide-3 kinase (PI-3K pathway. These three groups of type I IFN-regulated genes control important cellular processes such as apoptosis, survival, adhesion, and chemotaxis, that when dysregulated, contribute to autoimmunity. With the recent generation of large datasets in the public domain from next-generation sequencing and DNA microarray experiments, one can perform detailed analyses of cell type-specific gene signatures as well as identify distinct transcription factors that differentially regulate these gene signatures. We have performed bioinformatics analysis of data in the public domain and experimental data from our lab to gain insight into the regulation of type I IFN gene expression. We have found that the genetic landscape of the IFNA and IFNB genes are occupied by transcription factors, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as IRF5 and IRF7, that positively and distinctly regulate IFNA subtypes. A detailed understanding of the factors controlling type I IFN gene transcription will significantly aid in the identification and development of new therapeutic strategies targeting the IFN pathway in autoimmune disease.

  10. Circulating microRNA Profiles in Patients with Type-1 Autoimmune Hepatitis.

    Directory of Open Access Journals (Sweden)

    Kiyoshi Migita

    Full Text Available Recent studies have demonstrated that micro (miRNA molecules can be detected in the circulation and can serve as potential biomarkers of various diseases. This study used microarray analysis to identify aberrantly expressed circulating miRNAs in patients with type 1 autoimmune hepatitis (AIH compared with healthy controls. Patients with well-documented and untreated AIH were selected from the National Hospital Organization (NHO-AIH-liver-network database. They underwent blood sampling and liver biopsy with inflammation grading and fibrosis staging before receiving treatment. To further confirm the microarray data, circulating expression levels of miR-21 and miR-122 were quantified by real-time quantitative polymerase chain reaction in 46 AIH patients, 40 patients with chronic hepatitis C (CHC, and 13 healthy controls. Consistent with the microarray data, serum levels of miR-21 were significantly elevated in AIH patients compared with CHC patients and healthy controls. miR-21 and miR-122 serum levels correlated with alanine aminotransferase levels. Circulating levels of miR-21 and miR-122 were significantly reduced in AIH patients with liver cirrhosis, and were inversely correlated with increased stages of fibrosis. By contrast, levels of circulating miR-21 showed a significant correlation with the histological grades of inflammation in AIH. We postulate that aberrantly expressed serum miRNAs are potential biomarkers of AIH and could be implicated in AIH pathogenesis. Alternations of miR-21 and miR-122 serum levels could reflect their putative roles in the mediation of inflammatory processes in AIH.

  11. Cardiac tamponade due to low-volume effusive constrictive pericarditis in a patient with uncontrolled type II autoimmune polyglandular syndrome.

    Science.gov (United States)

    Palmer, William C; Kurklinsky, Andrew; Lane, Gary; Ussavarungsi, Kamonpun; Blackshear, Joseph L

    2014-03-01

    Type II autoimmune polyglandular syndrome (APS), a relatively common endocrine disorder, includes primary adrenal insufficiency coupled with type 1 diabetes mellitus and/or autoimmune primary hypothyroidism. Autoimmune serositis, an associated disease, may present as symptomatic pericardial effusion. We present a case of a 54-year old male with APS who developed pericarditis leading to cardiac tamponade with a subacute loculated effusion. After urgent pericardiocentesis intrapericardial pressure dropped to 0, while central venous pressures remain elevated, consistent with acute effusive constrictive pericarditis. Contrast computerized tomography confirmed increased pericardial contrast enhancement. The patient recovered after prolonged inotropic support and glucocorticoid administration. He re-accumulated the effusion 16 days later, requiring repeat pericardiocentesis. Effusive-constrictive pericarditis, an uncommon pericardial syndrome, is characterized by simultaneous pericardial inflammation and tamponade. Prior cases of APS associated with cardiac tamponade despite low volumes of effusion have been reported, albeit without good demonstration of hemodynamic findings. We report a case of APS with recurrent pericardial effusion due to pericarditis and marked hypotension with comprehensive clinical and hemodynamic assessment. These patients may require aggressive support with pericardiocentesis, inotropes, and hormone replacement therapy. They should be followed closely for recurrent tamponade.

  12. Deep vein thrombosis, an unreported first manifestation of polyglandular autoimmune syndrome type III

    Directory of Open Access Journals (Sweden)

    M Horsey

    2016-07-01

    Full Text Available A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA, confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL, decreased serum B12 levels (56pg/mL, with resultant increased methylmalonic acid (5303nmol/L and hyperhomocysteinemia (131μmol/L, the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD, and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B, defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases.

  13. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes

    NARCIS (Netherlands)

    Magitta, N. F.; Wolff, A. S. Boe; Johansson, S.; Skinningsrud, B.; Lie, B. A.; Myhr, K-M; Undlien, D. E.; Joner, G.; Njolstad, P. R.; Kvien, T. K.; Forre, O.; Knappskog, P. M.; Husebye, E. S.

    2009-01-01

    Variants in the gene encoding NACHT leucine-rich-repeat protein 1 (NALP1), an important molecule in innate immunity, have recently been shown to confer risk for vitiligo and associated autoimmunity. We hypothesized that sequence variants in this gene may be involved in susceptibility to a wider spec

  14. The role of dendritic cell subsets and innate immunity in the pathogenesis of type 1 diabetes and other autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Jeffrey D. Price

    2015-06-01

    Full Text Available Dendritic cells (DCs are key antigen presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are 4 main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in autoimmune pathogenesis and regulation, as well as the genetic and environmental signals that influence their function. Specific topics to be addressed include: impact of susceptibility loci on DC subsets, alterations in DC subset development, the role of infection- and host-derived innate inflammatory signals, and the role of the intestinal microbiota on DC phenotype. The effects of these various signals on disease progression and the relative effects of DC subset composition and maturation level of DCs will be examined. These areas will be explored using examples from several autoimmune diseases but will focus mainly on type 1 diabetes.

  15. Diagnosis of autoimmune gastritis by high resolution magnification endoscopy

    Institute of Scientific and Technical Information of China (English)

    George K Anagnostopoulos; Krish Ragunath; Anthony Shonde; Christopher J Hawkey; Kenshi Yao

    2006-01-01

    Endoscopic visualisation of gastric atrophy is usually not feasible with conventional endoscopy. Magnifying endoscopy is helpful to analyze the subepithelial microvascular architecture as well as the mucosal surface microstructure without tissue biopsy. Using this technique we were able to describe the normal gastric microvasculature pattern and we also identified characteristic patterns in two cases of autoimmune atrophic gastritis.

  16. Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes

    Science.gov (United States)

    Orešič, Matej; Simell, Satu; Sysi-Aho, Marko; Näntö-Salonen, Kirsti; Seppänen-Laakso, Tuulikki; Parikka, Vilhelmiina; Katajamaa, Mikko; Hekkala, Anne; Mattila, Ismo; Keskinen, Päivi; Yetukuri, Laxman; Reinikainen, Arja; Lähde, Jyrki; Suortti, Tapani; Hakalax, Jari; Simell, Tuula; Hyöty, Heikki; Veijola, Riitta; Ilonen, Jorma; Lahesmaa, Riitta; Knip, Mikael; Simell, Olli

    2008-01-01

    The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward β cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic and permanently autoantibody negative. Individuals who developed diabetes had reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth, reduced levels of triglycerides and antioxidant ether phospholipids throughout the follow up, and increased levels of proinflammatory lysoPCs several months before seroconversion to autoantibody positivity. The lipid changes were not attributable to HLA-associated genetic risk. The appearance of insulin and glutamic acid decarboxylase autoantibodies was preceded by diminished ketoleucine and elevated glutamic acid. The metabolic profile was partially normalized after the seroconversion. Autoimmunity may thus be a relatively late response to the early metabolic disturbances. Recognition of these preautoimmune alterations may aid in studies of disease pathogenesis and may open a time window for novel type 1 diabetes prevention strategies. PMID:19075291

  17. Glucose Driven Changes in Beta Cell Identity Are Important for Function and Possibly Autoimmune Vulnerability during the Progression of Type 1 Diabetes

    Science.gov (United States)

    Weir, Gordon C.; Bonner-Weir, Susan

    2017-01-01

    This commentary explores the hypothesis that when autoimmunity leads to a fall of beta cell mass during the progression of type 1 diabetes (T1D), rising glucose levels cause major changes in beta cell identity. This then leads to profound changes in secretory function and less well-understood changes in beta cell susceptibility to autoimmune destruction, which may influence of rate of progression of beta cell killing. PMID:28174593

  18. Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2.

    Science.gov (United States)

    Hoffmanová, I; Sánchez, D; Hábová, V; Anděl, M; Tučková, L; Tlaskalová-Hogenová, H

    2015-01-01

    Impairment of mucosal barrier integrity of small intestine might be causative in immune-mediated gastrointestinal diseases. We tested the markers of epithelial apoptosis - cytokeratin 18 caspase-cleaved fragment (cCK-18), and enterocyte damage - intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14) in sera of patients with untreated celiac disease (CLD), those on gluten-free diet (CLD-GFD), patients with autoimmune diabetes mellitus (T1D), T1D with insulitis (T1D/INS), and diabetes mellitus type 2 (T2D). We found elevated levels of cCK-18 (Pdiabetes.

  19. How to assess the severity of atrophic gastritis

    Institute of Scientific and Technical Information of China (English)

    Yan-Cheng Dai; Zhi-Peng Tang; Ya-Li Zhang

    2011-01-01

    Atrophic gastritis, is the main consequence of long-standing Helicobacter pylori infection, and is linked to the development of gastric cancer. The severity of atrophic gastritis is related to the lifetime risk of gastric cancer development, especially in terms of its degree and extent of mucosal damage. Therefore, it is important for clinicians to assess the severity of atrophic gastritis, interfere with the disease progress, and reverse gastric mucosal atrophy. In the article, we demonstrated some methods (conventional endoscopy, modern endoscopic technology and noninvasive methods) that may help assess the severity of atrophic gastritis and select the reasonable treatment protocols.

  20. Absence of autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease in girls and women with Turner syndrome

    Directory of Open Access Journals (Sweden)

    Kämpe Olle

    2007-12-01

    Full Text Available Abstract Background A disturbance in the immune system has been described in Turner syndrome (45,X, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45,X, thyroiditis being the most common. Other autoimmune diseases seen are inflammatory bowel disease, insulin dependent diabetes mellitus, Addison's disease, rheumatoid arthritis, myasthenia gravis, vitiligo, alopecia, pernicious anaemia and hypoparathyroidism, but the association to Turner syndrome is not definite. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency ear problems are common. Otitis media and a progressive sensorineural hearing disorder are commonly seen. In the normal population there are known inner ear disorders related to autoimmune diseases. The aim of this study was to investigate patients with Turner syndrome regarding autoantibodies connected to the autoimmune disorders; autoimmune polyendocrine syndrome type I and II and Addison's disease, to screen for overlapping profile of autoantibodies. Blood samples from 110 Turner patients (7–65 years were investigated using in vitro transcription, translation and immunoprecipitation techniques regarding autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease (21-hydroxylase, 17α-hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase, tyrosine hydroxylase and tryptophan hydroxylase. Results The autoantibodies investigated were not overrepresented among the Turner patients. Conclusion The autoimmune disorders associated with Turner syndrome do not seem to be of the same origin as Addison's disease, the type I or II autoimmune polyendocrine syndrome.

  1. Overdenture locator attachments for atrophic mandible.

    Science.gov (United States)

    Mahajan, Neerja; Thakkur, Rahul K

    2013-10-01

    Implant-supported overdentures provide a good opportunity for dentists to improve oral health and quality-of-life of patients. Atrophic mandible poses a significant challenge to successful oral rehabilitation with dental implants. In this article, the fabrication of lower overdenture by two narrow platform implants is described with dual retentive, resilient, self-locating locator attachment system. The locator attachment system has the lowest profile in comparison with the ball and bar attachments and is versatile up to 40° of divergence between two implants. By using locators as attachments, we can meet functional, economic and social expectation of patients with ease and satisfaction.

  2. Overdenture locator attachments for atrophic mandible

    Directory of Open Access Journals (Sweden)

    Neerja Mahajan

    2013-01-01

    Full Text Available Implant-supported overdentures provide a good opportunity for dentists to improve oral health and quality-of-life of patients. Atrophic mandible poses a significant challenge to successful oral rehabilitation with dental implants. In this article, the fabrication of lower overdenture by two narrow platform implants is described with dual retentive, resilient, self-locating locator attachment system. The locator attachment system has the lowest profile in comparison with the ball and bar attachments and is versatile up to 40΀ of divergence between two implants. By using locators as attachments, we can meet functional, economic and social expectation of patients with ease and satisfaction.

  3. [Autoimmune pancreatitis].

    Science.gov (United States)

    Beyer, G; Menzel, J; Krüger, P-C; Ribback, S; Lerch, M M; Mayerle, J

    2013-11-01

    Autoimmune pancreatitis is a relatively rare form of chronic pancreatitis which is characterized by a lymphoplasmatic infiltrate with a storiform fibrosis and often goes along with painless jaundice and discrete discomfort of the upper abdomen. Clinically we distinguish between two subtypes, which differ in terms of their histology, clinical picture and prognosis. Type 1 autoimmune pancreatitis is the pancreatic manifestation of the IgG4-associated syndrome which also involves other organs. About one third of the patients can only be diagnosed after either histological prove or a successful steroid trail. Type 2 is IgG4-negative with the histological picture of an idiopathic duct centric pancreatitis and is to higher degree associated with inflammatory bowel disease. A definitive diagnosis can only be made using biopsy. Usually both forms show response to steroid treatment, but in type 1 up to 50 % of the patients might develop a relapse. The biggest challenge and most important differential diagnosis remains the discrimination of AIP from pancreatic cancer, because also AIP can cause mass of the pancreatic head, lymphadenopathy and ductal obstruction. This article summarizes recent advances on epidemiology, clinical presentation, diagnostic strategy, therapy and differential diagnosis in this relatively unknown disease.

  4. [Polyglandular autoimmune syndromes : An overview].

    Science.gov (United States)

    Komminoth, P

    2016-05-01

    Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion.

  5. Bacteroides dorei dominates gut microbiome prior to autoimmunity in Finnish children at high risk for type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Austin G Davis-Richardson

    2014-12-01

    Full Text Available The incidence of the autoimmune disease, type 1 diabetes (T1D, has increased dramatically over the last half century in many developed countries and is particularly high in Finland and other Nordic countries. Along with genetic predisposition, environmental factors are thought to play a critical role in this increase. As with other autoimmune diseases, the gut microbiome is thought to play a potential role in controlling progression to T1D in children with high genetic risk, but we know little about how the gut microbiome develops in children with high genetic risk for T1D. In this study, the early development of the gut microbiomes of 76 children at high genetic risk for T1D was determined using high-throughput 16S rRNA gene sequencing. Stool samples from children born in the same hospital in Turku, Finland were collected at monthly intervals beginning at 4-6 months after birth until 2.2 years of age. Of those 76 children, 29 seroconverted to T1D-related autoimmunity (cases including 22 who later developed T1D, the remaining 47 subjects remained healthy (controls. While several significant compositional differences in low abundant species prior to seroconversion were found, one highly abundant group composed of two closely related species, Bacteroides dorei and Bacteroides vulgatus, was significantly higher in cases compared to controls prior to seroconversion. Metagenomic sequencing of samples high in the abundance of the B. dorei/vulgatus group before seroconversion, as well as longer 16S rRNA sequencing identified this group as Bacteroides dorei. The abundance of B. dorei peaked at 7.6 months in cases, over eight months prior to the appearance of the first islet autoantibody, suggesting that early changes in the microbiome may be useful for predicting T1D autoimmunity in genetically susceptible infants. The cause of increased B. dorei abundance in cases is not known but its timing appears to coincide with the introduction of solid food.

  6. Development of autoimmune hepatitis type I after pulsed methylprednisolone therapy for multiple sclerosis: A case report

    Institute of Scientific and Technical Information of China (English)

    Atsushi Takahashi; Hirornasa Ohira; Yukiko Kanno; Yuta Takahashi; Natsumi Sakamoto; Kyoko Monoe; Hironobu Saito; Kazumichi Abe; Junko Yokokawa; Atsushi Irisawa

    2008-01-01

    A 43-year-old woman with multiple sclerosis (MS) was treated with pulsed methylprednisolone and interferon β at a hospital.Four weeks after initiating treatment,liver dysfunction occurred and she was referred and admitted to our hospital.Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis,but not for autoimmune hepatitis (AIH).She was successfully treated with corticosteroids.As ataxia developed after 1 year,she was treated with pulsed methylprednisolone for 3 days,then readmitted to our hospital when liver dysfunction occurred.Clinical and laboratory findings led to the diagnosis of A[H.To the best of our knowledge,this is the second case of AIH developed after pulsed methylprednisolone for MS.

  7. Type of fish consumed and thyroid autoimmunity in pregnancy and postpartum.

    Science.gov (United States)

    Benvenga, Salvatore; Vigo, Maria Teresa; Metro, Daniela; Granese, Roberta; Vita, Roberto; Le Donne, Maria

    2016-04-01

    Fish consumption or supplementation with omega-3 fatty acids was reported to cure and/or prevent autoimmune and nonautoimmune disorders. Serum positivity for thyroid autoantibodies is a predictive marker of postpartum thyroiditis and postpartum depression. We hypothesized that stable consumption of the omega-3-rich oily fish was associated with a more favorable profile of serum thyroid antibodies throughout pregnancy and early postpartum compared with stable consumption of swordfish, a predator that concentrates pollutants. We prospectively measured serum thyroglobulin antibodies and thyroperoxidase antibodies in pregnancy (first, second trimesters) and postpartum (day 4), in 236 thyroid disease-free, nonsmoker Caucasian women with stable dietary habits. We did not measure thyroid autoantibodies prior to pregnancy. Women were divided into groups A (n = 48; swordfish), B (n = 52; oily fish), C (n = 68; swordfish + other fish, not necessarily oily fish), and D (n = 68; fish other than swordfish and oily fish). Major endpoints were positivity rates and serum concentrations of the two autoantibodies. We resorted to previous studies for the estimated content of fatty acids and microelements in the consumed fish. Positivity rates and serum concentrations of both antibodies were the greatest in group A and the lowest in group B (P fish consumption and serum concentrations of either antibody was direct in group A but inverse in group B. The estimated content of omega-3 fatty acids in fish consumed by group B was the greatest (P fish as a favorable alternative. Because thyroid autoantibodies are markers of autoimmune-related postpartum problems, our data suggest a dietary prophylaxis of such problems.

  8. Autoimmune hepatitis

    Directory of Open Access Journals (Sweden)

    F Motamed

    2014-04-01

    Full Text Available Autoimmune hepatitis is (AIH is a chronic hepatitis that occurs in children and adults of all ages. It is characterized by immunologic and autoimmune features, including circulating auto antibodies and high serum globulin concentrations. It was first described in the 1950s by term of chronic active hepatitis. It has 2 types with different auto antibodies. Diagnosis is based upon serologic and histologic findings and exclusion of other forms of chronic liver disease.   A scoring system should be used in assessment based upon: 1 Auto anti bodie titer 2 Serum IgG level  3 Liver histology 4 Absence of viral and other causes of hepatitis. Clear indications for treatment: 1   rise of aminotrasferases 2   clinical symptoms of liver disease 3   histological features in liver biopsy 4   Children with AIH initial treatment involve glucocorticoid with or without azathioprine. For patients with fulminant hepatitis liver transplantation, should be kept in mind.   Remission is defined by: 1   Resolution of symptoms 2   Normalization of serum trasaminases 3   Normalization of serum bilirubin and gamma globuline levels. 4   Improvement in liver histology 5   Treatment is continued for at least 2-5 years, glucocorticoids are with drawn first, by tapering over six weeks. Azathioprine will be with drawn.  

  9. A unique combination of autoimmune limbic encephalitis, type 1 diabetes, and Stiff person syndrome associated with GAD-65 antibody.

    Science.gov (United States)

    Sharma, Chandra Mohan; Pandey, Rajendra Kumar; Kumawat, Banshi Lal; Khandelwal, Dinesh; Gandhi, Pankaj

    2016-01-01

    Antibodies to GAD-65 have been implicated in the pathogenesis of type 1 diabetes, limbic encephalitis and Stiff person syndrome, however these diseases rarely occur concurrently. We intend to present a rare case of 35 year old female who was recently diagnosed as having type 1 diabetes presented with 1½ month history of recurrent seizures, subacute onset gait ataxia, dysathria, psychiatric disturbance and cognitive decline. No tumor was found on imaging and the classic paraneoplastic panel was negative. Cerebrospinal fluid and blood was positive for GAD-65 antibodies. Patient showed significant improvement with immunomodulatory therapy. Association of GAD-65 antibodies has been found with various disorders including type 1 diabetes, limbic encephalitis, Stiff person syndrome, cerebellar ataxia and palatal myoclonus. This case presents with unique combination of type 1 diabetes, Stiff person syndrome and limbic encephalitis associated with GAD-65 antibodies that is responsive to immunotherapy. It also highlights the emerging concept of autoimmunity in the causation of various disorders and there associations.

  10. Autoimmune autonomic disorders.

    Science.gov (United States)

    Mckeon, Andrew; Benarroch, Eduardo E

    2016-01-01

    Autoimmune autonomic disorders occur because of an immune response directed against sympathetic, parasympathetic, and enteric ganglia, autonomic nerves, or central autonomic pathways. In general, peripheral autoimmune disorders manifest with either generalized or restricted autonomic failure, whereas central autoimmune disorders manifest primarily with autonomic hyperactivity. Some autonomic disorders are generalized, and others are limited in their anatomic extent, e.g., isolated gastrointestinal dysmotility. Historically, these disorders were poorly recognized, and thought to be neurodegenerative. Over the last 20 years a number of autoantibody biomarkers have been discovered that have enabled the identification of certain patients as having an autoimmune basis for either autonomic failure or hyperactivity. Peripheral autoimmune autonomic disorders include autoimmune autonomic ganglionopathy (AAG), paraneoplastic autonomic neuropathy, and acute autonomic and sensory neuropathy. AAG manifests with acute or subacute onset of generalized or selective autonomic failure. Antibody targeting the α3 subunit of the ganglionic-type nicotinic acetylcholine receptor (α3gAChR) is detected in approximately 50% of cases of AAG. Some other disorders are characterized immunologically by paraneoplastic antibodies with a high positive predictive value for cancer, such as antineuronal nuclear antibody, type 1 (ANNA-1: anti-Hu); others still are seronegative. Recognition of an autoimmune basis for autonomic disorders is important, as their manifestations are disabling, may reflect an underlying neoplasm, and have the potential to improve with a combination of symptomatic and immune therapies.

  11. Imaging dynamics of CD11c+ cells and Foxp3+ cells in progressive autoimmune insulitis in the NOD mouse model of type 1 diabetes

    DEFF Research Database (Denmark)

    Schmidt-Christensen, Anja; Hansen, Lisbeth; Ilegems, Erwin

    2013-01-01

    Aims/hypothesis The aim of this study was to visualise the dynamics and interactions of the cells involved in autoimmune-driven inflammation in type 1 diabetes. Methods We adopted the anterior chamber of the eye (ACE) transplantation model to perform non-invasive imaging of leucocytes infiltratin...

  12. Autoimmune polyglandular syndrome type 2 manifested as Hashimoto's thyroiditis and adrenocortical insufficiency, in Turner syndrome woman, with onset following introduction of treatment with recombinant human growth hormone.

    Science.gov (United States)

    Cyniak-Magierska, Anna; Lasoń, Agnieszka; Smyczyńska, Joanna; Lewiński, Andrzej

    2015-01-01

    Autoimmune polyglandular syndrome is a constellation of signs and symptoms of simultaneous insufficiencies of several endocrine glands. Autoimmune polyglandular syndrome type 2 (APS 2) may be diagnosed when the adrenocortical insufficiency is associated with an autoimmune thyroid disease (Hashimoto's thyroiditis or Graves' disease), and/or insulin-dependent diabetes mellitus. Turner syndrome is the most common chromosomal disorder in females, caused by complete or partial X chromosome monosomy. We present the case of a 20-year-old woman with Turner syndrome, in whom APS 2 (Hashimoto's thyroiditis and adrenocortical insufficiency) has been diagnosed after introduction of recombinant human growth hormone (rhGH) therapy. In Turner syndrome, examination of the patient must regularly be conducted in order to diagnose a possible onset of autoimmune diseases; respective treatment must be applied as soon as the diagnosis is established. In particular, therapy of rhGH, used for short stature treatment, may be a trigger factor of adrenal insufficiency. The cortisol level in blood should be assessed before rhGH administration and carefully monitored during the therapy, especially in case of autoimmune thyroid disease coexistence.

  13. Autoimmune epilepsy.

    Science.gov (United States)

    Greco, Antonio; Rizzo, Maria Ida; De Virgilio, Armando; Conte, Michela; Gallo, Andrea; Attanasio, Giuseppe; Ruoppolo, Giovanni; de Vincentiis, Marco

    2016-03-01

    Despite the fact that epilepsy is the third most common chronic brain disorder, relatively little is known about the processes leading to the generation of seizures. Accumulating data support an autoimmune basis in patients with antiepileptic drug-resistant seizures. Besides, recent studies show that epilepsy and autoimmune disease frequently co-occur. Autoimmune epilepsy is increasingly recognized in the spectrum of neurological disorders characterized by detection of neural autoantibodies in serum or spinal fluid and responsiveness to immunotherapy. An autoimmune cause is suspected based on frequent or medically intractable seizures and the presence of at least one neural antibody, inflammatory changes indicated in serum or spinal fluid or on MRI, or a personal or family history of autoimmunity. It is essential that an autoimmune etiology be considered in the initial differential diagnosis of new onset epilepsy, because early immunotherapy assures an optimal outcome for the patient.

  14. Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Pipi, Elena; Marketou, Marietta; Tsirogianni, Alexandra

    2014-08-15

    Ever since its first appearance among the multiple forms of diabetes, latent autoimmune diabetes in adults (LADA), has been the focus of endless discussions concerning mainly its existence as a special type of diabetes. In this mini-review, through browsing important peer-reviewed publications, (original articles and reviews), we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity. A unique combination of immunological, clinical and metabolic characteristics has been identified in this group of patients, namely persistent islet cell antibodies, high frequency of thyroid and gastric autoimmunity, DR3 and DR4 human leukocyte antigen haplotypes, progressive loss of beta cells, adult disease onset, normal weight, defective glycaemic control, and without tendency to ketoacidosis. Although anthropomorphic measurements are useful as a first line screening, the detection of C-peptide levels and the presence of glutamic acid decarboxylase (GAD) autoantibodies is undoubtedly the sine qua non condition for a confirmatory LADA diagnosis. In point of fact, GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied. Nevertheless, the lack of diagnostic criteria and guidelines still puzzle the physicians, who struggle between early diagnosis and correct timing for insulin treatment.

  15. Immunosuppressive drugs for the treatment of autoimmune pancreatitis.

    Science.gov (United States)

    Pezzilli, Raffaele

    2014-01-01

    Autoimmune pancreatitis is one of the few diseases of the pancreas characterized by the possibility of curing the illness using immunosuppressant drugs. In this paper, the therapeutic approach used to treat autoimmune pancreatitis patients and the clinical outcome related to each treatment modality were reviewed. Steroids are useful in alleviating the symptoms of the acute presentation of autoimmune pancreatitis, but some questions remain open, such as a shared definition of the disease's remission as well as autoimmune pancreatitis relapse, the dosage of steroids in the symptomatic phase of the disease and the duration of steroid therapy. Finally, it should be determined if other immunosuppressive nonsteroidal drugs could become first-line therapy in patients with autoimmune pancreatitis without jaundice and without atrophic pancreas.

  16. Immunometabolism and autoimmunity.

    Science.gov (United States)

    Freitag, Jenny; Berod, Luciana; Kamradt, Thomas; Sparwasser, Tim

    2016-11-01

    A continuous increase in the prevalence of autoimmune diseases is to be expected in the aging societies worldwide. Autoimmune disorders not only cause severe disability and chronic pain, but also lead to considerable socio-economic costs. Given that the current treatment options are not curative, have substantial side effects and a high percentage of non-responders, innovative options to the existing therapeutic armament against autoimmune diseases are urgently required. Accumulating evidence suggests that changes in the metabolism of immune cells are associated with, and contribute to the pathogenesis of autoimmunity. Additionally, some autoimmune diseases share alterations in metabolic pathways, key metabolites or metabolic byproducts such as reactive oxygen species. Other examples for metabolic changes in autoimmune settings include modifications in amino acid and cholesterol levels or glucose catabolism. Thus, the emerging field of immunometabolism may hold the potential to discover new therapeutic targets. Here, we discuss recent findings describing metabolic changes in autoimmune arthritis, multiple sclerosis as well as type 1 diabetes, focusing on pathophysiological aspects.

  17. LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders.

    Science.gov (United States)

    Soós, Zsuzsanna; Salamon, Mónika; Erdei, Katalin; Kaszás, Nóra; Folyovich, András; Szücs, Anna; Barcs, Gábor; Arányi, Zsuzsanna; Skaliczkis, József; Vadasdi, Károly; Winkler, Gábor

    2014-05-30

    Celiac disease--in its typical form--is a chronic immune-mediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment.

  18. Treated Autoimmune Thyroid Disease Is Associated with a Decreased Quality of Life among Young Persons with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Alena Spirkova

    2015-01-01

    Full Text Available Type 1 diabetes (T1D in children and adolescents is relatively often accompanied by other immunopathological diseases, autoimmune thyroid disease (AITD or celiac disease (CD. Our aim was to assess whether these conditions are associated with changes in the health-related quality of life (HRQOL in pediatric patients with T1D. In a cross-sectional study we identified eligible 332 patients with T1D aged 8–18 years, of whom 248 (75% together with their parents responded to the PedsQL Generic and Diabetes Modules. Compared to 143 patients without thyroid autoantibodies, 40 patients with a thyroxine-treated AITD scored lower in the overall generic HRQOL (P=0.014, as well as in the overall diabetes-specific HRQOL (P=0.013. After adjustment for age, gender, duration of diabetes, type of diabetes treatment, and diabetes control, this association remained statistically significant for the generic HRQOL (P=0.023. Celiac disease was not associated with a change in the generic or diabetes-specific HRQOL (P=0.07  and   P=0.63, resp.. Parental scores showed no association with AITD or celiac disease, except a marginally significant decrease in the overall generic HRQOL (P=0.039 in the T1D + AITD compared to T1D group. Our study indicates that, in pediatric patients with T1D, concomitant thyroxine-treated AITD is associated with lower quality of life.

  19. Linking chronic infection and autoimmune diseases: Mycobacterium avium subspecies paratuberculosis, SLC11A1 polymorphisms and type-1 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Daniela Paccagnini

    Full Text Available BACKGROUND: The etiology of type 1 diabetes mellitus (T1DM is still unknown; numerous studies are performed to unravel the environmental factors involved in triggering the disease. SLC11A1 is a membrane transporter that is expressed in late endosomes of antigen presenting cells involved in the immunopathogenic events leading to T1DM. Mycobacterium avium subsp. paratuberculosis (MAP has been reported to be a possible trigger in the development of T1DM. METHODOLOGY/PRINCIPAL FINDINGS: Fifty nine T1DM patients and 79 healthy controls were genotyped for 9 polymorphisms of SLC11A1 gene, and screened for the presence of MAP by PCR. Differences in genotype frequency were evaluated for both T1DM patients and controls. We found a polymorphism in the SLC11A1 gene (274C/T associated to type 1 diabetic patients and not to controls. The presence of MAP DNA was also significantly associated with T1DM patients and not with controls. CONCLUSIONS/SIGNIFICANCE: The 274C/T SCL11A1 polymorphism was found to be associated with T1DM as well as the presence of MAP DNA in blood. Since MAP persists within macrophages and it is also processed by dendritic cells, further studies are necessary to evaluate if mutant forms of SLC11A1 alter the processing or presentation of MAP antigens triggering thereby an autoimmune response in T1DM patients.

  20. The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors.

    Science.gov (United States)

    Tüzün, Ali; Keskin, Onur; Yakut, Mustafa; Kalkan, Cagdas; Soykan, Irfan

    2014-01-01

    Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.

  1. Spontaneous healing of an atrophic pseudoarthrosis during femoral lengthening : A case report with six-year follow-up

    OpenAIRE

    1999-01-01

     A seven-year old girl developed an atrophic pseudoarthrosis at the midshaft of the femur with 8.5 cm of femoral shortening after an open type II fracture. During a femoral lengthening procedure, the pseudoarthrosis filled with spontaneous callus formation and bone union was obtained.

  2. Autoimmune myelopathies.

    Science.gov (United States)

    Flanagan, Eoin P

    2016-01-01

    Autoimmune myelopathies are a heterogeneous group of immune-mediated spinal cord disorders with a broad differential diagnosis. They encompass myelopathies with an immune attack on the spinal cord (e.g., aquaporin-4-IgG (AQP4-IgG) seropositive neuromyelitis optica (NMO) and its spectrum disorders (NMOSD)), myelopathies occurring with systemic autoimmune disorders (which may also be due to coexisting NMO/NMOSD), paraneoplastic autoimmune myelopathies, postinfectious autoimmune myelopathies (e.g., acute disseminated encephalomyelitis), and myelopathies thought to be immune-related (e.g., multiple sclerosis and spinal cord sarcoidosis). Spine magnetic resonance imaging is extremely useful in the evaluation of autoimmune myelopathies as the location of signal change, length of the lesion, gadolinium enhancement pattern, and evolution over time narrow the differential diagnosis considerably. The recent discovery of multiple novel neural-specific autoantibodies accompanying autoimmune myelopathies has improved their classification. These autoantibodies may be pathogenic (e.g., AQP4-IgG) or nonpathogenic and more reflective of a cytotoxic T-cell-mediated autoimmune response (collapsin response mediator protein-5(CRMP5)-IgG). The presence of an autoantibody may help guide cancer search, assist treatment decisions, and predict outcome/relapse. With paraneoplastic myelopathies the initial goal is detection and treatment of the underlying cancer. The aim of immunotherapy in all autoimmune myelopathies is to maximize reversibility, maintain benefits (while preventing relapse), and minimize side effects.

  3. Association of tumor necrosis factor genetic polymorphism with chronic atrophic gastritis and gastric adenocarcinoma in Chinese Han population

    Institute of Scientific and Technical Information of China (English)

    Bao-Ying Fei; Bing Xia; Chang-Sheng Deng; Xiao-Qing Xia; Min Xie; J Bart A Crusius; A Salvador Pena

    2004-01-01

    AIM: To investigate the association of TNF polymorphisms with chronic atrophic gastritis (CAG) and gastric adenocarcinoma in Chinese Han patients.METHODS: The TNFa-e 5 microsatellites and 3 RFLP sites were typed using PCR technique, followed by high-voltage denaturing PAGE with silver staining and restriction enzyme digestion respectively in specimens from 53 patients with CAG and 56 patients with gastric adenocarcinoma and 164 healthy controls. The PCR products were cloned and sequenced.RESULTS: The frequency of TNF-β Ncol*1/2 genotype was higher in patients with chronic atrophic gastritis than in healthy controls, but no significant difference was observed (60.38% vs 46.34%, P=0.076). The frequency of TNa10 allele was significantly higher in patients with chronic atrophic gastritis than in healthy controls (19.81% vs 11.89%,P=0.04). However, it did not relate to age, gender, atrophic degree or intestinal metaplasia in patients with chronic atrophic gastritis. The frequency of TNF-β Ncol*1/2 and d2/d6 genotypes were significantly higher in patients with gastric adenocarcinoma than in healthy individuals(P>0.05).However, TNF-β Ncol*1/2 and d2/d6 genotypes did not relate to age, gender, grade of differentiation and clinicopathologic stage in patients with gastric adenocarcinoma. The frequency of TNFa6b5c1 haplotype homozygote was significantly lower in patients with gastric adenocarcinoma than in healthy controls (1.79% vs15.85%, P=0.006).CONCLUSION: TNFa10 allele may be a risk factor for chronic atrophic gastritis. TNF-β Ncol*1/2 and d2/d6 genotypes are associated with the susceptibility to gastric adenocarcinoma,whereas TNFa6b5c1 haplotype homozygote may contribute to the resistance against gastric adenocarcinoma.

  4. Autoantibodies in autoimmune liver diseases.

    Science.gov (United States)

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  5. Lack of association of type 2 diabetes susceptibility genotypes and body weight on the development of islet autoimmunity and type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Christiane Winkler

    Full Text Available AIM: To investigate whether type 2 diabetes susceptibility genes and body weight influence the development of islet autoantibodies and the rate of progression to type 1 diabetes. METHODS: Genotyping for single nucleotide polymorphisms (SNP of the type 2 diabetes susceptibility genes CDKAL1, CDKN2A/2B, FTO, HHEX-IDE, HMGA2, IGF2BP2, KCNJ11, KCNQ1, MTNR1B, PPARG, SLC30A8 and TCF7L2 was obtained in 1350 children from parents with type 1 diabetes participating in the BABYDIAB study. Children were prospectively followed from birth for islet autoantibodies and type 1 diabetes. Data on weight and height were obtained at 9 months, 2, 5, 8, 11, and 14 years of age. RESULTS: None of type 2 diabetes risk alleles at the CDKAL1, CDKN2A/2B, FTO, HHEX-IDE, HMGA2, IGF2BP2, KCNJ11, KCNQ1, MTNR1B, PPARG and SLC30A8 loci were associated with the development of islet autoantibodies or diabetes. The type 2 diabetes susceptible genotype of TCF7L2 was associated with a lower risk of islet autoantibodies (7% vs. 12% by age of 10 years, P = 0.015, P(corrected = 0.18. Overweight children at seroconversion did not progress to diabetes faster than non-overweight children (HR: 1.08; 95% CI: 0.48-2.45, P>0.05. CONCLUSIONS: These findings do not support an association of type 2 diabetes risk factors with islet autoimmunity or acceleration of diabetes in children with a family history of type 1 diabetes.

  6. Autoimmunity in visual loss.

    Science.gov (United States)

    Petzold, Axel; Wong, Sui; Plant, Gordon T

    2016-01-01

    Neuroretinitis) are of obscure pathogenesis but an autoimmune disorder of the post-infectious type is plausible. Visual loss in autoimmunity is an expanding field: the most significant advances in research have resulted from taking a well characterised phenotype and making educated guesses at the possible molecular targets of autoimmune attack.

  7. Circulating Ribonucleic Acids and Metabolic Stress Parameters May Reflect Progression of Autoimmune or Inflammatory Conditions in Juvenile Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Gordana Kocic

    2011-01-01

    Full Text Available The sensing of ribonucleic acids (RNAs by the monocyte/macrophage system occurs through the TLR7/8 Toll-like receptor family, the retinoic acidi–nducible protein I (RIG-I, and the melanoma differentiation–associated protein-5 (MDA-5. The aim of the present study was to evaluate the effect of circulating RNAs, isolated from juvenile type 1 diabetic patients and healthy control children, on the inflammatory, apoptotic, and antiviral response in human peripheral blood mononuclear cells (PBMCs isolated from a healthy donor. Obtained effects were compared to the effects of metabolic stress parameters (hyperglycemia, oxidative and nitrosative stress. Forty-eight patients with juvenile type 1 diabetes and control children were included in the study. By performing the chromatographic analysis of circulating RNAs, the peak at the retention time 0.645 min for diabetic and control RNA samples was identified. To determine whether circulating RNAs have an agonistic or antagonistic effect on the signaling pathways involved in inflammatory, apoptotic, and antiviral cascade, their effect on TLR8, RIG-I, MDA-5, MyD88, NF-κB, IRF-3, phosphoIRF-3, IRF-7, RIP, and p38 was evaluated. A significantly lower level was achieved by cultivating PBMCs with circulating RNAs isolated from type 1 diabetic children, compared to the intact PBMCs, in relation to TLR-8, MDA-5, NF-κB, phospho IRF-3, and RIP, while it was higher for Bax. All the metabolic stress conditions up-regulated NF-κB, Bcl-2, and Bax. The NF-κB, determination seems to be the most sensitive parameter that may reflect disease processes associated with the progression of autoimmune or inflammatory conditions, while the IRF3/phosphoIRF3 ratio may suggest an insufficient antiviral response.

  8. Circulating ribonucleic acids and metabolic stress parameters may reflect progression of autoimmune or inflammatory conditions in juvenile type 1 diabetes.

    Science.gov (United States)

    Kocic, Gordana; Pavlovic, Radmila; Najman, Stevo; Nikolic, Goran; Sokolovic, Dusan; Jevtovic-Stoimenov, Tatjana; Musovic, Dijana; Veljkovic, Andrej; Kocic, Radivoj; Djindjic, Natasa

    2011-07-28

    The sensing of ribonucleic acids (RNAs) by the monocyte/macrophage system occurs through the TLR7/8 Toll-like receptor family, the retinoic acid-inducible protein I (RIG-I), and the melanoma differentiation-associated protein-5 (MDA-5). The aim of the present study was to evaluate the effect of circulating RNAs, isolated from juvenile type 1 diabetic patients and healthy control children, on the inflammatory, apoptotic, and antiviral response in human peripheral blood mononuclear cells (PBMCs) isolated from a healthy donor. Obtained effects were compared to the effects of metabolic stress parameters (hyperglycemia, oxidative and nitrosative stress). Forty-eight patients with juvenile type 1 diabetes and control children were included in the study. By performing the chromatographic analysis of circulating RNAs, the peak at the retention time 0.645 min for diabetic and control RNA samples was identified. To determine whether circulating RNAs have an agonistic or antagonistic effect on the signaling pathways involved in inflammatory, apoptotic, and antiviral cascade, their effect on TLR8, RIG-I, MDA-5, MyD88, NF-KB, IRF-3, phosphoIRF-3, IRF-7, RIP, and p38 was evaluated. A significantly lower level was achieved by cultivating PBMCs with circulating RNAs isolated from type 1 diabetic children, compared to the intact PBMCs, in relation to TLR-8, MDA-5, NF-KB, phospho IRF-3, and RIP, while it was higher for Bax. All the metabolic stress conditions up-regulated NF-KB, Bcl-2, and Bax. The NF-êB determination seems to be the most sensitive parameter that may reflect disease processes associated with the progression of autoimmune or inflammatory conditions, while the IRF3/phosphoIRF3 ratio may suggest an insufficient antiviral response.

  9. Differentiation of focal-type autoimmune pancreatitis from pancreatic carcinoma: assessment by multiphase contrast-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    Furuhashi, Naohiro; Suzuki, Kojiro; Sakurai, Yusuke; Naganawa, Shinji [Nagoya University Graduate School of Medicine, Department of Radiology, Nagoya (Japan); Ikeda, Mitsuru [Nagoya University Graduate School of Medicine, Department of Radiological Technology, Nagoya (Japan); Kawai, Yuichi [Japanese Red Cross Nagoya Daiichi Hospital, Department of Diagnostic Radiology, Nagoya (Japan)

    2015-05-01

    To evaluate the utility of multiphase contrast-enhanced computed tomography (CT) findings alone and in combination for differentiating focal-type autoimmune pancreatitis (f-AIP) from pancreatic carcinoma (PC). The study group comprised 22 f-AIP lesions and 61 PC lesions. Two radiologists independently evaluated CT findings. Frequencies of findings were compared between f-AIP and PC. Statistical, univariate and multivariate analyses were performed. Homogeneous enhancement during the portal phase (AIP, 59 % vs. PC, 3 %; P < 0.001), dotted enhancement during the pancreatic phase (50 % vs. 7 %; P < 0.001), duct-penetrating sign (46 % vs. 2 %; P < 0.001), enhanced duct sign (36 % vs. 2 %; P < 0.001) and capsule-like rim (46 % vs. 3 %; P < 0.001) were more frequently observed in AIP. Ring-like enhancement during the delayed phase (5 % vs. 46 %; P < 0.001) and peripancreatic strands with a length of at least 10 mm (5 % vs. 39 %; P = 0.001) were more frequently observed in PC. AIP was identified with 82 % sensitivity and 98 % specificity using four of these seven findings. Multivariate analysis revealed significant differences in dotted enhancement (P = 0.004), duct-penetrating sign (P < 0.001) and capsule-like rim (P = 0.007). The combination of CT findings may allow improvements in differentiating f-AIP from PC. (orig.)

  10. TRAF6 is essential for maintenance of regulatory T cells that suppress Th2 type autoimmunity.

    Directory of Open Access Journals (Sweden)

    Go Muto

    Full Text Available Regulatory T cells (Tregs maintain immune homeostasis by limiting inflammatory responses. TRAF6 plays a key role in the regulation of innate and adaptive immunity by mediating signals from various receptors including the T-cell receptor (TCR. T cell-specific deletion of TRAF6 has been shown to induce multiorgan inflammatory disease, but the role of TRAF6 in Tregs remains to be investigated. Here, we generated Treg-specific TRAF6-deficient mice using Foxp3-Cre and TRAF6-flox mice. Treg-specific TRAF6-deficient (cKO mice developed allergic skin diseases, arthritis, lymphadenopathy and hyper IgE phenotypes. Although TRAF6-deficient Tregs possess similar in vitro suppression activity compared to wild-type Tregs, TRAF6-deficient Tregs did not suppress colitis in lymphopenic mice very efficiently due to reduced number of Foxp3-positive cells. In addition, the fraction of TRAF6-deficient Tregs was reduced compared with wild-type Tregs in female cKO mice without inflammation. Moreover, adoptive transfer of Foxp3 (+ Tregs into Rag2(-/- mice revealed that TRAF6-deficient Tregs converted into Foxp3(- cells more rapidly than WT Tregs under lymphopenic conditions. Fate-mapping analysis also revealed that conversion of Tregs from Foxp3(+ to Foxp3(- (exFoxp3 cells was accelerated in TRAF6-deficient Tregs. These data indicate that TRAF6 in Tregs plays important roles in the maintenance of Foxp3 in Tregs and in the suppression of pathogenic Th2 type conversion of Tregs.

  11. Microangiopathic complications in type 1 diabetes mellitus: differences in severity when isolated or associated with autoimmune polyendocrinopathies

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    Patrícia Teófilo Monteagudo

    Full Text Available CONTEXT: The development and evolution of different chronic diabetic complications may present variations among the different types and conditions of this disease. OBJECTIVE: To evaluate the degree of microangiopathy in Type 1 diabetes mellitus (DM1 associated with autoimmune polyendocrinopathies (OSAD or isolated DM1 (iDM1. PATIENTS: OSAD (n=17 and iDM1 (n=13 were over 15 years old at diagnosis of DM and were matched for diabetes duration (13.9 ± 8.2 and 13.2 ± 5.9 years, respectively and metabolic control (HbA1c: 6.4 ± 1.9 and 6.8 ± 1.4%. MAIN OUTCOME MEASURES: Urinary albumin excretion (UAE; ELISA, the inversion of serum creatinine (1/C level and indirect ophthalmoscopy. RESULTS: Although the prevalence of hypertension was similar in both groups, the OSAD had inferior levels of UAE (7.4 ± 2.5 vs. 17.3 ± 9.2 µg/min; p< 0.05. Nephropathy was detected in 12% of the OSAD (none of them macroproteinuric and in 39% of the iDM1 . The UAE in the iDM1 correlated negatively with 1/C values (r= -0.7, p< 0.005, but the same did not occur in the OSAD (r= 0.2, ns. Among patients with retinopathy, the severe form was found in 29% of the OSAD and in 46% of the iDM1. CONCLUSIONS: OSAD was associated with a lower degree of microangiopathy, in spite of age at diagnosis, duration of diabetes and the metabolic control. In contrast with the iDM1 , the increase in UAE of OSAD was not associated with reductions in GFR.

  12. Atrophic Vaginitis in Breast Cancer Survivors: A Difficult Survivorship Issue

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    Joanne Lester

    2015-03-01

    Full Text Available Management of breast cancer includes systematic therapies including chemotherapy and endocrine therapy can lead to a variety of symptoms that can impair the quality of life of many breast cancer survivors. Atrophic vaginitis, caused by decreased levels of circulating estrogen to urinary and vaginal receptors, is commonly experienced by this group. Chemotherapy induced ovarian failure and endocrine therapies including aromatase inhibitors and selective estrogen receptor modulators can trigger the onset of atrophic vaginitis or exacerbate existing symptoms. Symptoms of atrophic vaginitis include vaginal dryness, dyspareunia, and irritation of genital skin, pruritus, burning, vaginal discharge, and soreness. The diagnosis of atrophic vaginitis is confirmed through patient-reported symptoms and gynecological examination of external structures, introitus, and vaginal mucosa. Lifestyle modifications can be helpful but are usually insufficient to significantly improve symptoms. Non-hormonal vaginal therapies may provide additional relief by increasing vaginal moisture and fluid. Systemic estrogen therapy is contraindicated in breast cancer survivors. Continued investigations of various treatments for atrophic vaginitis are necessary. Local estrogen-based therapies, DHEA, testosterone, and pH-balanced gels continue to be evaluated in ongoing studies. Definitive results are needed pertaining to the safety of topical estrogens in breast cancer survivors.

  13. Autoimmune disorders

    Science.gov (United States)

    ... as azathioprine, cyclophosphamide, mycophenolate, sirolimus, or tacrolimus. Targeted drugs called tumor necrosis factor (TFN) blockers can be used for some diseases. Outlook (Prognosis) The outcome depends on the disease. Most autoimmune diseases are chronic , but many can be controlled ...

  14. Autoimmune hepatitis.

    Science.gov (United States)

    Heneghan, Michael A; Yeoman, Andrew D; Verma, Sumita; Smith, Alastair D; Longhi, Maria Serena

    2013-10-26

    Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.

  15. Autoimmune hypophysitis.

    Science.gov (United States)

    Ezzat, S; Josse, R G

    1997-03-01

    Autoimmune (lymphocytic) hypophysitis has emerged as a distinct and specific clinical and pathological disease entity. Although relatively rare compared with other autoimmune endocrine diseases, nearly a hundred cases have been described. The condition is much more common in females (9:1) and appears to have a particular predilection for the pregnant and postpartum states. The anterior pituitary, and less often the neurohypophysis, appear to be the target for inflammatory autoimmune destruction. During the evolution of the disease process, pituitary hyperfunction (usually hyperprolactinemia) has been noted. This disease should now be included in the differential diagnosis of pituitary disorders, especially in females presenting with pituitary enlargement, particularly if symptoms occur in temporal relationship to pregnancy. The disease may form part of the spectrum of the polyglandular autoimmune endocrine disorders. (Trends Endocrinol Metab 1997;8:74-80). (c) 1997, Elsevier Science Inc.

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

    Directory of Open Access Journals (Sweden)

    Sadia Masood

    2014-03-01

    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.

  17. Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

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    Joselyn Rojas

    2014-01-01

    Full Text Available Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM. Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS, further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.

  18. Hepatocellular carcinoma with chronic B-type hepatitis complicated by autoimmune hemolytic anemia: A case report

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A 57-year-old man consulted a local hospital because of a persistent slight fever. At the age of 37 years he was diagnosed having B-type hepatitis, but left the liver dysfunction untreated. Twenty years later, he was diagnosed having chronic hepatitis B, hepatocellular carcinoma (HCC) and macrocytic anemia, and referred to our hospital for further investigation. A HCC with a maximum diameter of 5.2 cm was detected in segment 8. Results of blood tests included 1.8 mg/dL serum total bilirubin, 0.9 mg/dL bilirubin, less than 10 mg/dL haptoglobin, 7.9 g/dL hemoglobin, 130 fL MCV, and 14.5% reticulocytes. A bone marrow sample showed erythroid hyperplasia. The direct Coombs test gave a positive result. We diagnosed the anemia as autoimmmune hemolytic anemia (AIHA), for which prednisolone could not be administered due to positivity for HBsAg and HBeAg. After preparation of washed blood cells for later transfusion, the patient underwent systematic resection of segment 8. The cut surface of the resected specimen demonstrated an encapsulated yellow-brownish tumor measuring 52 mm × 40 mmwhich was diagnosed pathologicaly as moderately differentiated HCC. On the 9th postoperative day, the patient's temperature rose to 38℃, and exacerbated hemolysis was observed. The maximum total bilirubin value was 5.8 mg/dL and minimum hemoglobin level was 4.6 g/dL. He tolerated this period without blood transfusion. Currently he is being followed up as an outpatient, and shows no signs of HCC recurrence or symptoms of anemia. AIHA associated with HBV infection has been described in only three previous cases, and the present case is the first in which surgery was performed for accompanying HCC.

  19. Investigation of susceptibility genes triggering lachrymal/salivary gland lesion complications in Japanese patients with type 1 autoimmune pancreatitis.

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    Takaya Oguchi

    Full Text Available Autoimmune pancreatitis (AIP is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. In particular, lachrymal/salivary gland lesions tend to manifest in a highly active AIP disease state, and several genes are speculated to be associated with the onset of this complication. We therefore searched for candidate susceptibility genes related to lachrymal/salivary gland lesions in a genome-wide association study (GWAS with the GeneChip Human Mapping 500k Array Set (Affymetrix, CA that was followed by fine mapping of additional single nucleotide polymorphisms (SNPs in strongly significant genes with TaqMan assays. Venous blood samples were obtained from 50 type 1 AIP patients with lachrymal/salivary gland lesions (A group and 53 type 1 AIP patients without (B group. The mean values of IgG and IG4 were both significantly different (P<0.05 between the groups. SNPs that showed a significant association with the A group at the genome-wide level (P<0.0001 were identified and subsequently used in fine SNP mapping of candidate genes. In total, five SNPs had a positive association with complicated AIP (most notably rs2284932 [P=0.0000021] and five SNPs possessed a negative association (particularly rs9371942 [P=0.00000039]. Among them, KLF7, FRMD4B, LOC101928923, and MPPED2 were further examined for complication susceptibility using additional SNPs that were not included in the GWAS. Individual genotyping of KLF7 rs2284932 revealed that the frequency of the minor C allele was significantly increased (P = 0.00062, Pc = 0.003, OR = 2.98, 95%CI = 1.58–5.65 in group A. The minor T allele of rs4473559 in FRMD4 demonstrated a significant association in the A group (P = 0.00015, OR = 3.38, 95%CI = 1.77–6.45. In the LOC101928923 gene, the frequency of the minor T allele of rs4379306 was significantly decreased in group A in both TaqMan and GWAS analyses. Lastly, the minor C

  20. Serological evaluation of possible exposure to Ljungan virus and related parechovirus in autoimmune (type 1) diabetes in children.

    Science.gov (United States)

    Nilsson, A-L; Vaziri-Sani, F; Broberg, P; Elfaitouri, A; Pipkorn, R; Blomberg, J; Ivarsson, S-A; Elding Larsson, H; Lernmark, Å

    2015-07-01

    Exposure to Ljungan virus (LV) is implicated in the risk of autoimmune (type 1) diabetes but possible contribution by other parechoviruses is not ruled out. The aim was to compare children diagnosed with type 1 diabetes in 2005-2011 (n = 69) with healthy controls (n = 294), all from the Jämtland County in Sweden, using an exploratory suspension multiplex immunoassay for IgM and IgG against 26 peptides of LV, human parechoviruses (HPeV), Aichi virus and poliovirus in relation to a radiobinding assay (RBA) for antibodies against LV and InfluenzaA/H1N1pdm09. Islet autoantibodies and HLA-DQ genotypes were also determined. 1) All five LV-peptide antibodies correlated to each other (P < 0.001) in the suspension multiplex IgM- and IgG-antibody assay; 2) The LV-VP1_31-60-IgG correlated with insulin autoantibodies alone (P = 0.007) and in combination with HLA-DQ8 overall (P = 0.022) as well as with HLA-DQ 8/8 and 8/X subjects (P = 0.013); 3) RBA detected LV antibodies correlated with young age at diagnosis (P < 0.001) and with insulin autoantibodies (P < 0.001) especially in young HLA-DQ8 subjects (P = 0.004); 4) LV-peptide-VP1_31-60-IgG correlated to RBA LV antibodies (P = 0.009); 5) HPeV3-peptide-IgM and -IgG showed inter-peptide correlations (P < 0.001) but only HPeV3-VP1_1-30-IgG (P < 0.001) and VP1_95-124-IgG (P = 0.009) were related to RBA LV antibodies without relation to insulin autoantibody positivity (P = 0.072 and P = 0.486, respectively). Both exploratory suspension multiplex IgG to LV-peptide VP1_31-60 and RBA detected LV antibodies correlated with insulin autoantibodies and HLA-DQ8 suggesting possible role in type 1 diabetes. It remains to be determined if cross-reactivity or concomitant exposure to LV and HPeV3 contributes to the seroprevalence.

  1. Atrophic coarctation of the abdominal aorta.

    Science.gov (United States)

    Wiest, J W; Traverso, L W; Dainko, E A; Barker, W F

    1980-01-01

    Two cases illustrate the clinical manifestations and angiographic findings associated with segmental stenosis of the abdominal aorta. Such lesions represent the chronic occlusive stage of Takayasu's disease, a nonspecific inflammatory arteritis of uncertain etiology. While the disease is considered autoimmune, an infectious process may be involved. Complications typically associated with stenotic lesions of the abdominal aorta are secondary renal hypertension and ischemic symptoms secondary to vascular insufficiency. Surgical correction, the treatment of choice, has achieved excellent results for these well-localized lesions. Secondary renal hypertension was relieved by a spenorenal shunt and the disease has since been controlled with conservative management in the first patient. An aortofemoral bypass graft successfully alleviated the vascular insufficiency in the second patient, although the patient unfortunately expired from a refractory postoperative cardiac complication. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:6102453

  2. Prof.Shan Zhaowei's Experience in Treating Chronic Atrophic Gastritis

    Institute of Scientific and Technical Information of China (English)

    吴连恩; 杨建平

    2004-01-01

    @@ Having been engaged in clinical practice for 40 years,Prof. Shah Zhaowei of Jiangsu Provincial Hospital of Traditional Chinese Medicine is good at treating chronic atrophic gastritis (CAG). In clinical practice,he often pays great attention to the combination of TCM syndrome-differentiation with diseasedifferentiation as well as the combination of macroscopic differentiation with microscopic differentiation. The therapeutic method he adopts or the drugs he prescribes are both simple and clear,often leading to remarkably therapeutic results. The following is a brief introduction to his clinical experience on the treatment of chronic atrophic gastritis (CAG).

  3. MiR-27a rs895819 is involved in increased atrophic gastritis risk, improved gastric cancer prognosis and negative interaction with Helicobacter pylori

    Science.gov (United States)

    Xu, Qian; Chen, Tie-jun; He, Cai-yun; Sun, Li-ping; Liu, Jing-wei; Yuan, Yuan

    2017-01-01

    MiR-27a rs895819 is a loop-stem structure single nucleotide polymorphism affecting mature miR-27a function. In this study, we performed a comprehensive analysis about the association of rs895819 with gastric cancer risk and prognosis, atrophic gastritis risk, as well as the interactions with environmental factors. A total of 939 gastric cancer patients, 1,067 atrophic gastritis patients and 1,166 healthy controls were screened by direct sequencing and MALDI-TOF-MS. The association of rs895819 with clinical pathological parameters and prognostic survival in 357 gastric cancer patients was also been analyzed. The rs895819 variant genotype increased the risk for atrophic gastritis (1.58-fold) and gastric cancer (1.24-fold). While in stratified analysis, the risk effect was demonstrated more significantly in the female, age >60y, Helicobacter pylori (H. pylori) negative and non-drinker subgroups. Rs895819 and H. pylori showed an interaction effect for atrophic gastritis risk. In the survival analysis, the rs895819 AG heterozygosis was associated with better survival than the AA wild-type in the TNM stage I–II subgroup. In vitro study by overexpressing miR-27a, cells carrying polymorphic-type G allele expressed lower miR-27a than wild-type A allele. In conclusion, miR-27a rs895819 is implicated as a biomarker for gastric cancer and atrophic gastritis risk, and interacts with H. pylori in gastric carcinogenesis. PMID:28150722

  4. Can the genetics of type 1 and type 2 diabetes shed light on the genetics of latent autoimmune diabetes in adults?

    Science.gov (United States)

    Grant, Struan F A; Hakonarson, Hakon; Schwartz, Stanley

    2010-04-01

    The pathophysiology of latent autoimmune diabetes in adults (LADA) is considered less understood than its much better characterized counterparts of type 1 and type 2 diabetes (T1D and T2D), where its clinical presentation exhibits some features of each of these two main diseases, earning it a reputation as being "type 1.5 diabetes". The etiology of LADA remains unknown, but a genetic component has been implicated from recent reports of T1D and T2D genes playing a role in its pathogenesis. One way to shed much needed light on the classification of LADA is to determine the discrete genetic factors conferring risk to the pathogenesis of this specific phenotype and to determine to what extent LADA shares genetic similarities with T1D and T2D. For instance, no conclusive support for a role of the T1D-associated INS gene has been reported in T2D; conversely, but similarly, no evidence has been found for the role of the T2D-associated genes IDE/HHEX, SLC30A8, CDKAL1, CDKN2A/B, IGF2BP2, FTO, and TCF7L2 in T1D. However, and somewhat at odds with current thinking, TCF7L2, the most strongly associated gene with T2D to date, is strongly associated with LADA, a disorder considered by the World Health Organization to be a slowly progressing form of T1D. In this review, we address recent advances in the genetics of T1D and T2D and how such discoveries have in turn shed some light on the genetics of LADA as being potentially at the "genetic intersection" of these two major diseases.

  5. Luminescent Immunoprecipitation System (LIPS) for Detection of Autoantibodies Against ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase in Atrophic Body Gastritis Patients

    Science.gov (United States)

    Lahner, Edith; Brigatti, Cristina; Marzinotto, Ilaria; Carabotti, Marilia; Scalese, Giulia; Davidson, Howard W; Wenzlau, Janet M; Bosi, Emanuele; Piemonti, Lorenzo; Annibale, Bruno; Lampasona, Vito

    2017-01-01

    Objectives: Circulating autoantibodies targeting the H+/K+-ATPase proton pump of gastric parietal cells are considered markers of autoimmune gastritis, whose diagnostic accuracy in atrophic body gastritis, the pathological lesion of autoimmune gastritis, remains unknown. This study aimed to assess autoantibodies against ATP4A and ATP4B subunits of parietal cells H+, K+-ATPase in atrophic body gastritis patients and controls. Methods: One-hundred and four cases with atrophic body gastritis and 205 controls were assessed for serological autoantibodies specific for ATP4A or ATP4B subunits using luminescent immunoprecipitation system (LIPS). Recombinant luciferase-reporter-fused-antigens were expressed by in vitro transcription-translation (ATP4A) or after transfection in Expi293F cells (ATP4B), incubated with test sera, and immune complexes recovered using protein-A-sepharose. LIPS assays were compared with a commercial enzyme immunoassay (EIA) for parietal cell autoantibodies. Results: ATP4A and ATP4B autoantibody titers were higher in cases compared to controls (Pgastritis. Both assays had the highest sensitivity, at the cost of diagnostic accuracy (89 and 90% specificity), outperforming traditional EIA. Once validated, these LIPS assays should be valuable screening tools for detecting biomarkers of damaged atrophic oxyntic mucosa. PMID:28102858

  6. Epigenomics of autoimmune diseases.

    Science.gov (United States)

    Gupta, Bhawna; Hawkins, R David

    2015-03-01

    Autoimmune diseases are complex disorders of largely unknown etiology. Genetic studies have identified a limited number of causal genes from a marginal number of individuals, and demonstrated a high degree of discordance in monozygotic twins. Studies have begun to reveal epigenetic contributions to these diseases, primarily through the study of DNA methylation, but chromatin and non-coding RNA changes are also emerging. Moving forward an integrative analysis of genomic, transcriptomic and epigenomic data, with the latter two coming from specific cell types, will provide an understanding that has been missed from genetics alone. We provide an overview of the current state of the field and vision for deriving the epigenomics of autoimmunity.

  7. Autoimmunity and Asbestos Exposure

    Directory of Open Access Journals (Sweden)

    Jean C. Pfau

    2014-01-01

    Full Text Available Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA, a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a a lack of statistical power due to relatively small or diffuse exposure cohorts, (b exposure misclassification, (c latency of clinical disease, (d mild or subclinical entities that remain undetected or masked by other pathologies, or (e effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.

  8. Autoimmune movement disorders.

    Science.gov (United States)

    Mckeon, Andrew; Vincent, Angela

    2016-01-01

    Autoimmune movement disorders encapsulate a large and diverse group of neurologic disorders occurring either in isolation or accompanying more diffuse autoimmune encephalitic illnesses. The full range of movement phenomena has been described and, as they often occur in adults, many of the presentations can mimic neurodegenerative disorders, such as Huntington disease. Disorders may be ataxic, hypokinetic (parkinsonism), or hyperkinetic (myoclonus, chorea, tics, and other dyskinetic disorders). The autoantibody targets are diverse and include neuronal surface proteins such as leucine-rich, glioma-inactivated 1 (LGI1) and glycine receptors, as well as antibodies (such as intracellular antigens) that are markers of a central nervous system process mediated by CD8+ cytotoxic T cells. However, there are two conditions, stiff-person syndrome (also known as stiff-man syndrome) and progressive encephalomyelitis with rigidity and myoclonus (PERM), that are always autoimmune movement disorders. In some instances (such as Purkinje cell cytoplasmic antibody-1 (PCA-1) autoimmunity), antibodies detected in serum and cerebrospinal fluid can be indicative of a paraneoplastic cause, and may direct the cancer search. In other instances (such as 65kDa isoform of glutamic acid decarboxylase (GAD65) autoimmunity), a paraneoplastic cause is very unlikely, and early treatment with immunotherapy may promote improvement or recovery. Here we describe the different types of movement disorder and the clinical features and antibodies associated with them, and discuss treatment.

  9. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus

    2010-01-01

    Autoimmune hypophysitis (AH) - often referred to as lymphocytic hypophysitis - is a rare disease that affects the pituitary gland and causes inflammation. The disease enlarges the pituitary gland and the clinical presentations are lack of pituitary function and headaches. AH is mostly seen in women...... 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...

  10. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005164 Optimal cut-point of glutamic acid decar-boxylase antibody (GAD-Ab) for differentiating two subtypes of latent autoimmune diabetes in adults (LADA). LI Xia(李霞), et al. Dept Endocrinol, 2nd Xiangya Hosp, Central South Univ, Changsha, 410011. Chin J Diabetes, 2005;13(1) :34-38. Objective: To investigate the optimal cut-point of glutamate decarboxylase antibody (GAD-Ab) for differentiating two subtypes of latent autoimmune diabetes in adults (I. ADA). Methods: The frequency

  11. TISSUE INHIBITOR OF METALLOPROTEINASE 1, MATRIX METALLOPROTEINASE 9, ALPHA-1 ANTITRYPSIN, METALLOTHIONEIN AND UROKINASE TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN SKIN BIOPSIES FROM PATIENTS AFFECTED BY AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-07-01

    Full Text Available Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for alpha-1-antitrypsin, human matrix metalloproteinase 9 (MMP9, human tissue inhibitor of metalloproteinases 1 (TIMP-1, metallothionein and urokinase type plasminogen activator receptor (uPAR. We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH. Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.

  12. [Autoimmunity factor in chronic gastritis: incidence of antiparietal cell antibodies and their relation to antral histology and basal blood gastrins].

    Science.gov (United States)

    Schraier, M; Katz, S; Pest, S; Chiocca, J C; Costa, J A

    1983-01-01

    In 118 patients with histological proven chronic gastritis, was performed a study of seric antibodies against parietal cells (ACCP), following the indirect inmuno-fluorescence method. The results were positives in 36 cases (30%). Four positives cases were found in 40 normal controls (10%), two of them were compensated diabetics, one have the thyrohyoid Hashimoto's disease, and the remainder, brother of a patient with chronic gastritis, was a positive ACCP. A major positiveness (44.4%) was obtained in 9 cases of gastric atrophy than in 65 cases with atrophic gastritis (32%) and in 44 cases of superficial gastritis (25%); although due to the few cases of gastric atrophy regarding other histological types, conclusions cannot be obtained about the incidence of ACCP and histological variety of chronic gastritis. If we do group the patients according to their acid secretory debit, 53 achlorhydric patients had a positiveness of ACCP of 45%, while over 63 with decreased secretory capability, only 18.4%, was positive. The distribution by age groups, shows a major incidence of ACCP about the 4th and 5th decade of life. Thirty seven patients with chronic atrophic gastritis and achlorhydria, and seven with chronic superficial gastritis and hypochlorhydria, besides the antibodies study were on a basal dosage of gastrinemia and antral endoscopic biopsy, finding out that, achlorhydric patients (15 on 19) with normal or slightly altered antrus, have gastrinemia (222 +/- 123 Pgo/oo) and the majority of patients with normal gastrinemia (32 +/- 16 pgo/oo) have more important antral lesions. The ratio between antral histology and ACCP in auto--immune gastritis (Type A), conciliates only partially with the observation by Strickland et al., as only 52.4% of achlorhydric patients and ACCP have a normal antrus or al least with mild lesions. Our results suggest the possibility of that on auto--immune gastritis could act other pathogenic factors of antral lesion.

  13. Multiple autoimmune syndrome with celiac disease.

    Science.gov (United States)

    Harpreet, Singh; Deepak, Jain; Kiran, B

    2016-01-01

    Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren's syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients.

  14. Thyroid autoimmunity and polyglandular endocrine syndromes.

    Science.gov (United States)

    Wémeau, Jean-Louis; Proust-Lemoine, Emmanuelle; Ryndak, Amélie; Vanhove, Laura

    2013-01-01

    Even though autoimmune thyroiditis is considered as the most emblematic type of organ-specific autoimmune disorder of autoimmunity, autoimmune thyroid diseases can be associated with other autoimmune endocrine failures or non-endocrine diseases (namely vitiligo, pernicious anemia, myasthenia gravis, autoimmune gastritis, celiac disease, hepatitis). Thyroid disorders, which are the most frequent expression of adult polyendocrine syndrome type 2, occur concomitantly with or secondarily to insulinodependent diabetes, premature ovarian failure, Addison's disease (Schmidt syndrome, or Carpenter syndrome if associated with diabetes). Testicular failure and hypoparathyroidism are unusual. The disease is polygenic and multifactorial. Disorders of thyroid autoimmunity are, surprisingly, very rare in polyendocrine syndrome type 1 (or APECED) beginning during childhood. They are related to mutations of the AIRE gene that encodes for a transcriptional factor implicated in central and peripheral immune tolerance. Hypothyroidism can also be observed in the very rare IPEX and POEMS syndromes.

  15. Autoimmune diseases and myelodysplastic syndromes.

    Science.gov (United States)

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation.

  16. Similarity of HLA-DQ profiles in adult-onset type 1 insulin-dependent diabetic patients with and without extra-pancreatic auto-immune disease.

    Science.gov (United States)

    Gu, X F; Larger, E; Clauser, E; Assan, R

    1992-01-01

    Some insulin-dependent diabetic patients present with auto-immune diseases involving extra pancreatic tissues (type 1b diabetes mellitus). The genetic specificity of this syndrome, as opposed to insulin dependent diabetes mellitus (IDDM) free of such associations (Type 1a IDDM) is not clearly established. We have analyzed the HLA-DQB1 and DQA1, loci, after PCR amplification of genomic DNA, in 44 Type 1b IDDM patients, 78 Type 1a IDDM patients and 105 control subjects. No essential difference in HLA-DQ profiles appeared between Type 1b and Type 1a IDDM patients. Both diabetic groups displayed a significant enrichment in DQB1 alleles negative for aspartate at position 57 (Type 1b: 83%; Type 1a: 89%; controls 48%; p < 0.001 vs both patient groups) and in DQB1 Asp 57 negative homozygosity: 71% of Type 1b; 80% of Type 1a; 25% of controls (p < 0.01). This enrichment in DQB1 Asp 57 negative alleles was accounted for by DQB1* 0201 in the Type 1b group, and by DQB1 % 0201 and 0302 in the Type 1a patients. Conversely, alleles DQB1* 0602 and 0301 (DQB1 Asp 57 positive) were protective. Both diabetic groups also displayed a significant enrichment in DQA1 alleles positives for arginine at position 52 (65% of Type 1b; 76% of Type 1a; 50% of control subjects; p < 0.01 and 0.001, respectively, vs controls), and in DQA1 Arg 52 positive homozygotes (48% of Type 1b, 58% of Type 1a, 22% of control subjects; p < 0.01). All differences between diabetic groups and the control group were more pronounced in the case of Type 1a than of Type 1b patients. The HLA-DQ genes shared by Type 1a and Type 1b patients must therefore be closely associated with islet autoimmunity. Genetic differences between Type 1a and Type 1b syndromes, if any, must be investigated in other MHC and non-MHC regions of the genome.

  17. Autoimmune sialadenitis

    NARCIS (Netherlands)

    Guntinas-Lichius, O.; Vissink, A.; Ihrler, S.

    2010-01-01

    Using the European-American classification criteria the diagnosis of autoimmune sialadenitis in Sjogren's syndrome can generally be easily established or excluded. In addition, sonography performed by the ENT physician is helpful in diagnosing and especially in follow-up screening for MALT lymphomas

  18. The role of dendritic cell subsets and innate immunity in the pathogenesis of type 1 diabetes and other autoimmune diseases

    OpenAIRE

    Price, Jeffrey D; Tarbell, Kristin V.

    2015-01-01

    Dendritic cells (DCs) are key antigen presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, ...

  19. The Role of Dendritic Cell Subsets and Innate Immunity in the Pathogenesis of Type 1 Diabetes and Other Autoimmune Diseases

    OpenAIRE

    Price, Jeffrey D; Tarbell, Kristin V.

    2015-01-01

    Dendritic cells (DCs) are key antigen-presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, ...

  20. Autoimmune paediatric liver disease

    Institute of Scientific and Technical Information of China (English)

    Giorgina Mieli-Vergani; Diego Vergani

    2008-01-01

    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 distinct entity or a form of

  1. Fractional CO 2 laser resurfacing as monotherapy in the treatment of atrophic facial acne scars

    Directory of Open Access Journals (Sweden)

    Imran Majid

    2014-01-01

    Full Text Available Background: While laser resurfacing remains the most effective treatment option for atrophic acne scars, the high incidence of post-treatment adverse effects limits its use. Fractional laser photothermolysis attempts to overcome these limitations of laser resurfacing by creating microscopic zones of injury to the dermis with skip areas in between. Aim: The aim of the present study is to assess the efficacy and safety of fractional CO 2 laser resurfacing in atrophic facial acne scars. Materials and Methods: Sixty patients with moderate to severe atrophic facial acne scars were treated with 3-4 sessions of fractional CO 2 laser resurfacing at 6-week intervals. The therapeutic response to treatment was assessed at each follow up visit and then finally 6 months after the last laser session using a quartile grading scale. Response to treatment was labelled as ′excellent′ if there was >50% improvement in scar appearance and texture of skin on the grading scale while 25-50% response and <25% improvement were labelled as ′good′ and ′poor′ response, respectively. The overall satisfaction of the patients and any adverse reactions to the treatment were also noted. Results: Most of the patients showed a combination of different morphological types of acne scars. At the time of final assessment 6 months after the last laser session, an excellent response was observed in 26 patients (43.3% while 15 (25% and 19 patients (31.7% demonstrated a good and poor response respectively. Rolling and superficial boxcar scars responded the best while pitted scars responded the least to fractional laser monotherapy. The commonest reported adverse effect was transient erythema and crusting lasting for an average of 3-4 and 4-6 days, respectively while three patients developed post-inflammatory pigmentation lasting for 8-12 weeks. Conclusions: Fractional laser resurfacing as monotherapy is effective in treating acne scars especially rolling and superficial boxcar

  2. ASSESSMENT OF MICRONEEDLING THERAPY IN THE MANAGEMENT OF ATROPHIC FACIAL ACNE SCARS

    Directory of Open Access Journals (Sweden)

    Ajay

    2015-12-01

    Full Text Available STUDY BACKGROUND Post acne scars are always a challenge to treat, especially the ones which are deep seated. There are many treatment options like laser resurfacing, dermabrasion, microdermabrasion and non-ablative laser resurfacing but with considerable morbidity and interference with the daily activities of the patient in the post-treatment period. Microneedling or dermaroller therapy is one of the new treatment options in the management of acne scars with satisfactory improvement and no significant side effect. The aim of the present study is to perform an objective evaluation the efficacy of microneedling in the treatment of atrophic acne scars. MATERIALS AND METHODS Thirty patients of skin type III-V having atrophic facial acne scars presenting to our dermatology OPD. were received multiple sittings of microneedling (dermaroller treatment with an interval of 6 weeks between each session. Goodman & Baron’s acne scar grading system was used for assessment of their scars and was evaluated clinically by serial photography at the start as well as at two months after the conclusion of the treatment. Patients on anticoagulant therapy, of keloidal tendency, with bleeding disorders, vitiligo patients, pregnant and lactating mothers and patients with active acne lesions were excluded from the study. The duration of this study was for ten months-from January 2014 to October 2014. RESULTS Any change in the grading of scars after the end of treatment and follow-up period was noted down. The efficacy and improvement of dermaroller treatment was assessed by Goodman and Baron’s Global Acne Scarring System. Out of 30 patients, 26(80.64% patients achieved a reduction in the severity of their scarring by one or two grades. Quantitative assessment showed that 13.3% of patients had minimal, 16.6% had good and 70% showed very good improvement. Adverse effects were limited to transient pain, erythema and edema. CONCLUSION Microneedling therapy seems to be

  3. Islet autoantibodies in Latvian subjects with non-insulin-dependent diabetes mellitus: slow-onset type 1 diabetes or polyendocrine autoimmunity?

    Science.gov (United States)

    Shtauvere-Brameus, A; Falorni, A; Rumba, I; Sanjeevi, C B

    2002-04-01

    In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria; assays for the detection of autoantibodies are not available, and hence slowly progressive autoimmune diabetes is likely to be missed. Autoantibodies against glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase (IA-2) among patients with clinically diagnosed NIDDM identify group of patients with slow-onset type 1 diabetes or LADA. The aim of this study was to estimate the risk of polyendocrine autoimmunity among clinically diagnosed NIDDM patients from Latvia. One hundred NIDDM patients and 100 healthy controls were tested for GAD65 and IA-2 autoantibodies as well as 21-hydroxylase (21-OH) and tissue transglutaminase (TTG) antibodies by RIA assay. Age at onset was >or= 30 years, and duration of disease less than 5 years. Of 100 patients, 85 were on oral hypoglycemic agents and 15 were on insulin. Body mass index (BMI) under 19 was recorded in 1% (1 of 100 cases), while overweight (BMI > 25.5 in females and 27 in males) was documented in 45% (45 of 100 cases). GAD65 antibodies were found in 30 of 100 (30%) and IA-2 antibodies in 40 of 100 (40%) patients. Either GAD65 or IA-2 antibodies were found in 55 of 100 (55%). None of the patients carried antibodies against 21-OH and only 1 of 100 (1%) carried antibodies against TTG. From the results obtained in our study we conclude that in Latvian adult NIDDM subjects, islet autoantibodies identify groups of slow-onset type 1 diabetes but not polyendocrine autoimmunity.

  4. WJD 5th Anniversary Special Issues(3): Type 1 diabetes Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Elena; Pipi; Marietta; Marketou; Alexandra; Tsirogianni

    2014-01-01

    Ever since its first appearance among the multiple forms of diabetes,latent autoimmune diabetes in adults(LADA),has been the focus of endless discussions concerning mainly its existence as a special type of diabetes.In this mini-review,through browsing important peer-reviewed publications,(original articles and reviews),we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity.A unique combination of immunological,clinical and metabolic characteristics has been identified in this group of patients,namely persistent islet cell antibodies,high frequency of thyroid and gastric autoimmunity,DR3 and DR4 human leukocyte antigen haplotypes,progressive loss of beta cells,adult disease onset,normal weight,defective glycaemic control,and without tendency to ketoacidosis.Although anthropomorphic measurements are useful as a first line screening,the detection of C-peptide levels and the presence of glutamic acid decarboxylase(GAD)autoantibodies is undoubtedly the sine qua non condi-tion for a confirmatory LADA diagnosis.In point of fact,GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied.Nevertheless,the lack of diagnostic criteria and guidelines still puzzle the physicians,who struggle between early diagnosis and correct timing for insulin treatment.

  5. Iodine and tri-iodo-thyronine reduce the incidence of type 1 diabetes mellitus in the autoimmune prone BB rats

    DEFF Research Database (Denmark)

    Hartoft-Nielsen, Marie-Louise; Rasmussen, Aase Krogh; Bock, Troels;

    2009-01-01

    Thyroid hormones modulate the immune system and metabolism, influence insulin secretion, and cause decreased glucose tolerance. Thyroid hormones have been described to change the incidence of spontaneous autoimmune thyroiditis in Bio-Breeding/Worcester (BB) rats but it is unknown how these hormones...... iodine (NaI) or thyroid stimulating hormone (TSH) neonatally or with tri-iodo-thyronine (T3) during adolescence. At the age of 19 weeks the incidence of T1DM and the degree of insulitis were evaluated. The influence of T3 treatment on the beta cell mass was evaluated in Wistar rats by unbiased...

  6. Autoimmune pancreatitis and cholangitis

    Institute of Scientific and Technical Information of China (English)

    Niraj; Jani; James; Buxbaum

    2015-01-01

    Autoimmune pancreatitis(AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4(Ig G4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreaticmanifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG 4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG 4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings.

  7. Painful linear atrophic lichen planus along lines of Blaschko

    Directory of Open Access Journals (Sweden)

    Lakshmi Chembolli

    2006-01-01

    Full Text Available Linear lichen planus along the lines of Blaschko is uncommon. Atrophic lichen planus is usually a sequel to resolving annular and ulcerative lesions. We herewith report a case of histopathologically proven lichen planus, presenting with atrophy at the outset, in a linear distribution along the lines of Blaschko. In addition to the cutaneous findings, she also had pain along the distribution of lesions.

  8. Combination therapy in the management of atrophic acne scars

    Directory of Open Access Journals (Sweden)

    Shilpa Garg

    2014-01-01

    Full Text Available Background: Atrophic acne scars are difficult to treat. The demand for less invasive but highly effective treatment for scars is growing. Objective: To assess the efficacy of combination therapy using subcision, microneedling and 15% trichloroacetic acid (TCA peel in the management of atrophic scars. Materials and Methods: Fifty patients with atrophic acne scars were graded using Goodman and Baron Qualitative grading. After subcision, dermaroller and 15% TCA peel were performed alternatively at 2-weeks interval for a total of 6 sessions of each. Grading of acne scar photographs was done pretreatment and 1 month after last procedure. Patients own evaluation of improvement was assessed. Results: Out of 16 patients with Grade 4 scars, 10 (62.5% patients improved to Grade 2 and 6 (37.5% patients improved to Grade 3 scars. Out of 22 patients with Grade 3 scars, 5 (22.7% patients were left with no scars, 2 (9.1% patients improved to Grade 1and 15 (68.2% patients improved to Grade 2. All 11 (100% patients with Grade 2 scars were left with no scars. There was high level of patient satisfaction. Conclusion: This combination has shown good results in treating not only Grade 2 but also severe Grade 4 and 3 scars.

  9. Serum Prohepcidin Levels Are Lower in Patients with Atrophic Gastritis

    Directory of Open Access Journals (Sweden)

    Hyung-Keun Kim

    2013-01-01

    Full Text Available Background/Aim. Hepcidin, an iron regulatory hormone, is increased in response to inflammation and some infections. We investigated the relationships among serum prohepcidin, iron status, Helicobacter pylori infection status, and the presence of gastric mucosal atrophy. Methods. Seventy subjects undergoing esophagogastroduodenoscopy underwent multiple gastric biopsies, and the possibility of H. pylori infection and the degree of endoscopic and histologic gastritis were investigated. In all subjects, serum prohepcidin and iron parameters were evaluated. Results. No correlations were observed between serum prohepcidin levels and the other markers of anemia, such as hemoglobin, serum iron, ferritin, and total iron binding capacity. Serum prohepcidin levels were not significantly different between the H. pylori-positive group and the H. pylori-negative group. Serum prohepcidin levels in atrophic gastritis patients were significantly lower than those in subjects without atrophic gastritis irrespective of H. pylori infection. Conclusion. Serum prohepcidin levels were not altered by H. pylori infection. Serum prohepcidin levels decrease in patients with atrophic gastritis, irrespective of H. pylori infection. It suggests that hepcidin may decrease due to gastric atrophy, a condition that causes a loss of hepcidin-producing parietal cells. Further investigations with a larger number of patients are necessary to substantiate this point.

  10. Serum prohepcidin levels are lower in patients with atrophic gastritis.

    Science.gov (United States)

    Kim, Hyung-Keun; Jang, Eun-Chul; Yeom, Ju-Ok; Kim, Sun-Young; Cho, Hyunjung; Kim, Sung Soo; Chae, Hiun-Suk; Cho, Young-Seok

    2013-01-01

    Background/Aim. Hepcidin, an iron regulatory hormone, is increased in response to inflammation and some infections. We investigated the relationships among serum prohepcidin, iron status, Helicobacter pylori infection status, and the presence of gastric mucosal atrophy. Methods. Seventy subjects undergoing esophagogastroduodenoscopy underwent multiple gastric biopsies, and the possibility of H. pylori infection and the degree of endoscopic and histologic gastritis were investigated. In all subjects, serum prohepcidin and iron parameters were evaluated. Results. No correlations were observed between serum prohepcidin levels and the other markers of anemia, such as hemoglobin, serum iron, ferritin, and total iron binding capacity. Serum prohepcidin levels were not significantly different between the H. pylori-positive group and the H. pylori-negative group. Serum prohepcidin levels in atrophic gastritis patients were significantly lower than those in subjects without atrophic gastritis irrespective of H. pylori infection. Conclusion. Serum prohepcidin levels were not altered by H. pylori infection. Serum prohepcidin levels decrease in patients with atrophic gastritis, irrespective of H. pylori infection. It suggests that hepcidin may decrease due to gastric atrophy, a condition that causes a loss of hepcidin-producing parietal cells. Further investigations with a larger number of patients are necessary to substantiate this point.

  11. Meningeal Tertiary Lymphoid Tissues and Multiple Sclerosis: A Gathering Place for Diverse Types of Immune Cells during CNS Autoimmunity.

    Science.gov (United States)

    Pikor, Natalia B; Prat, Alexandre; Bar-Or, Amit; Gommerman, Jennifer L

    2015-01-01

    Collections of leukocytes in the meningeal space have been documented in Multiple Sclerosis (MS). These meningeal aggregates, which in the context of other autoimmune diseases have often been termed tertiary lymphoid tissues (TLT), have been associated with sub-pial cortical damage and disease progression. However, the key molecular and cellular signals required for their formation and maintenance remain unclear. Herein, we review TLT structures in other disease states in order to provide a framework for understanding these structures in the MS meninges. We then assess the evidence that the meningeal compartment serves as an important nexus for immune cells as well as a location for drainage of antigen into cervical lymph nodes. Extrapolating what is known about the molecular and cellular cues that initiate the formation of leukocyte aggregates in non-lymphoid tissues, we speculate on what signals lead to the formation and maintenance of meningeal TLT structures. Referring to the animal model of MS [experimental autoimmune encephalomyelitis (EAE)], we also explore what is known about these structures in supporting B cell and T cell responses during neuroinflammation. Last, we examine the evidence that connects these structures to ongoing neuropathology. Collectively, our review points to the meningeal compartment as an important player in neuroinflammatory processes. Moreover, we hypothesize that in order to gain insights into pro- and anti-inflammatory properties of lymphocytes in MS, one must understand the cellular scaffolds that support lymphocyte retention within the meninges, thus highlighting the importance of non-immune cells (stromal cells) in the neuroinflammatory process.

  12. A two-short-implant-supported molar restoration in atrophic posterior maxilla: A finite element analysis

    Science.gov (United States)

    2016-01-01

    PURPOSE The aim of this study was to investigate the stress distribution of 2-short implants (2SIs) installed in a severely atrophic maxillary molar site. MATERIALS AND METHODS Three different diameters of internal connection implants were modeled: narrow platform (NP), regular platform (RP), and wide platform (WP). The maxillary first molars were restored with one implant or two short implants. Three 2SI models (NP-oblique, NP-vertical, and NP-horizontal) and four single implant models (RP and WP in a centered or cantilevered position) were used. Axial and oblique loadings were applied on the occlusal surface of the crown. The von Mises stress values were measured at the bone-implant, peri-implant bone, and implant/abutment complex. RESULTS The highest stress distribution at the bone-implant interface and the peri-implant bone was noticed in the RP group, and the lowest stress distribution was observed in the 2SI groups. Cantilevered position showed unfavorable stress distribution with axial loading. 2SI types did not affect the stress distribution in oblique loading. The number and installation positions of the implant, rather than the bone level, influenced the stress distribution of 2SIs. The implant/abutment complex of WP presented the highest stress concentration while that of 2SIs showed the lowest stress concentration. CONCLUSION 2SIs may be useful for achieving stable stress distribution on the surrounding bone and implant-abutment complex in the atrophic posterior maxilla. PMID:27555900

  13. Protean manifestations of vitamin D deficiency, part 2: deficiency and its association with autoimmune disease, cancer, infection, asthma, dermopathies, insulin resistance, and type 2 diabetes.

    Science.gov (United States)

    Bell, David S H

    2011-05-01

    Vitamin D deficiency is epidemic and its manifestations are protean. Vitamin D deficiency is associated with autoimmune diseases (particularly multiple sclerosis and type 1 diabetes) and has been associated with infection, allergy, asthma, and dermopathies (particularly psoriasis). Asthma may be worsened by vitamin D deficiency and correction of the deficiency has been shown to improve the manifestations of asthma. Vitamin D deficiency has been associated with multiple cancers, including those of the breast, colon, ovary, and prostate. Due mainly to increased insulin resistance but also to an impairment in insulin release, vitamin D deficiency is associated with the development of type 2 diabetes. In addition, the complications of diabetes may be worsened by vitamin D deficiency.

  14. Autoimmune liver disease panel

    Science.gov (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 cirrhosis. This group of tests helps your health care provider ...

  15. Reversal of type 1 diabetes by a new MHC II-peptide chimera: "Single-epitope-mediated suppression" to stabilize a polyclonal autoimmune T-cell process.

    Science.gov (United States)

    Lin, Marvin; Stoica-Nazarov, Cristina; Surls, Jacqueline; Kehl, Margaret; Bona, Constantin; Olsen, Cara; Brumeanu, Teodor D; Casares, Sofia

    2010-08-01

    Polyclonality of self-reactive CD4(+) T cells is the hallmark of several autoimmune diseases like type 1 diabetes. We have previously reported that a soluble dimeric MHC II-peptide chimera prevents and reverses type 1 diabetes induced by a monoclonal diabetogenic T-cell population in double Tg mice [Casares, S. et al., Nat. Immunol. 2002. 3: 383-391]. Since most of the glutamic acid decarboxylase 65 (GAD65)-specific CD4(+) T cells in the NOD mouse are tolerogenic but unable to function in an autoimmune environment, we have activated a silent, monoclonal T-regulatory cell population (GAD65(217-230)-specific CD4(+) T cells) using a soluble I-A(αβ) (g7)/GAD65(217-230)/Fcγ2a dimer, and measured the effect on the ongoing polyclonal diabetogenic T-cell process. Activated GAD65(217-230)-specific T cells and a fraction of the diabetogenic (B(9-23)-specific) T cells were polarized toward the IL-10-secreting T-regulatory type 1-like function in the pancreas of diabetic NOD mice. More importantly, this led to the reversal of hyperglycemia for more than 2 months post-therapy in 80% of mice in the context of stabilization of pancreatic insulitis and improved insulin secretion by the β cells. These findings argue for the stabilization of a polyclonal self-reactive T-cell process by a single epitope-mediated bystander suppression. Dimeric MHC class II-peptide chimeras-like approach may provide rational grounds for the development of more efficient antigen-specific therapies in type 1 diabetes.

  16. HLA B44 is associated with decreased severity of autoimmune lymphoproliferative syndrome in patients with CD95 defects (ALPS type Ia).

    Science.gov (United States)

    Vacek, Marla M; Schäffer, Alejandro A; Davis, Joie; Fischer, Roxanne E; Dale, Janet K; Adams, Sharon; Straus, Stephen E; Puck, Jennifer M

    2006-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte apoptosis characterized by non-malignant lymphadenopathy and splenomegaly, expansion of T cells without either CD4 or CD8 surface markers, and increased incidence of autoimmune diseases and lymphoma. Most patients with ALPS have dominant, heterozygous mutations in tumor necrosis factor receptor superfamily member 6 (TNFRSF6), which encodes CD95, also known as Fas, a mediator of apoptosis. Penetrance and range of disease manifestations in ALPS are highly variable, even among family members who share the same dominant TNFRSF6 mutation. To evaluate HLA as a candidate modifier locus, we typed HLA A, B (including subtypes), and DQB alleles in 356 individuals from 63 unrelated families with defined TNFRSF6 mutations associated with ALPS. We also developed a quantitative severity score and performed statistical analysis. Among the healthier, mutation-bearing individuals, transmission of HLA B44 was significantly overrepresented (nominal PALPS. The B44 allele may exert a protective role in ALPS.

  17. Meningeal Tertiary Lymphoid Tissues and Multiple Sclerosis: A gathering place for diverse types of Immune Cells during CNS autoimmunity

    Directory of Open Access Journals (Sweden)

    Natalia ePikor

    2016-01-01

    Full Text Available Collections of leukocytes in the meningeal space have been documented in Multiple Sclerosis (MS. These meningeal aggregates, which in the context of other autoimmune diseases have often been termed Tertiary Lymphoid Tissues (TLT, have been associated with sub-pial cortical damage and disease progression. However, the key molecular and cellular signals required for their formation and maintenance, remain unclear. Herein we review TLT structures in other disease states in order to provide a framework for understanding these structures in the MS meninges. We then assess the evidence that the meningeal compartment serves as an important nexus for immune cells as well as a location for drainage of antigen into the cervical lymph node compartment. Extrapolating what is known about the molecular and cellular cues that initiate the formation of leukocyte aggregates in non-lymphoid tissues, we speculate on what signals lead to the formation and maintenance of meningeal TLT structures. Referring to the animal model of MS (Experimental Autoimmune Encephalomyelitis - EAE, we also explore what is known about these structures in supporting B cell and T cell responses during neuroinflammation. Lastly, we examine the evidence that connects these structures to ongoing neuropathology. Collectively, our review points to the meningeal compartment as an important player in neuroinflammatory processes. Moreover, we hypothesize that in order to gain insights into pro- and anti-inflammatory properties of lymphocytes in MS, one must understand the cellular scaffolds that support lymphocyte retention within the meninges, thus highlighting the importance of non-immune cells (stromal cells in the neuroinflammatory process.

  18. Role of Complement in Autoimmune Hemolytic Anemia

    OpenAIRE

    Berentsen, Sigbjørn

    2015-01-01

    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorder...

  19. Severe autoimmune hemolytic anemia with renal neoplasm.

    Science.gov (United States)

    Rhodes, Emily C; Parikh, Sahil P; Bhattacharyya, Nishith

    2014-02-01

    Autoimmune hemolytic anemia is a type of hemolytic anemia characterized by autoantibodies directed against red blood cells shortening their survival. When autoimmune hemolytic anemia is secondary to a paraneoplastic process, severe anemia can occur leading to significant morbidity and even mortality. Here we discuss the literature and present the case of a child with autoimmune hemolytic anemia from a paraneoplastic syndrome secondary to a renal tumor.

  20. Evidence of Stage- and Age-Related Heterogeneity of Non-HLA SNPs and Risk of Islet Autoimmunity and Type 1 Diabetes: The Diabetes Autoimmunity Study in the Young

    Directory of Open Access Journals (Sweden)

    Brittni N. Frederiksen

    2013-01-01

    Full Text Available Previously, we examined 20 non-HLA SNPs for association with islet autoimmunity (IA and/or progression to type 1 diabetes (T1D. Our objective was to investigate fourteen additional non-HLA T1D candidate SNPs for stage- and age-related heterogeneity in the etiology of T1D. Of 1634 non-Hispanic white DAISY children genotyped, 132 developed IA (positive for GAD, insulin, or IA-2 autoantibodies at two or more consecutive visits; 50 IA positive children progressed to T1D. Cox regression was used to analyze risk of IA and progression to T1D in IA positive children. Restricted cubic splines were used to model SNPs when there was evidence that risk was not constant with age. C1QTNF6 (rs229541 predicted increased IA risk (HR: 1.57, CI: 1.20–2.05 but not progression to T1D (HR: 1.13, CI: 0.75–1.71. SNP (rs10517086 appears to exhibit an age-related effect on risk of IA, with increased risk before age 2 years (age 2 HR: 1.67, CI: 1.08–2.56 but not older ages (age 4 HR: 0.84, CI: 0.43–1.62. C1QTNF6 (rs229541, SNP (rs10517086, and UBASH3A (rs3788013 were associated with development of T1D. This prospective investigation of non-HLA T1D candidate loci shows that some SNPs may exhibit stage- and age-related heterogeneity in the etiology of T1D.

  1. Pure red cell aplasia accompanied by autoimmune hemolytic anemia in a patient with type A viral hepatitis.

    Science.gov (United States)

    Koiso, Hiromi; Kobayashi, Satsuki; Ueki, Kazue; Hamada, Tetsuya; Tsukamoto, Norifumi; Karasawa, Masamitsu; Murakami, Hirokazu; Nojima, Yoshihisa

    2009-05-01

    A rare case of acute hepatitis A associated with autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) is reported. A 55-year-old woman consulted a doctor because of common cold-like symptoms and she was referred to our hospital in January 2007. Laboratory findings showed a marked elevation of serum transaminase and total bilirubin levels (AST 9,605 IU/l, ALT 5,546 IU/l and T-bil 4.14 mg/dl), and prolonged prothrombin time, findings which suggested the risk of progression to fulminant hepatitis, and she was treated with plasmapheresis and hemodialysis filtration on the first and second hospital days. She was diagnosed with severe acute hepatitis A based on the elevation of serum IgM anti-hepatitis A virus. On the 20th hospital day, her hemoglobin level began to decrease in spite of improving transaminase levels without any signs of gastrointestinal bleeding. Bilirubin and LDH elevation, haptoglobin decline and a positive direct Coombs test were detected and these findings indicated AIHA complication; however, the reticulocyte count decreased and bone marrow showed marked erythroid hypoplasia so the co-existence of PRCA was diagnosed. After oral prednisolone administration (1 mg/kg/day), her hemolytic anemia rapidly improved.

  2. HLA-DR-positive cells in large plaque (atrophic) parapsoriasis.

    Science.gov (United States)

    McMillan, E M; Wasik, R; Everett, M A

    1981-10-01

    The development of a monoclonal antibody directed against HLA DR (Ia-like) antigens of B cells and monocytes but not against normal peripheral human T cells suggested that this antibody might be used as a marker of B cells and monocytes in tissue sections. The T cell nature of large plaque (atrophic) parapsoriasis has recently been demonstrated by the immunoperoxidase technic. Immunoperoxidase examination of serial sections of tissues from two cases of large plaque parapsoriasis with one T cell antiserum, two monoclonal T cell antibodies, and one monoclonal reagent directed against HLA DR indicated that T cells in the cutaneous infiltrates were also HLA DR-positive. Evidence is accumulating that HLA DR positivity may be expressed by activated T cells. The findings here therefore suggest that many of the T lymphoid cells in two cases of large plaque (atrophic) parapsoriasis examined were activated in nature, and that HLA DR may not be a specific marker for B cells and monocytes in certain pathologic conditions. Caution should therefore presently be exercised in attempting to use this marker for the specific identification of B cells and monocytes in pathologic specimens, without simultaneous testing for T cell markers.

  3. Paradigm Shift in the Management of the Atrophic Posterior Maxilla

    Directory of Open Access Journals (Sweden)

    Rabah Nedir

    2014-01-01

    Full Text Available When the posterior maxilla is atrophic, the reference standard of care would be to perform sinus augmentation with an autologous bone graft through the lateral approach and delayed implant placement. However, placement of short implants with the osteotome sinus floor elevation technique and without graft can be proposed for an efficient treatment of clinical cases with a maxillary residual bone height of 4 to 8 mm. The use of grafting material is recommended only when the residual bone height is ≤4 mm. Indications of the lateral sinus floor elevation are limited to cases with a residual bone height ≤ 2 mm and fused corticals, uncompleted healing of the edentulous site, and absence of flat cortical bone crest or when the patient wishes to wear a removable prosthesis during the healing period. The presented case report illustrates osteotome sinus floor elevation with and without grafting and simultaneous implant placement in extreme conditions: atrophic maxilla, short implant placement, reduced healing time, and single crown rehabilitation. After 6 years, all placed implants were functional with an endosinus bone gain.

  4. Diabetes mellitus tipo 1: multifatores que conferem suscetibilidade à patogenia auto-imune = Type 1 diabetes mellitus: multifactors that confer susceptibility to the autoimmune pathogenesis

    Directory of Open Access Journals (Sweden)

    Staub, Henrique Luiz

    2007-01-01

    Full Text Available Objetivos: revisar dados de literatura concernentes aos fatores que conferem suscetibilidade à patogenia auto-imune do diabetes mellitus tipo 1. Fonte de dados: revisão de artigos especializados no assunto publicados em bancos de dados nacionais e internacionais (SCIELO, LILACS e PUBMED. Síntese de dados: a etiopatogenia do diabetes mellitus tipo 1 está associada a fatores inflamatórios, genéticos e ambientais. Nesta revisão, abordamos o papel da auto-imunidade humoral e celular que culmina com a disfunção das células-beta produtoras de insulina. A precocidade da presença de alguns autoanticorpos como anti-ilhotas pancreáticas, antiinsulina e anti-ácido glutâmico descarboxilase é uma característica importante nesta patologia. Os diversos fatores genéticos associados ao deflagramento do diabetes mellitus tipo 1, sobretudo os associados ao sistema de antígenos leucocitários humanos, acabam por potencializar a apresentação de antígenos das ilhotas para o sistema imune. Por fim, fatores ambientais como exposição viral também contribuem para a quebra de tolerância imunológica observada nesses pacientes. Conclusões: o diabetes mellitus tipo 1 é uma entidade de etiopatogenia altamente complexa. Diversos fatores genéticos e ambientais potencializam os mecanismos de auto-imunidade humoral e celular que levam à insulite. O risco de hipoglicemia severa observada com o tratamento insulínico e as complicações crônicas do diabetes mellitus tipo 1 justificam pesquisas contínuas em relação à etiopatogenia desta entidade, o que contribuirá para abordagens terapêuticas mais eficazes. Aims: To review the literature data concerning the factors which confer susceptibilitiy to the autoimmune pathogenesis of type I diabetes mellitus. Source of data: Review of specific articles on the issue published in national and in-ternational databases (SCIELO, LILACS, PUBMED. Summary of the findings: The etiopathogenesis of type I diabetes

  5. Development of mixed-type autoimmune hemolytic anemia and Evans' syndrome following chicken pox infection in a case of low-titer cold agglutinin disease.

    Science.gov (United States)

    Tanaka, Yumi; Masuya, Masahiro; Katayama, Naoyuki; Miyata, Eri; Sugimoto, Yuka; Shibasaki, Tetsunori; Yamamura, Kentaro; Ohishi, Kohshi; Minami, Nobuyuki; Shiku, Hiroshi; Nobori, Tsutomu

    2006-10-01

    We describe a patient with low-titer cold agglutinin disease (CAD) who developed mixed-type autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenia following chicken pox infection. At least 1 year before admission to hospital, the patient had mild hemolytic anemia associated with low-titer cold agglutinins. A severe hemolytic crisis and thrombocytopenia (Evans' syndrome) occurred several days after infection with chicken pox, and the patient was referred to our hospital. Serological findings revealed the presence of both cold agglutinins and warm-reactive autoantibodies against erythrocytes, and the diagnosis was mixed-type AIHA. Following steroid therapy, the hemoglobin (Hb) level and platelet count improved. The patient was closely followed over a 10-year period with recurrent documented hemolysis after viral or bacterial infections. Warm-reactive autoantibodies have not been detected in the last 2 years, and only the immunoglobulin M anti-I cold agglutinins with a low titer and wide thermal amplitude have remained unchanged. Therefore, the patient has received at least 10 mg prednisolone daily to maintain a Hb level of 10 g/dL. To the best of our knowledge, no adult case of low-titer CAD that has evolved into mixed-type AIHA and Evans' syndrome after chicken pox infection has been previously reported in the literature.

  6. Novel feline autoimmune blistering disease resembling bullous pemphigoid in humans: IgG autoantibodies target the NC16A ectodomain of type XVII collagen (BP180/BPAG2).

    Science.gov (United States)

    Olivry, T; Chan, L S; Xu, L; Chace, P; Dunston, S M; Fahey, M; Marinkovich, M P

    1999-07-01

    In humans and dogs, bullous pemphigoid (BP) is an autoimmune blistering disease associated with the production of basement membrane autoantibodies that target the 180-kd type XVII collagen (BP180, BPAG2) and/or the 230-kd plakin epidermal isoform BPAG1e (BP230). In two adult cats, an acquired dermatosis and stomatitis was diagnosed as BP subsequent to the fulfillment of the following criteria: 1) presence of cutaneous vesicles, erosions, and ulcers; 2) histologic demonstration of subepidermal vesiculation with inflammatory cells, including eosinophils; 3) in vivo deposition of IgG autoantibodies at the epidermal basement membrane zone; and 4) serum IgG autoantibodies targeting a 180-kd epidermal protein identified as type XVII collagen. In both cats, the antigenic epitopes targeted by IgG autoantibodies were shown to be situated in the NC16A ectodomain of type XVII collagen, a situation similar to that of humans and dogs with BP. Feline BP therefore can be considered a clinical, histopathologic, and immunologic homologue of BP in humans and dogs.

  7. Experimental autoimmune myasthenia gravis may occur in the context of a polarized Th1- or Th2-type immune response in rats

    DEFF Research Database (Denmark)

    Saoudi, A; Bernard, I; Hoedemaekers, A

    1999-01-01

    Experimental autoimmune myasthenia gravis (EAMG) is a T cell-dependent, Ab-mediated autoimmune disease induced in rats by a single immunization with acetylcholine receptor (AChR). Although polarized Th1 responses have been shown to be crucial for the development of mouse EAMG, the role of Th cell...

  8. The autoimmune tautology.

    Science.gov (United States)

    Anaya, Juan-Manuel

    2010-01-01

    Although autoimmune diseases exhibit contrasting epidemiological features, pathology, and clinical manifestations, three lines of evidence demonstrate that these diseases share similar immunogenetic mechanisms (that is, autoimmune tautology). First, clinical evidence highlights the co-occurrence of distinct autoimmune diseases within an individual (that is, polyautoimmunity) and within members of a nuclear family (that is, familial autoimmunity). Second, physiopathologic evidence indicates that the pathologic mechanisms may be similar among autoimmune diseases. Lastly, genetic evidence shows that autoimmune phenotypes might represent pleiotropic outcomes of the interaction of non-specific disease genes.

  9. Dominant inhibition of Fas ligand-mediated apoptosis due to a heterozygous mutation associated with autoimmune lymphoproliferative syndrome (ALPS Type Ib

    Directory of Open Access Journals (Sweden)

    McDonald Jay M

    2007-07-01

    Full Text Available Abstract Background: Autoimmune lymphoproliferative syndrome (ALPS is a disorder of lymphocyte homeostasis and immunological tolerance due primarily to genetic defects in Fas (CD95/APO-1; TNFRSF6, a cell surface receptor that regulates apoptosis and its signaling apparatus. Methods: Fas ligand gene mutations from ALPS patients were identified through cDNA and genomic DNA sequencing. Molecular and biochemical assessment of these mutant Fas ligand proteins were carried out by expressing the mutant FasL cDNA in mammalian cells and analysis its effects on Fas-mediated programmed cell death. Results: We found an ALPS patient that harbored a heterozygous A530G mutation in the FasL gene that replaced Arg with Gly at position 156 in the protein's extracellular Fas-binding region. This produced a dominant-interfering FasL protein that bound to the wild-type FasL protein and prevented it from effectively inducing apoptosis. Conclusion: Our data explain how a naturally occurring heterozygous human FasL mutation can dominantly interfere with normal FasL apoptotic function and lead to an ALPS phenotype, designated Type Ib.

  10. The multiple autoimmune syndromes. A clue for the autoimmune tautology.

    Science.gov (United States)

    Anaya, Juan-Manuel; Castiblanco, John; Rojas-Villarraga, Adriana; Pineda-Tamayo, Ricardo; Levy, Roger A; Gómez-Puerta, José; Dias, Carlos; Mantilla, Ruben D; Gallo, Juan Esteban; Cervera, Ricard; Shoenfeld, Yehuda; Arcos-Burgos, Mauricio

    2012-12-01

    The multiple autoimmune syndromes (MAS) consist on the presence of three or more well-defined autoimmune diseases (ADs) in a single patient. The aim of this study was to analyze the clinical and genetic characteristics of a large series of patients with MAS. A cluster analysis and familial aggregation analysis of ADs was performed in 84 patients. A genome-wide microsatellite screen was performed in MAS families, and associated loci were investigated through the pedigree disequilibrium test. Systemic lupus erythematosus (SLE), autoimmune thyroid disease (AITD), and Sjögren's syndrome together were the most frequent ADs encountered. Three main clusters were established. Aggregation for type 1 diabetes, AITD, SLE, and all ADs as a trait was found. Eight loci associated with MAS were observed harboring autoimmunity genes. The MAS represent the best example of polyautoimmunity as well as the effect of a single genotype on diverse phenotypes. Its study provides important clues to elucidate the common mechanisms of ADs (i.e., autoimmune tautology).

  11. Diagnosis and classification of autoimmune gastritis.

    Science.gov (United States)

    Toh, Ban-Hock

    2014-01-01

    Autoimmune gastritis is a silent and highly prevalent disease that only becomes clinically manifested with progression to corpus atrophy and development of iron deficient or B12-deficient (pernicious) anaemia. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus. Corpus atrophy may be complicated by gastric carcinoids and gastric cancer. Laboratory diagnosis of autoimmune gastritis rests on serum biomarkers of antibody to parietal cell H/K ATPase and intrinsic factor and corpus atrophy on serum biomarkers of gastrin and pepsinogen levels. Subjects with asymptomatic parietal cell antibody should be regularly assessed for serum biomarkers for progression to corpus atrophy, development of iron and B12 deficiency anaemia and for associated autoimmune thyroiditis and type 1 diabetes mellitus.

  12. Beneficial autoimmunity at body surfaces– immune surveillance and rapid type 2 immunity regulate tissue homeostasis and cancer

    Directory of Open Access Journals (Sweden)

    Tim eDalessandri

    2014-07-01

    Full Text Available Epithelial cells line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation or toxins cause activation of epithelial cells with release of cytokines and chemokines as well as alterations in the expression of cell surface ligands. Such display of epithelial stress is rapidly sensed by tissue resident immunocytes, which can directly interact with self-moieties on epithelial cells and initiate both local and systemic immune responses. Epithelial cells are thus key drivers of immune surveillance at body surface tissues. However, epithelial cells have a propensity to drive type 2 immunity (rather than type 1 upon non-invasive challenge or stress – a type of immunity whose regulation and function still remain enigmatic. Here we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis.

  13. Polyglandular Autoimmune Syndrome in pregnancy: case report

    Science.gov (United States)

    Pecorino, Basilio; Teodoro, Maria Cristina; Scollo, Paolo

    2016-01-01

    Type III Polyglandular Autoimmune Syndrome is a multiple endocrine disorders disease determined by autoimmunity; it can be diagnosed if a patient is affected by Type 1 Diabetes Mellitus and another autoimmune disease, except Addison Disease, for example Autoimmune Hashimoto Thyroiditis or Celiac Disease. R.D., 34-year-old woman (gravida 2 para 1), was referred to the High Risk Pregnancy Outpatient Clinic at Cannizzaro Hospital in Catania at 8 weeks' gestation. She was affected from type III Polyglandular Autoimmune Disease (Type 1 Diabetes Mellitus, Autoimmune Hashimoto Thyroiditis and Celiac Disease). Pre-conception glycated hemoglobin and thyrotropin levels were normal. This pregnancy was characterized by glycemic instability and the need to increase the insulin units every month. The patient was hospitalized at 32+6 weeks for monitoring fetus and mother health because of inadequate glycemic control and the high insulin dosage required. She was delivered by caesarean section at 36+6 weeks because of uterine contractions, the previous cesarean section, glycemic instability and the gestational age. She delivered a baby boy, birth-weight 3300 g, Apgar 8-9. She was discharged in the fourth day after delivery with good maternal and child prognosis. Literature data and the experience derived by this case report suggest some recommendations to improve obstetrics and neonatologist outcome in the patients affected from type III Polyglandular Autoimmune Syndrome: pre-conception counseling, thyrotropin assay every 4-6 weeks, gluten-free diet, fasting and post-prandial blood glucose level targets. PMID:27917035

  14. Perspectives on autoimmunity

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, I.R.

    1987-01-01

    The contents of this book are: HLA and Autoimmunity; Self-Recognition and Symmetry in the Immune System; Immunology of Insulin Dependent Diabetes Mellitus; Multiple Sclerosis; Autoimmunity and Immune Pathological Aspects of Virus Disease; Analyses of the Idiotypes and Ligand Binding Characteristics of Human Monoclonal Autoantibodies to DNA: Do We Understand Better Systemic Lupus Erythematosus. Autoimmunity and Rheumatic Fever; Autoimmune Arthritis Induced by Immunization to Mycobacterial Antigens; and The Interaction Between Genetic Factors and Micro-Organisms in Ankylosing Spondylitis: Facts and Fiction.

  15. Type 1 Autoimmune Pancreatitis Can Transform into Chronic Pancreatitis: A Long-Term Follow-Up Study of 73 Japanese Patients

    Directory of Open Access Journals (Sweden)

    Masahiro Maruyama

    2013-01-01

    Full Text Available Some patients with autoimmune pancreatitis (AIP form pancreatic stones suggestive of transformation into chronic pancreatitis (CP. The present study examined the underlying risk factors and mechanism of AIP progression to confirmed CP. We compared the clinical and laboratory parameters of subjects who progressed to confirmed CP with those of the subjucts who did not in a cohort of 73 type 1 AIP patients. A total of 16 (22% AIP patients progressed to CP. Univariate analysis revealed that relapse was significantly more frequent in the progression group, and multivariate analysis indicated that pancreatic head swelling (OR 12.7, P=0.023 and nonnarrowing of the main pancreatic duct in the pancreatic body (OR 12.6, P=0.001 were significant independent risk factors for progression to CP. Kaplan-Meier testing showed that the progression rate to CP was approximately 10% at 3 years and 30% at 10 years in total AIP patients and 30% at 3 years and 60% at 10 years in subjects with both risk factors. AIP with pancreatic head swelling and a history of relapse may cause pancreatic juice stagnation and nonnarrowing of the main pancreatic duct in the pancreatic body, which can progress to advanced stage chronic pancreatitis.

  16. Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Liebman, Howard A; Weitz, Ilene C

    2017-03-01

    Autoimmune hemolytic anemia is an acquired autoimmune disorder resulting in the production of antibodies directed against red blood cell antigens causing shortened erythrocyte survival. The disorders can present as a primary disorder (idiopathic) or secondary to other autoimmune disorders, malignancies, or infections. Treatment involves immune modulation with corticosteroids and other agents.

  17. Histological Features and Biocompatibility of Bone and Soft Tissue Substitutes in the Atrophic Alveolar Ridge Reconstruction

    Directory of Open Access Journals (Sweden)

    Carlo Maiorana

    2016-01-01

    Full Text Available The reconstruction of the atrophic alveolar ridges for implant placement is today a common procedure in dentistry daily practice. The surgical reconstruction provides for the optimization of the supporting bone for the implants and a restoration of the amount of keratinized gingiva for esthetic and functional reasons. In the past, tissue regeneration has been performed with autogenous bone and free gingival or connective tissue grafts. Nowadays, bone substitutes and specific collagen matrix allow for a complete restoration of the atrophic ridge without invasive harvesting procedures. A maxillary reconstruction of an atrophic ridge by means of tissue substitutes and its histological features are then presented.

  18. Protective Action of Acupuncture and Moxibustion on Gastric Mucosa in Model Rats with Chronic Atrophic Gastritis

    Institute of Scientific and Technical Information of China (English)

    高希言; 饶红; 王燕; 孟丹; 魏玉龙

    2005-01-01

    Objective: To probe the mechanism of acupuncture and moxibustion in atrophic gastritis so as to provide a basis for clinical treatment. Method: Observe the effects of acupuncture and moxibustion at the points of Zusanli, Zhongwan and Tianshu on gastric mucosa in model rats with chronic atrophic gastritis. Results:Acupuncture and moxibustion can increase the contents of PGE2α, PGF2α and cAMP, and decrease the content of cGMP in the tissue of gastric mucosa. Conclusion: Acupuncture and moxibustion shows cytoprotection on gastric mucosa, so it is an effective method for treating chronic atrophic gastritis.

  19. Autoimmune Diseases

    Science.gov (United States)

    ... and the ends of the fingers and toes. Back pain can occur if the spine is involved. Rheumatoid ... for people with long-lasting muscle and joint pain. Some types of yoga or tai chi exercises may be helpful. Get ...

  20. Shaking Out Clues to Autoimmune Disease

    Science.gov (United States)

    ... susceptible people. Immune cells called T helper 17 (Th17) cells help us fight infection, but they’ve also been linked with several autoimmune disorders. Th17 cells, along with other types of helper T ...

  1. [Treatment with tacrolimus in autoimmune diseases].

    Science.gov (United States)

    Sádaba, B; Azanza, J R; García Quetglas, E; Fernández, V

    2004-01-01

    Tacrolimus is an immunosuppressive drug used most successfully as a primary drug to suppress the rejection of transplants. Tacrolimus may also be useful as a novel therapy for autoimmune disease. There are various reports in the bibliography about the use of tacrolimus in the treatment of some autoimmune diseases: inflammatory bowel disease, autoimmune hepatitis, cutaneous, neurologic, renal, endocrine or eye disease. In this review of more than 130 papers, we discuss the rationale for the use of tacrolimus in autoimmune disease and report the clinical experience with the drug in the management of a variety of autoimmune diseases. But, although there are a lot questions that require future research (dose, duration of treatment, when to begin tacrolimus treatment, how to monitor it, etc.), there is also wide experience with tacrolimus in the treatment of this type of disease.

  2. How pregnancy can affect autoimmune diseases progression?

    Science.gov (United States)

    Piccinni, Marie-Pierre; Lombardelli, Letizia; Logiodice, Federica; Kullolli, Ornela; Parronchi, Paola; Romagnani, Sergio

    2016-01-01

    Autoimmune disorders are characterized by tissue damage, caused by self-reactivity of different effectors mechanisms of the immune system, namely antibodies and T cells. Their occurrence may be associated with genetic and/or environmental predisposition and to some extent, have implications for fertility and obstetrics. The relationship between autoimmunity and reproduction is bidirectional. This review only addresses the impact of pregnancy on autoimmune diseases and not the influence of autoimmunity on pregnancy development. Th17/Th1-type cells are aggressive and pathogenic in many autoimmune disorders and inflammatory diseases. The immunology of pregnancy underlies the role of Th2-type cytokines to maintain the tolerance of the mother towards the fetal semi-allograft. Non-specific factors, including hormonal changes, favor a switch to Th2-type cytokine profile. In pregnancy Th2, Th17/Th2 and Treg cells accumulate in the decidua but may also be present in the mother's circulation and can regulate autoimmune responses influencing the progression of autoimmune diseases.

  3. Early manifestations of gastric autoimmunity in patients with juvenile autoimmune thyroid diseases.

    Science.gov (United States)

    Segni, Maria; Borrelli, Osvaldo; Pucarelli, Ida; Delle Fave, Gianfranco; Pasquino, Anna Maria; Annibale, Bruno

    2004-10-01

    Juvenile patients affected with autoimmune thyroid disorders showed a 14-21% prevalence of parietal cell antibodies (PCA) reacting against the H+/K+-ATPase of the gastric parietal cells. PCA are the principal immunological markers of atrophic body gastritis (ABG).ABG is characterized by loss of oxyntic glands, achlorhydria, and hypergastrinemia. The aim of this study was to determine whether PCA positivity could be associated with biochemical and histological manifestations of gastric autoimmunity in juvenile patients with autoimmune thyroid disease (AITD). We studied 129 children (96 females and 33 males) with chronic lymphocytic thyroiditis (n = 115) or Graves' disease (n = 14). Mean age at diagnosis of AITD was 9.7 +/- 3.3 yr, and mean age at sampling was 12.3 +/- 3.7 yr. We determined PCA and Helicobacter pylori antibodies, gastrin, and pepsinogen I plasma levels. Gastroscopy with multiple biopsies was carried out in a subgroup of patients with PCA positivity. We found that 30% of children had detectable PCA. Hypergastrinemia was found in 45% of the PCA-positive children (range, 40-675 pg/ml) vs. 12% of PCA-negative children (range, 35-65 pg/ml; P < 0.001). Eighteen patients with PCA positivity underwent gastroscopy; eight of these children had normogastrinemia, which showed no signs of ABG, and 10 children had hypergastrinemia, of whom five had mild to severe ABG. Our study shows that autoimmune gastritis is an early event in juvenile AITD with detectable PCA. Gastrin plasma level is a reliable marker of gastric atrophy.

  4. The Prevalence of Helicobacter pylori Infection Decreases with Older Age in Atrophic Gastritis

    Directory of Open Access Journals (Sweden)

    Shaohua Chen

    2013-01-01

    Full Text Available The clinical pathological characteristics of 3969 adult patients with chronic atrophic gastritis were retrospectively studied. The positivity of intestinal metaplasia and dysplasia in atrophic gastric specimens increased with age; however, H. pylori positivity and inflammatory activity decreased significantly with increased age. H. pylori infection was present in 21.01% of chronic atrophic gastritis patients, and 92.33% of the subjects with H. pylori infection were found to have simultaneous inflammatory activity. The intestinal metaplasia and dysplasia positivity markedly increased as the degree of gastric atrophy increased. In conclusion, the incidence of H. pylori infection decreased with age and correlated significantly with inflammatory activity in atrophic gastritis patients. The intestinal metaplasia and dysplasia positivity notably increased as the degree of gastric atrophy increased. Large population-based prospective studies are needed to better understand the progression of CAG.

  5. CASE OF REACTIVE PANCREATITIS IN PATIENTS WITH CHRONIC NON-ATROPHIC GASTRITIS FOLLOWING SEXUAL INTERCOURSE

    OpenAIRE

    Avramenko, A. A.

    2017-01-01

    It was analyzed the case of reactive pancreatitis in patients with chronic non-atrophic gastritis, which passed a comprehensive examination and planned to undergo a course of treatment. It was found that reactive pancreatitis developed after sexual intercourse.

  6. Development of turbinate lesions and nasal colonization by Bordetella bronchiseptica and Pasteurella multocida during long-term exposure of healthy pigs to pigs affected by atrophic rhinitis.

    OpenAIRE

    Bäckström, L R; Brim, T A; Collins, M T

    1988-01-01

    Natural transmission of atrophic rhinitis from pigs from a herd with an endemic atrophic rhinitis problem to pigs from a herd free of atrophic rhinitis was demonstrated. Six replicates each with five pigs from the endemic atrophic rhinitis herd (Group A) and five pigs from the atrophic rhinitis-free herd (Group B) were housed together from 5 wk of age, with each replicate kept in isolation rooms maintained at optimal and controlled environmental conditions. Three replicates each with six pigs...

  7. Modified ridge splitting technique using conical space maintainers for delayed implant placement in highly atrophic maxillae.

    OpenAIRE

    Cabanes Gumbau, Guillermo; Silvestre Donat, Francisco Javier

    2010-01-01

    Background: A low-morbidity surgical technique is described for the horizontal augmentation of highly atrophic alveolar ridges in which first surgical step implant placement is contraindicated. The aim of this case report was to present an alternative treatment for the rehabilitation of the atrophic maxilla. Methods: The technique involves a crestal corticotomy with transverse expansion of the vestibular and lingual cortical layers, followed by the placement of threaded titaniu...

  8. Aetiopathogenesis of autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Diego Vergani; Giorgina Mieli-Vergani

    2008-01-01

    in the presence of TGF-β,but in the absence of IL-6.If regulatory mechanisms fail,the autoimmune attack is perpetuated.Over the past three decades different aspects of the above pathogenic scenario have been investigated.In particular,a defect in immunoregulation affecting CD4+CD25+regulatory T cells (T-regs) has been demonstrated in AIH,particularly at diagnosis or during relapse.Advances in the study of autoreactive T cells have occurred mostly in AIH type 2,since the knowledge that CYP2D6 is the main autoantigen has enabled the characterization of both CD4 and CD8 T cells targeting this cytochrome.CD4 T cells from patients with type 2 AIH positive for the predisposing HLA allele DRB1*0701 recognize seven regions of CYP2D6,five of which are also recognized by CD8 T cells.High numbers of IFN-γ producing CD4 T cells and CD8 T cells are associated with biochemical evidence of liver damage,suggesting a combined cellular immune attack.

  9. Autoimmune pancreatitis associated with primary sclerosing cholangitis: MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Eerens, I.; Vanbeckevoort, D.; Van Hoe, L. [University Hospital, Leuven (Belgium). Dept. of Radiology; Vansteenbergen, W. [Dept. of Hepatology, University Hospitals KU, Leuven (Belgium)

    2001-08-01

    Autoimmune pancreatitis is a relatively rare type of chronic pancreatitis that may be associated with other autoimmune disorders. The imaging features of this entity may be misleading and suggest the presence of a malignant tumour. We present a case in which MR imaging allowed us to diagnose autoimmune pancreatitis associated with primary sclerosing cholangitis, which is another autoimmune-related disease. Typical MR characteristics of autoimmune pancreatitis include focal or diffuse enlargement of the pancreas, the absence of parenchymal atrophy and significant dilation proximal to the site of stenosis, the absence of peripancreatic spread, the clear demarcation of the lesion and the presence of a peripancreatic rim. (orig.)

  10. Sirolimus for Autoimmune Disease of Blood Cells

    Science.gov (United States)

    2017-03-16

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  11. Autoimmune cholangitis mimicking a klatskin tumor: a case report

    Directory of Open Access Journals (Sweden)

    Zwirewich Charles

    2011-09-01

    Full Text Available Abstract Introduction Autoimmune cholangitis remains an elusive manifestation of immunoglobulin G4-associated systemic disease most commonly encountered in patients with autoimmune pancreatitis. No strict diagnostic criteria have been described to date and diagnosis mainly relies on a combination of clinical and histopathologic findings. It is hence even more challenging to diagnose autoimmune cholangitis in patients with late or atypical presentations, such as without concomitant pancreatic involvement. Early diagnosis of this rare disorder can significantly improve outcomes considering high rates of surgical intervention, as well as high relapse rates in the absence of steroid treatment. To the best of our knowledge the literature is quite sparse on cases with atypical presentations of autoimmune cholangitis. Case presentation We report a case of a previously healthy 65-year-old man of Middle-Eastern origin, with a history of pancreatic insufficiency of unknown etiology, evaluated for elevated liver function tests found incidentally on a routine physical examination. Imaging studies revealed an atrophic pancreas and biliary duct dilatation consistent with obstruction. Subsequent endoscopic retrograde cholangiopancreatography showed a bile duct narrowing pattern suggestive of cholangiocarcinoma, but brushings failed to reveal malignant cells. Our patient proceeded to undergo surgical resection. Histological examination of the resected mass revealed lymphoplasmacytic infiltrate with no malignant features. Our patient returned three months later with persistently high liver function tests and no evidence of biliary obstruction on imaging. A presumptive diagnosis of autoimmune cholangitis was made and our patient's symptoms resolved after a short course of an oral steroid regimen. Post factum staining of the resection specimen revealed an immunoglobulin G4 antibody positive immune cell infiltrate, consistent with the proposed diagnosis. Conclusion

  12. The Diagnostic Value of Gastrin-17 Detection in Atrophic Gastritis

    Science.gov (United States)

    Wang, Xu; Ling, Li; Li, Shanshan; Qin, Guiping; Cui, Wei; Li, Xiang; Ni, Hong

    2016-01-01

    Abstract A meta-analysis was performed to assess the diagnostic value of gastrin-17 (G-17) for the early detection of chronic atrophic gastritis (CAG). An extensive literature search was performed, with the aim of selecting publications that reported the accuracy of G-17 in predicting CAG, in the following databases: PubMed, Science Direct, Web of Science, Chinese Biological Medicine, Chinese National Knowledge Infrastructure, Wanfang, and VIP. To assess the diagnostic value of G-17, the following statistics were estimated and described: sensitivity, specificity, diagnostic odds ratios (DOR), summary receiver operating characteristic curves, area under the curve (AUC), and 95% confidence intervals (CIs). Thirteen studies that met the inclusion criteria were included in this meta-analysis, comprising 894 patients and 1950 controls. The pooled sensitivity and specificity of these studies were 0.48 (95% CI: 0.45–0.51) and 0.79 (95% CI: 0.77–0.81), respectively. The DOR was 5.93 (95% CI: 2.93–11.99), and the AUC was 0.82. G-17 may have potential diagnostic value because it has good specificity and a moderate DOR and AUC for CAG. However, more studies are needed to improve the sensitivity of this diagnostic tool in the future. PMID:27149493

  13. Galectin-3 in autoimmunity and autoimmune diseases.

    Science.gov (United States)

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

    2015-08-01

    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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...

  15. An unusual case of atrophic mandible fracture in a patient with osteogenesis imperfecta and on oral bisphosphonate therapy: Case report

    Directory of Open Access Journals (Sweden)

    Abdulrahman Al-Osaimi

    2014-04-01

    Full Text Available Fractures of severely atrophic (height < 10 mm edentulous mandibles are infrequent and challenging to manage. Factors such as sclerotic bone and decreased vascularity combined with systemic diseases complicate the management of such fractures. Osteogenesis imperfecta (OI is a heterogeneous group of inherited disorders of type I collagen metabolism. Patients with OI characteristically present with histories of long bone fractures, deformities, blue sclerae, and opalescent dentin. However, fractures of the facial skeleton are rare. Bisphosphonate therapy has been proven to effectively reduce the fracture risk in patients with OI. The purpose of this clinical report is to present an unusual case of spontaneous fracture of the atrophic mandible in a patient with OI. Despite open reduction and internal fixation (ORIF with miniplate osteosynthesis, the patient developed a second fracture at a screw placement site distal to the first fracture. The patient was successfully treated with ORIF using locking reconstruction plates fixed in the symphyseal and angle regions. Bone healing following ORIF was normal, and no clinical sign of osteonecrosis as a result of bisphosphonate therapy was observed. Patients with OI can present with spontaneous fractures of already weakened mandibles. Although such fractures can be managed with care using established protocols, further research is required to examine the effects of concomitant medication, such as bisphosphonates.

  16. Simultaneous sinus lifting and alveolar distraction of a severely atrophic posterior maxilla for oral rehabilitation with dental implants.

    Science.gov (United States)

    Kanno, Takahiro; Mitsugi, Masaharu; Paeng, Jun-Young; Sukegawa, Shintaro; Furuki, Yoshihiko; Ohwada, Hiroyuki; Nariai, Yoshiki; Ishibashi, Hiroaki; Katsuyama, Hideaki; Sekine, Joji

    2012-01-01

    We retrospectively reviewed a new preimplantation regenerative augmentation technique for a severely atrophic posterior maxilla using sinus lifting with simultaneous alveolar distraction, together with long-term oral rehabilitation with implants. We also analyzed the regenerated bone histomorphologically. This study included 25 maxillary sinus sites in 17 patients. The technique consisted of alveolar osteotomy combined with simultaneous sinus lifting. After sufficient sinus lifting, a track-type vertical alveolar distractor was placed. Following a latent period, patient self-distraction was started. After the required augmentation was achieved, the distractor was left in place to allow consolidation. The distractor was then removed, and osseointegrated implants (average of 3.2 implants per sinus site, 80 implants) were placed. Bone for histomorphometric analysis was sampled from six patients and compared with samples collected after sinus lifting alone as controls (n = 4). A sufficient alveolus was regenerated, and all patients achieved stable oral rehabilitation. The implant survival rate was 96.3% (77/80) after an average postloading followup of 47.5 months. Good bone regeneration was observed in a morphological study, with no significant difference in the rate of bone formation compared with control samples. This new regenerative technique could be a useful option for a severely atrophic maxilla requiring implant rehabilitation.

  17. Simultaneous Sinus Lifting and Alveolar Distraction of a Severely Atrophic Posterior Maxilla for Oral Rehabilitation with Dental Implants

    Directory of Open Access Journals (Sweden)

    Takahiro Kanno

    2012-01-01

    Full Text Available We retrospectively reviewed a new preimplantation regenerative augmentation technique for a severely atrophic posterior maxilla using sinus lifting with simultaneous alveolar distraction, together with long-term oral rehabilitation with implants. We also analyzed the regenerated bone histomorphologically. This study included 25 maxillary sinus sites in 17 patients. The technique consisted of alveolar osteotomy combined with simultaneous sinus lifting. After sufficient sinus lifting, a track-type vertical alveolar distractor was placed. Following a latent period, patient self-distraction was started. After the required augmentation was achieved, the distractor was left in place to allow consolidation. The distractor was then removed, and osseointegrated implants (average of 3.2 implants per sinus site, 80 implants were placed. Bone for histomorphometric analysis was sampled from six patients and compared with samples collected after sinus lifting alone as controls (n=4. A sufficient alveolus was regenerated, and all patients achieved stable oral rehabilitation. The implant survival rate was 96.3% (77/80 after an average postloading followup of 47.5 months. Good bone regeneration was observed in a morphological study, with no significant difference in the rate of bone formation compared with control samples. This new regenerative technique could be a useful option for a severely atrophic maxilla requiring implant rehabilitation.

  18. Autoimmune hepatitis: what must be said.

    Science.gov (United States)

    Mackay, Ian R

    2012-12-01

    Autoimmune hepatitis (AIH) was first studied under its earlier name of "chronic active hepatitis" (CAH) from the 1950s, coincident with a renaissance of interest in autoimmunity. The definition of autoimmune serum reactants in disease, including CAH, gave new insights into chronic hepatitis and liver cirrhosis, and led to refinements of Burnet's clonal selection theory of acquired immunity, 1957-59. Various discoveries including serological reactants in CAH prompted its designation in 1965 as autoimmune hepatitis, and treatment with immunosuppressive drug regimens transformed outcomes and survival. Serological observations further indicated that AIH could exist as either of two types, clinically similar but genetically different: Type 1 aligned more with the non-organ-specific multisystem diseases, and the infrequent Type 2 more with the organ-specific diseases. However, events in either type that could explain the onset of autoimmunity in the normally tolerogenic milieu of the liver have not been discerned. In the genetically predisposed individual, initiation may depend on non-specific death of hepatocytes after which fragments derived from disordered apoptosis acquire the capacity for ongoing auto-immunogenic stimulation. Insufficiency in numbers and function of Treg populations appears important in the promotion of this autoimmune process.

  19. Autoimmune pancreatitis: A review

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the proposed diagnostic criteria and treatment algorithms.

  20. Dilemmas in autoimmune pancreatitis. Surgical resection or not?

    Science.gov (United States)

    Hoffmanova, I; Gurlich, R; Janik, V; Szabo, A; Vernerova, Z

    Surgical treatment is not commonly recommended in the management of autoimmune pancreatitis. The article describes a dilemma in diagnostics and treatment of a 68-year old man with the mass in the head of the pancreas that mimicked pancreatic cancer and that was diagnosed as a type 1 autoimmune pancreatitis (IgG4-related pancreatitis) after a surgical resection. Diagnosis of the autoimmune pancreatitis is a real clinical challenge, as in the current diagnostic criteria exists some degree of overlap in the findings between autoimmune pancreatitis and pancreatic cancer (indicated by the similarity in radiologic findings, elevation of IgG4, sampling errors in pancreatic biopsy, and the possibility of synchronous autoimmune pancreatitis and pancreatic cancer). Despite the generally accepted corticosteroids as the primary treatment modality in autoimmune pancreatitis, we believe that surgical resection remains necessary in a specific subgroup of patients with autoimmune pancreatitis (Fig. 4, Ref. 37).

  1. Humanized in vivo Model for Autoimmune Diabetes

    Science.gov (United States)

    2009-02-01

    AWARD NUMBER: W81XWH-07-1-0121 TITLE: Humanized in vivo Model for Autoimmune Diabetes PRINCIPAL INVESTIGATOR: Gerald T Nepom, M.D., Ph.D...4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Humanized in vivo Model for Autoimmune Diabetes Sb. GRANT NUMBER W81XWH-07-1-0121 Sc. PROGRAM ELEMENT...therapies. This research study entails using humanized mice manifesting type 1 diabetes (T1 D)-associated human HLA molecules to address the fate and

  2. Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity

    NARCIS (Netherlands)

    Hrdlickova, Barbara; Kumar, Vinod; Kanduri, Kartiek; Zhernakova, Daria V.; Tripathi, Subhash; Karjalainen, Juha; Lund, Riikka J.; Li, Yang; Ullah, Ubaid; Modderman, Rutger; Abdulahad, Wayel; Lahdesmaki, Harri; Franke, Lude; Lahesmaa, Riitta; Wijmenga, Cisca; Withoff, Sebo

    2014-01-01

    Background: Although genome-wide association studies (GWAS) have identified hundreds of variants associated with a risk for autoimmune and immune-related disorders (AID), our understanding of the disease mechanisms is still limited. In particular, more than 90% of the risk variants lie in non-coding

  3. Atrophic and Metaplastic Progression in the Background Mucosa of Patients with Gastric Adenoma

    Science.gov (United States)

    Bae, Suh Eun; Lee, Jeong Hoon; Park, Young Soo; Ahn, Ji Yong; Kim, Do Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Jang, Se Jin; Jung, Hwoon-Yong

    2017-01-01

    Background In patients with adenoma, assessing premalignant changes in the surrounding mucosa is important for surveillance. This study evaluated atrophic and metaplastic progression in the background mucosa of adenoma or early gastric cancer (EGC) cases. Methods Among 146 consecutive patients who underwent endoscopic resection for intestinal-type gastric neoplasia, the adenoma group included 56 patients with low-grade dysplasia and the ECG group included 90 patients with high-grade dysplasia or invasive carcinoma. For histology, 3 paired biopsies were obtained from the antrum, corpus lesser curvature (CLC), and corpus greater curvature (CGC). Serological atrophy was determined based on pepsinogen A (PGA), progastricsin (PGC), gastrin-17, and total ghrelin levels. Topographic progression of atrophy and/or metaplasia was staged using the operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia assessment (OLGIM) systems. Results Rates of moderate-to-marked histological atrophy/metaplasia in patients with adenoma were 52.7%/78.2% at the antrum (vs. 58.8%/76.4% in EGC group), 63.5%/75.0% at the CLC (vs. 60.2%/69.7% in EGC group), and 10.9%/17.9% at the CGC (vs. 5.6%/7.8% in EGC group). Serological atrophy indicated by PGA and PGC occurred in 23.2% and 15.6% of cases in the adenoma and ECG groups, respectively (p = 0.25). Mean serum gastrin-17 concentrations of the adenoma group and EGC group were 10.4 and 9.0 pmol/L, respectively (p = 0.54). Mean serum total ghrelin levels were 216.6 and 209.5 pg/mL, respectively (p = 0.71). Additionally, between group rates of stage III–IV OLGA and OLGIM were similar (25.9% vs. 25.0%, p = 0.90; 41.8% vs. 44.9%, p = 0.71, respectively). Conclusions Atrophic and metaplastic progression is extensive and severe in gastric adenoma patients. A surveillance strategy for metachronous tumors should be applied similarly for patients with adenoma or EGC. PMID:28072871

  4. Ablative non-fractional lasers for atrophic facial acne scars: a new modality of erbium:YAG laser resurfacing in Asians.

    Science.gov (United States)

    Lee, Sang Ju; Kang, Jin Moon; Chung, Won Soon; Kim, Young Koo; Kim, Hei Sung

    2014-03-01

    Atrophic facial scars which commonly occur after inflammatory acne vulgaris can be extremely disturbing to patients both physically and psychologically. Treatment with fractional laser devices has become increasingly popular, but there has been disappointment in terms of effectiveness. The objective of this study was to assess the safety and efficacy of ablative full-face resurfacing on atrophic acne scars in the Korean population. A total of 22 patients, aged 25-44 years, underwent a new modality of resurfacing combining both short-pulsed and dual-mode erbium:yttrium-aluminum garnet (Er:YAG) laser. The patients had Fitzpatrick skin types ranging from III to V. Photographs were taken before and up to 6 months after treatment. Results were evaluated for the degree of clinical improvement and any adverse events. Degree of improvement was graded using a four-point scale: poor (1) = 75%. Based on the blinded photo assessments by two independent reviewers, clinically and statistically significant mean improvement of 3.41 was observed (one-sample Wilcoxon signed rank test, P laser resurfacing combining short-pulsed and dual-mode Er:YAG laser is a safe and very effective treatment modality for atrophic facial acne scars in Asians with darker skin tones.

  5. Atrophic dermatofibrosarcoma protuberans with the fusion gene COL1A1-PDGFB detected by RT-PCR using only a single primer pair.

    Science.gov (United States)

    Xu, Wen-Jun; Wang, Ju-Sheng

    2015-01-01

    Dermatofibrosarcoma protuberans (DFSPs) is an uncommon dermal tumor of intermediate to low-grade malignancy. A few patients have clinically persistent plaques that might be atrophic, and they are difficult to be diagnosed clinically. With the development of cytogenetic and molecular biology techniques, the detection of fusion transcripts of the collagen type 1a1 (COL1A1) and platelet-derived growth factor-BB (PDGFB) genes has been recognized as a reliable and valuable molecular tool for the diagnosis of DFSPs. We reported a 24-year-old woman who had a 2 years history of atrophic DFSPs, and detected the gene fusion between COL1A1 to PDGFB by one-step method of RT-PCR using only a single primer pair. The gene fusion detected by this rapid and efficient one-step method in our patient appears to be the first report of atrophic DFSPs, and we detected a novel COL1A1 breakpoint between exon 2 and exon 3.

  6. Malignant atrophic papulosis (Köhlmeier-Degos disease - A review

    Directory of Open Access Journals (Sweden)

    Theodoridis Athanasios

    2013-01-01

    Full Text Available Abstract Definition of the disease Malignant atrophic papulosis (MAP, described independently by Köhlmeier and Degos et al., is a rare, chronic, thrombo-obliterative vasculopathy characterized by papular skin lesions with central porcelain-white atrophy and surrounding teleangiectatic rim. Epidemiology Less than 200 cases have been described in the literature. The first manifestation of MAP usually occurs between the 20th and 50th year of life. Clinical description The cutaneous clinical picture is almost pathognomonic. The histology is not consistent but in most cases it shows a wedge-shaped connective tissue necrosis in the deep corium due to a thrombotic occlusion of the small arteries. In the systemic variant, manifestations mostly occur at the intestine and central nervous system. Etiology The etiopathogenesis of the disease remains unknown, a genetic predisposition may occur. Vasculitis, coagulopathy or primary dysfunction of the endothelial cells have been implicated. Diagnostic methods Diagnosis is only based on the characteristic skin lesions. Differrential diagnosis It depends on the clinical presentation of MAP, but systemic lupus erythematosus and other connective tissue diseases need to be considered. Management No effective treatment exists for the systemic manifestations, while compounds that facilitate blood perfusion have achieved a partial regression of the skin lesions in single cases. Prognosis An apparently idiopathic, monosymptomatic, cutaneous, benign variant and a progressive, visceral one with approx. 50% lethality within 2–3 years have been reported. Systemic manifestations can develop years after the occurrence of skin lesions leading to bowel perforation and peritonitis, thrombosis of the cerebral arteries or massive intracerebral hemorrhage, meningitis, encephalitis, radiculopathy, myelitis.

  7. Outcome of dermal grafting in the management of atrophic facial scars

    Directory of Open Access Journals (Sweden)

    Kanathur Shilpa

    2016-01-01

    Full Text Available Background: Scars over the face are cosmetically and psychologically disturbing. Various techniques have been described and are being practiced in the management of these scars. Aims and Objectives: This study was undertaken to study the safety, effectiveness of using dermal grafts as fillers in the management of facial scars due to acne, chickenpox, trauma or any others. Materials and Methods: Fifteen patients with atrophic facial scars of varied aetiology and willing for surgery were considered for dermal graft technique. After pre-operative workup, subcision was done 2 weeks before planned surgery. Depending on the type of scar, grafts were inserted using pocket or road railing techniques. Scar improvement was assessed based on patient satisfaction. Results: Linear scars showed excellent improvement. Acne, varicella and traumatic scars also showed good improvement. However, two patients did not appreciate improvement due to marked surface irregularities as the scars were elevated. They were further subjected to LASER and chemical peel resurfacing. Conclusion: Dermal grafting can be used in the management of any round to oval facial scar which is soft, prominent and at least 4-5 mm across; linear scars at least 2-3 mm across and 3-4 cm in length. However, scars with prominent surface irregularities need further resurfacing techniques along with dermal grafting. Limitations: Limitations of the study include small sample size, and only subjective assessment of the scar has been taken into consideration to assess the outcome.

  8. [Syndrome overlap: autoimmune hepatitis and autoimmune cholangitis].

    Science.gov (United States)

    Guerra Montero, Luis; Ortega Alvarez, Félix; Marquez Teves, Maguin; Asato Higa, Carmen; Sumire Umeres, Julia

    2016-01-01

    Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune cholangitis are chronic autoimmune liver disease, usually present separate, the cases where characteristics of two of the above is observed liver disease is commonly referred to as Overlap Syndromes (OS). Although there is no consensus on specific criteria for the diagnosis of OS identification of this association is important for initiating appropriate treatment and prevent its progression to cirrhosis or at least the complications of cirrhosis and death. We report the case of awoman aged 22 cirrhotic which debuted are edematous ascites, severe asthenia and jaundice compliant diagnostics SS criteria and initially present any response to treatment with ursodeoxycholic acid and oral corticosteroids, but ultimately finished performing a transplant orthotopic liver.

  9. THE AUTOIMMUNE ECOLOGY.

    Directory of Open Access Journals (Sweden)

    Juan-Manuel eAnaya

    2016-04-01

    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. Bistability in autoimmune diseases

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Mosekilde, Erik; Lund, Ole

    2011-01-01

    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...

  11. The Autoimmune Ecology.

    Science.gov (United States)

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

    2016-01-01

    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.

  12. Autoimmune polyendocrinopathy and hypophysitis after Puumala hantavirus infection

    Science.gov (United States)

    Tarvainen, Marlene; Mäkelä, Satu; Mustonen, Jukka

    2016-01-01

    Summary Puumala hantavirus (PUUV) infection causes nephropathia epidemica (NE), a relatively mild form of haemorrhagic fever with renal syndrome (HFRS). Hypophyseal haemorrhage and hypopituitarism have been described in case reports on patients with acute NE. Chronic hypopituitarism diagnosed months or years after the acute illness has also been reported, without any signs of a haemorrhagic aetiology. The mechanisms leading to the late-onset hormonal defects remain unknown. Here, we present a case of NE-associated autoimmune polyendocrinopathy and hypopituitarism presumably due to autoimmune hypophysitis. Thyroid peroxidase antibody seroconversion occurred between 6 and 12 months, and ovarian as well as glutamate decarboxylase antibodies were found 18 months after acute NE. Brain MRI revealed an atrophic adenohypophysis with a heterogeneous, low signal intensity compatible with a sequela of hypophysitis. The patient developed central (or mixed central and peripheral) hypothyroidism, hypogonadism and diabetes insipidus, all requiring hormonal replacement therapy. This case report suggests that late-onset hormonal defects after PUUV infection may develop by an autoimmune mechanism. This hypothesis needs to be confirmed by prospective studies with sufficient numbers of patients. Learning points: Pituitary haemorrhage resulting in hypopituitarism has been reported during acute HFRS caused by PUUV and other hantaviruses. Central and peripheral hormone deficiencies developing months or years after HFRS have also been found, with an incidence higher than that in the general population. The pathogenesis of these late-onset hormonal defects remains unknown. This case report suggests that the late-onset hypopituitarism and peripheral endocrine defects after HFRS could evolve via autoimmune mechanisms. The sensitivity of current anti-pituitary antibody (APA) tests is low. A characteristic clinical course, together with typical brain MRI and endocrine findings may be

  13. Comparative proteomics analysis of chronic atrophic gastritis: changes of protein expression in chronic atrophic gastritis with out Helicobacter pylori infection

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Lin; Hou, Yanhong; Wu, Kai; Li, Dan [Department of Gastroenterology and Hepatology, The 309 Hospital of People' s Liberation Army, Beijing (China)

    2012-03-02

    Chronic atrophic gastritis (CAG) is a very common gastritis and one of the major precursor lesions of gastric cancer, one of the most common cancers worldwide. The molecular mechanism underlying CAG is unclear, but its elucidation is essential for the prevention and early detection of gastric cancer and appropriate intervention. A combination of two-dimensional gel electrophoresis and mass spectrometry was used in the present study to analyze the differentially expressed proteins. Samples from 21 patients (9 females and 12 males; mean age: 61.8 years) were used. We identified 18 differentially expressed proteins in CAG compared with matched normal mucosa. Eight proteins were up-regulated and 10 down-regulated in CAG when compared with the same amounts of proteins in individually matched normal gastric mucosa. Two novel proteins, proteasome activator subunit 1 (PSME1), which was down-regulated in CAG, and ribosomal protein S12 (RPS12), which was up-regulated in CAG, were further investigated. Their expression was validated by Western blot and RT-PCR in 15 CAG samples matched with normal mucosa. The expression level of RPS12 was significantly higher in CAG than in matched normal gastric mucosa (P < 0.05). In contrast, the expression level of PSME1 in CAG was significantly lower than in matched normal gastric mucosa (P < 0.05). This study clearly demonstrated that there are some changes in protein expression between CAG and normal mucosa. In these changes, down-regulation of PSME1 and up-regulation of RPS12 could be involved in the development of CAG. Thus, the differentially expressed proteins might play important roles in CAG as functional molecules.

  14. Autoimmune polyendocrinopathy and hypophysitis after Puumala hantavirus infection

    Directory of Open Access Journals (Sweden)

    Marlene Tarvainen

    2016-11-01

    Full Text Available Puumala hantavirus (PUUV infection causes nephropathia epidemica (NE, a relatively mild form of haemorrhagic fever with renal syndrome (HFRS. Hypophyseal haemorrhage and hypopituitarism have been described in case reports on patients with acute NE. Chronic hypopituitarism diagnosed months or years after the acute illness has also been reported, without any signs of a haemorrhagic aetiology. The mechanisms leading to the late-onset hormonal defects remain unknown. Here, we present a case of NE-associated autoimmune polyendocrinopathy and hypopituitarism presumably due to autoimmune hypophysitis. Thyroid peroxidase antibody seroconversion occurred between 6 and 12 months, and ovarian as well as glutamate decarboxylase antibodies were found 18 months after acute NE. Brain MRI revealed an atrophic adenohypophysis with a heterogeneous, low signal intensity compatible with a sequela of hypophysitis. The patient developed central (or mixed central and peripheral hypothyroidism, hypogonadism and diabetes insipidus, all requiring hormonal replacement therapy. This case report suggests that late-onset hormonal defects after PUUV infection may develop by an autoimmune mechanism. This hypothesis needs to be confirmed by prospective studies with sufficient numbers of patients.

  15. Role of Complement in Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Berentsen, Sigbjørn

    2015-09-01

    The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed.

  16. Autoimmune liver disease in Noonan Syndrome.

    Science.gov (United States)

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

    2015-03-01

    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.

  17. Autoimmune Cholangitis: A Variant Syndrome of Autoimmune Hepatitis

    OpenAIRE

    Brij Sharma; Sujeet Raina; Rajesh Sharma

    2014-01-01

    Autoimmune cholangitis (AIC) or autoimmune cholangiopathy is a chronic inflammation of liver and a variant syndrome of autoimmune hepatitis (AIH). We present a case of an adult female who had biochemical features of cholestasis and transaminasemia but aminotransferases were not in the hepatitis range and had histological evidence of bile duct injury which was subsequently diagnosed as autoimmune cholangitis.

  18. Síndrome Poliglandular Autoinmune Tipo II: Posible Asociación con HLA DRB1*-DQB1* Possible association of Type II Autoimmune Polyendrocrine Syndrome with HLA DRB1*-DQB1*

    Directory of Open Access Journals (Sweden)

    M.S. Mallea Gil

    2010-12-01

    Full Text Available Los síndromes poliendocrinos autoinmunes (APS asocian enfermedades endocrinas autoinmunes con otros desórdenes autoinmunes no endocrinos. El APS tipo II se caracteriza por compromiso primario suprarrenal, tiroideo y/o DM tipo I. Presentamos un paciente masculino de 46 años que fue internado por astenia, adinamia, hiporexia, severa disminución de peso, mareos y vómitos. Antecedente de obesidad y diabetes diagnosticada 3 años antes. Presentaba hipotensión arterial, hiperpigmentación de mucosas y pliegues, anemia, hiponatremia e hipoglucemias frecuentes a pesar de la disminución de la dosis de insulina. Se diagnosticó insuficiencia suprarrenal, concomitantemente con hipotiroidismo y diabetes tipo 1, todas de origen autoinmune, iniciándose reemplazo hormonal. Se encontró una posible asociación del HLA DRB1*-DQB1* en los estudios genéticos. Conclusiones: Nuestro paciente presenta el HLA DQB1*0302 descripto en el APSII, pero el HLA DRB1 *08 encontrado no está descripto en este síndrome ni en ningún otro desorden autoinmune. En pacientes con Diabetes tipo 1 que disminuyan el requerimiento insulínico, habría que descartar insuficiencia suprarrenal, un componente del APS II, como factor etiológico, a pesar de su baja prevalencia.Autoimmune polyendocrine syndromes (APS are the association of autoimmune endocrine diseases with other non-endocrine autoimmune disorders. Type II APS is defined by occurrence of Addison´s disease with thyroid autoimmune disease and/or type 1 diabetes mellitus. We present a 46-year-old male patient who was hospitalized because of asthenia, adynamia, hyporexia, severe loss of weight, dizziness and vomiting. Diabetes mellitus had been diagnosed 3 years earlier when he was obese. He presented arterial hypotension, anemia, darkening of the skin and oral mucosa, hyponatremia and frequent hypoglycemia although his insulin dose was decreased. Adrenal insufficiency was diagnosed together with hypothyroidism and type

  19. Psoriasis and autoimmunity.

    Science.gov (United States)

    Sticherling, Michael

    2016-12-01

    Psoriasis is one of the most common chronic inflammatory human skin diseases. Though clinically well characterized, the exact etiological and pathogenic mechanisms are still not known in detail. Current knowledge indicates distinct overlap to other inflammatory as well as autoimmune disorders. However, the one or more relevant autoantigens could not be characterized so-far. On the other side, several autoimmune diseases were shown to be associated with psoriasis. In addition, serological autoimmune phenomena, namely diverse circulating specific autoantibodies could be demonstrated in the past. A matter of current debate is if psoriasis is a primary autoimmune disease or secondarily evolving into autoimmunity as seen in other chronic inflammatory diseases. Related to this aspect is the concept of autoinflammation versus autoimmunity where psoriasis shares mechanisms of both entities. Though T-cells remain among the most important cellular players in the pathogenesis of psoriasis and current therapeutic strategies successfully target these cells or their products irrespective of these concepts, autoimmunity if relevant will add to the treatment armamentarium by using protective and prophylactic antigen-specific modalities.

  20. [Narcolepsy as an autoimmune disease].

    Science.gov (United States)

    Sarkanen, Tomi; Vaarala, Outi; Julkunen, Ilkka; Partinen, Markku

    2015-01-01

    Narcolepsy is a sleep disorder of central origin. Hypocretin deficiency is the essential feature of type 1 narcolepsy. The biological background of type 2 narcolepsy (without cataplexy) is less clear. Infections or other external factors are thought to function as triggers of narcolepsy. After the H1N1 vaccination campaign, the incidence of narcolepsy increased clearly in countries where a vaccine boosted with the AS03 adjuvant was used. According to the current view, the increase of narcolepsy in connection with the pandemic vaccine especially in children and adolescents was associated with the virus component of the vaccine, but the adjuvant may also have boosted the development of autoimmune response.

  1. Promoter polymorphisms in trefoil factor 2 and trefoil factor 3 genes and susceptibility to gastric cancer and atrophic gastritis among Chinese population.

    Science.gov (United States)

    Xu, Qian; Chen, Mo-Ye; He, Cai-Yun; Sun, Li-Ping; Yuan, Yuan

    2013-10-15

    The polymorphisms in trefoil factor (TFF) gene family that protect gastrointestinal epithelium might influence individual vulnerability to gastric cancer (GC) and atrophic gastritis. We used the Sequenom MassARRAY platform to identify the genotypes of TFF2 rs3814896 and TFF3 rs9981660 polymorphisms in 478 GC patients, 652 atrophic gastritis patients, and 724 controls. For the TFF2 rs3814896 polymorphism, in the subgroup aged ≤ 50 years, we found that AG+GG genotypes were associated with a 0.746-fold decreased risk of atrophic gastritis [p=0.023, 95% confidence interval (CI)=0.580-0.960], a 0.626-fold decreased risk of GC (p=0.005, 95% CI=0.451-0.868), and a 0.663-fold decreased risk of diffuse-type GC (p=0.034, 95% CI=0.452-0.970) compared with the common AA genotype. For the TFF3 rs9981660 polymorphism, in the male subgroup, individuals with variant AG+AA genotype were associated with a 0.761-fold decreased risk of diffuse-type GC compared with the common GG genotype (p=0.043, 95% CI=0.584-0.992). Additionally, we found that in subjects aged ≤ 50 years compared with common AA genotype, TFF2 rs3814896 AG+GG genotypes were associated with increased TFF2 mRNA levels in the total gastric cancer specimens and in the diffuse-type gastric cancer specimens; and in males aged ≤ 50 years compared with common GG genotype, TFF3 rs9981660 AA+AG genotypes were associated with TFF3 mRNA levels in diffuse-type gastric cancer tissues and their corresponding non-cancerous tissues. To our knowledge, this is the first report of an association between the TFF2 rs3814896 AG+GG genotypes and decreased risks of GC, diffuse-type GC, and atrophic gastritis in younger people aged ≤ 50 years, and an association between TFF3 rs9981660 AG+AA genotype and decreased risk of diffuse-type GC in men. Moreover, we found that TFF2 rs3814896 AG+GG genotypes in people aged ≤ 50 years and TFF3 rs9981660 AG+AA genotypes in younger males with diffuse-type GC were associated with higher levels of

  2. HOGG1 polymorphism in atrophic gastritis and gastric cancer after Helicobacter pylori eradication

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the association between Ser326Cys human oxoguanine glycosylase 1(hOGG1) polymorphism and atrophic gastritis and gastric cancer after Helicobacter pylori(H.pylori) eradication.METHODS:A total of 488 subjects(73 patients with gastric cancer,160 with atrophic gastritis after H.pylori eradication and 255 controls) were prospectively collected.Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to distinguish hOGG1 Ser326Cys polymorphism.Statistical analys...

  3. Autoimmune-mediated peripheral neuropathies and autoimmune pain.

    Science.gov (United States)

    Klein, Christopher J

    2016-01-01

    Peripheral neuropathies have diverse acquired and inherited causes. The autoimmune neuropathies represent an important category where treatment is often available. There are overlapping signs and symptoms between autoimmune neuropathies and other forms. Making a diagnosis can be challenging and first assisted by electrophysiologic and sometimes pathologic sampling, with autoimmune biomarkers providing increased assistance. Here we provide a review of the autoimmune and inflammatory neuropathies, their available biomarkers, and approaches to treatment. Also discussed is new evidence to support a mechanism of autoimmune pain.

  4. Autoimmunity in Immunodeficiency

    Science.gov (United States)

    Todoric, Krista; Koontz, Jessica B.; Mattox, Daniel; Tarrant, Teresa K.

    2013-01-01

    Primary immunodeficiencies (PID) comprise a diverse group of clinical disorders with varied genetic defects. Paradoxically, a substantial proportion of PID patients develop autoimmune phenomena in addition to having increased susceptibility to infections from their impaired immunity. Although much of our understanding comes from data gathered through experimental models, there are several well-characterized PID that have improved our knowledge of the pathways that drive autoimmunity. The goals of this review will be to discuss these immunodeficiencies and to review the literature with respect to the proposed mechanisms for autoimmunity within each put forth to date. PMID:23591608

  5. [Non-autoimmune thyroiditis].

    Science.gov (United States)

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

    2014-01-01

    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.

  6. Regulatory T-cells and autoimmunity.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh

    2012-02-03

    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.

  7. Human Cytomegalovirus and Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Anne Halenius

    2014-01-01

    Full Text Available Human cytomegalovirus (HCMV represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE, systemic sclerosis (SSc, diabetes mellitus type 1, and rheumatoid arthritis (RA is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.

  8. Autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Pietro Invernizzi; Ian R Mackay

    2008-01-01

    The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise 'pairs of articles' on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.

  9. Autoimmunity against laminins.

    Science.gov (United States)

    Florea, Florina; Koch, Manuel; Hashimoto, Takashi; Sitaru, Cassian

    2016-09-01

    Laminins are ubiquitous constituents of the basement membranes with major architectural and functional role as supported by the fact that absence or mutations of laminins lead to either lethal or severely impairing phenotypes. Besides genetic defects, laminins are involved in a wide range of human diseases including cancer, infections, and inflammatory diseases, as well as autoimmune disorders. A growing body of evidence implicates several laminin chains as autoantigens in blistering skin diseases, collagenoses, vasculitis, or post-infectious autoimmunity. The current paper reviews the existing knowledge on autoimmunity against laminins referring to both experimental and clinical data, and on therapeutic implications of anti-laminin antibodies. Further investigation of relevant laminin epitopes in pathogenic autoimmunity would facilitate the development of appropriate diagnostic tools for thorough characterization of patients' antibody specificities and should decisively contribute to designing more specific therapeutic interventions.

  10. Risk of Celiac Disease Autoimmunity is Modified by Non-HLA Genetic Markers During the First Year of Clinical Type 1 Diabetes

    DEFF Research Database (Denmark)

    Adlercreutz, Emma H.; Hansen, Dorthe; Mortensen, Henrik B.

    2014-01-01

    Aims: This study plotted the prevalence of celiac disease associated antibodies in relation to demographic patterns, genetic and metabolic markers during the first year after diagnosis in a multinational cohort of children with T1D. Material and Methods: Sera from a total of 261 children (128 males...... measuring IgG-tTG. Children positive in both assays in two consecutive samples were defined as having celiac disease autoimmunity (CDA). Associations between CDA and genotypes of HLA, IL18 rap, CCR 5, PTPN2 and correlations with islet autoantibodies (ICA, GADA, IA2 and IA) and HbA1C and C-peptide were...

  11. Autoimmunity in 2014.

    Science.gov (United States)

    Selmi, Carlo

    2015-10-01

    Our PubMed search for peer-reviewed articles published in the 2014 solar year retrieved a significantly higher number of hits compared to 2013 with a net 28 % increase. Importantly, full articles related to autoimmunity constitute approximately 5 % of immunology articles. We confirm that our understanding of autoimmunity is becoming a translational paradigm with pathogenetic elements rapidly followed by new treatment options. Furthermore, numerous clinical and pathogenetic elements and features are shared among autoimmune diseases, and this is well illustrated in the recent literature. More specifically, the past year witnessed critical revisions of our understanding and management of antiphospholipid syndrome with new exciting data on the pathogenicity of the serum anti-beta2 glycoprotein autoantibody, a better understanding of the current and new treatments for rheumatoid arthritis, and new position papers on important clinical questions such as vaccinations in patients with autoimmune disease, comorbidities, or new classification criteria. Furthermore, data confirming the important connections between innate immunity and autoimmunity via toll-like receptors or the critical role of T regulatory cells in tolerance breakdown and autoimmunity perpetuation were also reported. Lastly, genetic and epigenetic data were provided to confirm that the mosaic of autoimmunity warrants a susceptible individual background which may be geographically determined and contribute to the geoepidemiology of diseases. The 2014 literature in the autoimmunity world should be cumulatively regarded as part of an annus mirabilis in which, on a different level, the 2014 Annual Meeting of the American College of Rheumatology in Boston was attended by over 16,000 participants with over selected 3000 abstracts.

  12. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

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

    2015-10-01

    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.

  13. Lithium associated autoimmune thyroiditis.

    OpenAIRE

    Shimizu, M; Hirokawa, M.; T. Manabe; Shimozuma, K; Sonoo, H; Harada, T.

    1997-01-01

    A case of autoimmune thyroiditis after long term treatment with lithium is described in a 29 year old Japanese woman with manic depression. Positive serum antithyroglobulin and antimicrosomal antibodies, diffuse goitre, and microscopic chronic thyroiditis, as well as the clinical history of long term lithium treatment were suggestive of lithium associated autoimmune thyroiditis. Microscopically, there was a mild degree of interstitial fibrosis and a moderate degree of lymphocytic infiltration...

  14. The epigenetics of autoimmunity

    Science.gov (United States)

    Meda, Francesca; Folci, Marco; Baccarelli, Andrea; Selmi, Carlo

    2011-01-01

    The etiology of autoimmune diseases remains largely unknown. Concordance rates in monozygotic twins are lower than 50% while genome-wide association studies propose numerous significant associations representing only a minority of patients. These lines of evidence strongly support other complementary mechanisms involved in the regulation of genes expression ultimately causing overt autoimmunity. Alterations in the post-translational modification of histones and DNA methylation are the two major epigenetic mechanisms that may potentially cause a breakdown of immune tolerance and the perpetuation of autoimmune diseases. In recent years, several studies both in clinical settings and experimental models proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically, data support the impact of epigenetic changes in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases, in some cases based on mechanistical observations. We herein discuss what we currently know and what we expect will come in the next future. Ultimately, epigenetic treatments already being used in oncology may soon prove beneficial also in autoimmune diseases. PMID:21278766

  15. Autoimmunity in 2015.

    Science.gov (United States)

    Selmi, Carlo

    2016-08-01

    Compared to the clear trend observed in previous years, the number of peer-reviewed articles published during 2015 and retrieved using the "autoimmunity" key word declined by 4 %, while remaining 5 % of immunology articles. On the other hand, a more detailed analysis of the published articles in leading immunology and autoimmunity journals revealed exciting scenarios, with fascinating lines of evidence being supported by convincing data and likely followed by rapid translational or clinical developments. As examples, the study of the microbiome, the development of new serum or other tissue biomarkers, and a more solid understanding of disease pathogenesis and tolerance breakdown mechanisms have been central issues in the past year. Furthermore and similar to the oncology field, progress in the understanding of single autoimmune condition is becoming most specific with psoriatic and rheumatoid arthritis being ideal paradigms with treatment options diverging after decades of common therapies, as illustrated by IL17-targeting approaches. The ultimate result of these advances is towards personalized medicine with an ideal approach being tailored on a single patient, based on a finely tuned definition of the immunogenetics, epigenetics, microbiome, and biomarkers. Finally, experimental reports suggest that cancer-associated immune mechanisms or the role of T and B cell subpopulations should be better understood in autoimmune diseases. While we hailed the 2014 literature in the autoimmunity world as part of an annus mirabilis, we should not be mistaken in the strong stimulus of research in autoimmunity represented by the 2015 articles that will be summarized in this article.

  16. Vaccines and autoimmunity.

    Science.gov (United States)

    De Martino, M; Chiappini, E; Galli, L

    2013-01-01

    Vaccines have eradicated or controlled many infectious diseases, saving each year millions of lives and quality of life of many other millions of people. In spite of the success of vaccines over the last two centuries, parents (and also some health care workers) gloss over the devastating consequences of diseases, which are now avoided thanks to vaccines, and direct their attention to possible negative effects of immunization. Three immunological objections are raised: vaccines cause antigenic overload, natural immunity is safer and better than vaccine-induced immunity, and vaccines induce autoimmunity. The last point is examined in this review. Theoretically, vaccines could trigger autoimmunity by means of cytokine production, anti-idiotypic network, expression of human histocompatibility leukocyte antigens, modification of surface antigens and induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, and polyclonal activation of B cells. There is strong evidence that none of these mechanisms is really effective in causing autoimmune diseases. Vaccines are not a source of autoimmune diseases. By contrast, absolute evidence exists that infectious agents can trigger autoimmune mechanisms and that they do cause autoimmune diseases.

  17. Autoimmunity in 2013.

    Science.gov (United States)

    Selmi, Carlo

    2014-08-01

    The peer-reviewed publications in the field of autoimmunity published in 2013 represented a significant proportion of immunology articles and grew since the previous year to indicate that more immune-mediated phenomena may recognize an autoimmune mechanism and illustrated by osteoarthritis and atherosclerosis. As a result, our understanding of the mechanisms of autoimmunity is becoming the paradigm for translational research in which the progress in disease pathogenesis for both tolerance breakdown and inflammation perpetuation is rapidly followed by new treatment approaches and clinical management changes. The similarities across the autoimmune disease spectrum outnumber differences, particularly when treatments are compared. Indeed, the therapeutics of autoimmune diseases are based on a growing armamentarium that currently includes monoclonal antibodies and small molecules which act by targeting molecular markers or intracellular mediators with high specificity. Among the over 100 conditions considered as autoimmune, the common grounds are well illustrated by the data reported for systemic lupus erythematosus and rheumatoid arthritis or by the plethora of studies on Th17 cells and biomarkers, particularly serum autoantibodies. Further, we are particularly intrigued by studies on the genomics, epigenetics, and microRNA at different stages of disease development or on the safe and effective use of abatacept acting on the costimulation of T and B cells in rheumatoid arthritis. We are convinced that the data published in 2013 represent a promising background for future developments that will exponentially impact the work of laboratory and clinical scientists over the next years.

  18. Rapidly evolving hypopituitarism in a boy with multiple autoimmune disorders.

    Science.gov (United States)

    Jevalikar, Ganesh; Wong, Sze Choong; Zacharin, Margaret

    2013-09-01

    A 10-year-old boy with acute onset cranial diabetes insipidus and multiple autoimmune disorders had evolving panhypopituitarism, thought to be due to autoimmune hypophysitis. Over 18 months, a dramatic clinical course with progressive hypopituitarism and development of type 1 diabetes mellitus was evident. Serial brain imaging showed changes suggestive of germinoma.

  19. Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves

    NARCIS (Netherlands)

    Groen, R J; Sie, O G; van Weerden, T W

    1993-01-01

    The clinical, electrophysiological, radiological and morphological data of 3 members of a family with autosomal dominant distal spinal muscular atrophy (DSMA) are reported. One patient has the clinical picture of peroneal muscular atrophy with atrophic calves. His father and sister suffer from cramp

  20. The serological gastric biopsy in primary care : studies on atrophic gastritis

    NARCIS (Netherlands)

    Korstanje, Andries

    2006-01-01

    This thesis sheds light on the clinical utility of serum markers of gastric atrophy, pepsinogen and gastrin, in general practice in the Dutch province of Zeeland. The biomarkers were used in studies on atrophic corpus gastritis, as surrogate outcome of gastric cancer. Attention was paid to seroepide

  1. Clinical Research on Acupuncture and Moxibustion Treatment of Chronic Atrophic Gastritis

    Institute of Scientific and Technical Information of China (English)

    Gao Xiyan; Yuan Jing; Li Huijuan; Ren Shan

    2007-01-01

    Objective: To observe the clinical therapeutic effects of acupuncture and moxibustion in treating chronic atrophic gastritis. Methods: Patients who met the criteria were randomly divided into the treatment groups consisting of the acupuncture group (30 cases) and the acupuncture-moxibustion group (30 cases), and the control group (28 cases). After two months of treatment, observed were safety and the curative effects,through general physical check ups, routine examinations of blood, urine and feces, and symptoms,pathology and gastrin before, during and after the treatment. Results: 1) The treatment groups showed significant superiorities in the improvement of symptoms, with the acupuncture-moxibustion group showing the best therapeutic effects. 2) The acupuncture-moxibustion group showed marked differences before and after the treatment in the improvement of glandular atrophy and intestinal metaplasia, with a total effective rate of 66.67%. 3) After the treatment, the three groups all showed marked improvement in the level of serum gastrin, with the acupuncture-moxibustion group showing the best effects. Conclusion: Acupuncture and moxibustion have definite therapeutic effects for chronic atrophic gastritis, especially in improving the symptoms. Acupuncture or acupuncture combined with moxibustion can provide possibilities in reversing the pathologic changes of glandular atrophy and intestinal metaplasia for patients with chronic atrophic gastritis. Acupuncture-moxibustion is really an effective and safe therapy for chronic atrophic gastritis.

  2. Differential expression of phospholipase C epsilon 1 is associated with chronic atrophic gastritis and gastric cancer.

    Directory of Open Access Journals (Sweden)

    Jun Chen

    Full Text Available BACKGROUND: Chronic inflammation plays a causal role in gastric tumor initiation. The identification of predictive biomarkers from gastric inflammation to tumorigenesis will help us to distinguish gastric cancer from atrophic gastritis and establish the diagnosis of early-stage gastric cancer. Phospholipase C epsilon 1 (PLCε1 is reported to play a vital role in inflammation and tumorigenesis. This study was aimed to investigate the clinical significance of PLCε1 in the initiation and progression of gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: Firstly, the mRNA and protein expression of PLCε1 were analyzed by reverse transcription-PCR and Western blotting in normal gastric mucous epithelial cell line GES-1 and gastric cancer cell lines AGS, SGC7901, and MGC803. The results showed both mRNA and protein levels of PLCε1 were up-regulated in gastric cancer cells compared with normal gastric mucous epithelial cells. Secondly, this result was confirmed by immunohistochemical detection in a tissue microarray including 74 paired gastric cancer and adjacent normal tissues. Thirdly, an independence immunohistochemical analysis of 799 chronic atrophic gastritis tissue specimens demonstrated that PLCε1 expression in atrophic gastritis tissues were down-regulated since PLCε1 expression was negative in 524 (65.6% atrophic gastritis. In addition, matched clinical tissues from atrophic severe gastritis and gastric cancer patients were used to further confirm the previous results by analyzing mRNA and protein levels expression of PLCε1 in clinical samples. CONCLUSIONS/SIGNIFICANCES: Our results suggested that PLCε1 protein may be a potential biomarker to distinguish gastric cancer from inflammation lesion, and could have great potential in applications such as diagnosis and pre-warning of early-stage gastric cancer.

  3. Increased expression of intranuclear matrix metalloproteinase 9 in atrophic renal tubules is associated with renal fibrosis.

    Directory of Open Access Journals (Sweden)

    Jen-Pi Tsai

    Full Text Available BACKGROUND: Reduced turnover of extracellular matrix has a role in renal fibrosis. Matrix metalloproteinases (MMPs is associated with many glomerular diseases, but the histological association of MMPs and human renal fibrosis is unclear. METHODS: This is a retrospective study. Institutional Review Board approval was obtained for the review of patients' medical records, data analysis and pathological specimens staining with waiver of informed consents. Specimens of forty-six patients were examined by immunohistochemical stain of MMP-9 in nephrectomized kidneys, and the association of renal expression of MMP-9 and renal fibrosis was determined. MMP-9 expression in individual renal components and fibrosis was graded as high or low based on MMP-9 staining and fibrotic scores. RESULTS: Patients with high interstitial fibrosis scores (IFS and glomerular fibrosis scores (GFS had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR, and were more likely to have chronic kidney disease (CKD and urothelial cell carcinoma. Univariate analysis showed that IFS and GFS were negatively associated with normal and atrophic tubular cytoplasmic MMP-9 expression and IFS was positively correlated with atrophic tubular nuclear MMP-9 expression. Multivariate stepwise regression indicated that MMP-9 expression in atrophic tubular nuclei (r = 0.4, p = 0.002 was an independent predictor of IFS, and that MMP-9 expression in normal tubular cytoplasm (r = -0.465, p<0.001 was an independent predictor of GFS. CONCLUSIONS: Interstitial fibrosis correlated with MMP-9 expression in the atrophic tubular nuclei. Our results indicate that renal fibrosis is associated with a decline of MMP-9 expression in the cytoplasm of normal tubular cells and increased expression of MMP-9 in the nuclei of tubular atrophic renal tubules.

  4. Autoimmune thyroid disease and other non-endocrine autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Todorović-Đilas Ljiljana

    2011-01-01

    Full Text Available Introduction, 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. Autoimmune 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. Conclusions. 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.

  5. Protective effects of heat shock protein70 induced by geranyl-geranylacetone in atrophic gastritis in rats

    Institute of Scientific and Technical Information of China (English)

    Wei-li LIU; Shu-jie CHEN; Yan CHEN; Lei-min SUN; Wei ZHANG; Ya-min ZENG; Tian-hua ZHOU; Jian-min SI

    2007-01-01

    Aim: To investigate the effect of geranylgeranylacetone (GGA) on the progres-sion of atrophic gastritis in rats and its potential mechanism. Methods: Atrophic gastritis was induced in Sprague-Dawley rats with 0.1% ammonia solution, 60% ethanol, and 20 mmol/L deoxycholic acid for 24 weeks. Accompanied by the induction of atrophic gastritis, 200 mg/kg GGA was administered by oral gavage for 8 weeks (weeks 17-24). The histological changes in gastric mucosa were quantitated by the index of inflammation, the gastric mucosal thickness, and the amount of glands of 1 mm horizontal length in antrum. Endogenous heat shock protein (HSP)70 levels and distribution were determined by immunoblotting and immunohistochemistry in gastric mucosa. Results: GGA alleviated the pathologi-cal progression of atrophic gastritis with inflammation relief (inflammation index: 1.40 in the GGA group and 1.65 in the atrophic gastritis group) and glandular restoration (rnucosal thickness and quantity of glands: 194.3 μm and 38.7 mm in the GGA group; 123.3 μm and 32.7 mm in the atrophic gastritis group; P<0.05). GGA significantly induced HSP70 synthesis (P<0.05). Moreover, quercetin, an inhibitor of HSP70 expression, aggravated the infiltration of inflammatory cells and glandular loss in the antrum. Conclusion: GGA prevented the progression of atrophic gastritis in rats via the induction of HSP70 expression.

  6. Progress in molecular genetics in autoimmune polyendocrinopathy syndrome type Ⅰ%自身免疫性多内分泌腺病综合征Ⅰ型分子遗传学研究进展

    Institute of Scientific and Technical Information of China (English)

    刘彩虹; 石岩

    2010-01-01

    自身免疫性多内分泌腺病综合征Ⅰ型(APS-Ⅰ)是一种罕见的常染色体隐性遗传病,致病基因为自身免疫调节因子基因.已报道的致病性突变包括无义突变、错义突变、沉默突变、插入和缺失以及剪接位点突变等,该文就APS-Ⅰ致病基因的突变特征归纳综述.%Autoimmune polyendocrinopathy syndrome type Ⅰ( APS-Ⅰ) is a rare autosomal recessive disorder caused by mutations in autoimmune regulator gene( AIRE) . A number of mutations have been described in the AIRE gene of patients with APS-Ⅰ, including nonsense mutation, missense mutation, silent mutation, splice site mutation, insertions and deletions mutation, et al. The mutation characteristics of the APS-Ⅰ pathogenic gene have been reviewed in the article.

  7. Role of IgE in autoimmunity.

    Science.gov (United States)

    Sanjuan, Miguel A; Sagar, Divya; Kolbeck, Roland

    2016-06-01

    There is accumulating evidence to suggest that IgE plays a significant role in autoimmunity. The presence of circulating self-reactive IgE in patients with autoimmune disorders has been long known but, at the same time, largely understudied. However, studies have shown that the increased IgE concentration is not associated with higher prevalence for atopy and allergy in patients with autoimmune diseases, such as systemic lupus erythematosus. IgE-mediated mechanisms are conventionally known to facilitate degranulation of mast cells and basophils and promote TH2 immunity, mechanisms that are not only central to mounting an appropriate defense against parasitic worms, noxious substances, toxins, venoms, and environmental irritants but that also trigger exuberant allergic reactions in patients with allergies. More recently, IgE autoantibodies have been recognized to participate in the self-inflicted damaging immune responses that characterize autoimmunity. Such autoimmune responses include direct damage on tissue-containing autoantigens, activation and migration of basophils to lymph nodes, and, as observed most recently, induction of type 1 interferon responses from plasmacytoid dendritic cells. The importance of IgE as a central pathogenic mechanism in autoimmunity has now been clinically validated by the approval of omalizumab, an anti-IgE mAb, for patients with chronic spontaneous urticaria and for the clinical benefit of patients with bullous pemphigoid. In this review we summarize recent reports describing the prevalence of self-reactive IgE and discuss novel findings that incriminate IgE as central in the pathogenesis of inflammatory autoimmune disorders.

  8. Complement and autoimmunity.

    Science.gov (United States)

    Ballanti, Eleonora; Perricone, Carlo; Greco, Elisabetta; Ballanti, Marta; Di Muzio, Gioia; Chimenti, Maria Sole; Perricone, Roberto

    2013-07-01

    The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.

  9. Vaccines and autoimmunity.

    Science.gov (United States)

    Agmon-Levin, Nancy; Paz, Ziv; Israeli, Eitan; Shoenfeld, Yehuda

    2009-11-01

    Vaccines have been used for over 200 years and are the most effective way of preventing the morbidity and mortality associated with infections. Like other drugs, vaccines can cause adverse events, but unlike conventional medicines, which are prescribed to people who are ill, vaccines are administered to healthy individuals, thus increasing the concern over adverse reactions. Most side effects attributed to vaccines are mild, acute and transient; however, rare reactions such as hypersensitivity, induction of infection, and autoimmunity do occur and can be severe and even fatal. The rarity and subacute presentation of post-vaccination autoimmune phenomena means that ascertaining causality between these events can be difficult. Moreover, the latency period between vaccination and autoimmunity ranges from days to years. In this article, on the basis of published evidence and our own experience, we discuss the various aspects of the causal and temporal interactions between vaccines and autoimmune phenomena, as well as the possible mechanisms by which different components of vaccines might induce autoimmunity.

  10. Pregnancy with autoimmune hepatitis

    Science.gov (United States)

    Braga, António Costa; Vasconcelos, Carlos; Braga, Jorge

    2016-01-01

    Aim: The aim of this study was to review our experience with gestations in autoimmune hepatitis patients. Background: There are only limited data describing pregnancy in patients with autoimmune hepatitis. Patients and methods: Retrospective analysis of pregnancies with autoimmune hepatitis followed in Centro Hospitalar do Porto, Portugal in the last ten years. Results: We reported nine pregnancies in seven patients with autoimmune hepatitis. Two patients had documented liver cirrhosis prior to the pregnancy. In this study, 66.7% of patients were treated with azathioprine and 88.9% with prednisolone. Clinical improvements were observed in 11.1% of pregnancies and 22.2% exacerbations were diagnosed. There were six live births and two preterm deliveries (preterm delivery rate of 33%). We also report three first trimester miscarriages (early gestation miscarriage rate of 33%). There were no neonatal or maternal deaths. Conclusion: The favorable obstetric outcome is a realistic expectation in patients with autoimmune hepatitis. Tight monitoring and control of asymptomatic and unpredictable exacerbations, which are unrelated to the severity of the underlying disease, are essential to the prognosis of the current pregnancy. PMID:27458515

  11. Autoimmune pancreatitis--recent advances.

    Science.gov (United States)

    Novotný, I; Díte, P; Lata, J; Nechutová, H; Kianicka, B

    2010-01-01

    Autoimmune pancreatitis (AIP) is recognized as a distinct clinical entity, identified as a chronic inflammatory process of the pancreas in which the autoimmune mechanism is involved. Clinically and histologically, AIP has two subsets: type 1--lymphoplasmatic sclerosing pancreatitis with abundant infiltration of the pancreas and other affected organs with immunoglobulin G4-positive plasma cells, and type 2--duct centric fibrosis, characterized by granulocyte epithelial lesions in the pancreas without systemic involvement. In the diagnosis of AIP, two diagnostic criterions are used--the HISORt criteria and Asian Diagnostic Criteria. In the differential diagnosis, the pancreatic cancer must be excluded by endosonographically guided pancreatic biopsy. Typical signs of AIP are concomitant disorders in other organs (kidney, liver, biliary tract, salivary glands, colon, retroperitoneum, prostate). Novel clinicopathological entity was proposed as an 'IgG4-related sclerosing disease' (IgG4-RSC). Extensive IgG4-positive plasma cells and T lymphocyte infiltration is a common characteristics of this disease. Recently, IgG4-RSC syndrome was extended to a new entity, characterized by IgG4 hypergammaglobulinemia and IgG4-positive plasma cell infiltration, this being considered an expression of a lymphoproliferative disease, 'IgG4-positive multiorgan lymphoproliferative syndrome'. This syndrome includes Mikulicz's disease, mediastinal fibrosis, autoimmune hypophysitis, and inflammatory pseudotumor--lung, liver, breast. In the therapy of AIP, steroids constitute first-choice treatment. High response to the corticosteroid therapy is an important diagnostic criterion. In the literature, there are no case-control studies that determine if AIP predisposes to pancreatic cancer. Undoubtedly, AIP is currently a hot topic in pancreatology.

  12. Early Childhood Infections and the Risk of Islet Autoimmunity

    OpenAIRE

    Snell-Bergeon, Janet K.; Smith, Jennifer; Dong, Fran; Barón, Anna E.; Barriga, Kathy; Norris, Jill M.; Rewers, Marian

    2012-01-01

    OBJECTIVE Type 1 diabetes is a common chronic childhood disease, and the incidence is increasing globally. Childhood infections are considered a potential environmental trigger of type 1 diabetes. Alternatively, improved hygiene and reduced childhood infections could explain the increase in type 1 diabetes in developed countries. The association of reported illnesses during infancy and later development of islet autoimmunity (IA) were examined in the Diabetes Autoimmunity Study in the Young. ...

  13. Headache in autoimmune diseases.

    Science.gov (United States)

    John, Seby; Hajj-Ali, Rula A

    2014-03-01

    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.

  14. Autoimmun synaptisk encefalitis er en underdiagnosticeret sygdomsgruppe

    DEFF Research Database (Denmark)

    Nielsen, Signe Modvig; Høi-Hansen, Christina Engel; Uldall, Peter;

    2012-01-01

    The term autoimmune synaptic encephalitis (ASE) comprises encephalitides associated with autoantibodies against structures of the neuronal synapse. We review four types of ASE (anti-N-methyl-D-aspartate receptor encephalitis, anti-α-amine-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor enc...

  15. Common mechanisms of autoimmune diseases (the autoimmune tautology).

    Science.gov (United States)

    Anaya, Juan-Manuel

    2012-09-01

    The fact that autoimmune diseases share subphenotypes, physiopathological mechanisms and genetic factors has been called autoimmune tautology, and indicates that they have a common origin. The autoimmune phenotypes vary depending on the target cell and the affected organ, gender, ancestry, trigger factors and age at onset. Ten shared characteristics supporting this logical theory are herein reviewed.

  16. [Autoimmune hemolytic anemia in children].

    Science.gov (United States)

    Becheur, M; Bouslama, B; Slama, H; Toumi, N E H

    2015-01-01

    Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options.

  17. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis

    NARCIS (Netherlands)

    Capelle, Lisette G.; de Vries, Annemarie C.; Haringsma, Jelle; Ter Borg, Frank; de Vries, Richard A.; Bruno, Marco J.; van Dekken, Herman; Meijer, Jos; van Grieken, Nicole C. T.; Kuipers, Ernst J.

    2010-01-01

    Background: The OLGA (operative link on gastritis assessment) staging system is based on severity of atrophic gastritis (AG). AG remains a difficult histopathologic diagnosis with low interobserver agreement, whereas intestinal metaplasia (IM) is associated with high interobserver agreement. Objecti

  18. Efficacy of tepronone and folic acid in the treatment of chronic atrophic gastritis evaluated by the marking targeting biopsy

    Institute of Scientific and Technical Information of China (English)

    裘力锋

    2013-01-01

    Objective To explore the efficacy of tepronone and folic acid in the treatment of chronic atrophic gastritis(CAG) evaluated by the marking targeting biopsy(MTB).Methods A total of 224 H.pylori negative

  19. 自身免疫性多内分泌腺病综合征4型一例报道并文献复习%Autoimmune Polyendocrine Syndrome Type 4:A Case Report and Literature Review

    Institute of Scientific and Technical Information of China (English)

    李新杰; 周玉森; 张允

    2015-01-01

    自身免疫性多内分泌腺病综合征( APS)是指以2个或2个以上的内分泌腺体因自身免疫功能缺陷而发生功能受损为主要表现的一系列综合征,亦可累及非内分泌腺器官。本文报道了1例APS-4型患者先后出现脱毛症、溃疡性结肠炎、1型糖尿病、促肾上腺皮质激素( ACTH)缺乏型腺垂体功能减退。APS-4型是一种少见的综合征,常伴有多种内分泌腺功能减退,要注意补充一种激素的同时可能影响另一种疾病的治疗。%Autoimmune polyendocrine syndrome(APS)refers to the dysfunction of two or more endocrine glandsdue to the deficiency of autoimmune function,also involving non-endocrine organs. The paper reported a case of APS-4 patient who had alopecia,ulcerative colitis,type 1 diabetes mellitus and ACTH-deficient hypopituitarism successively. APS-4 type is a rare syndrome concurrent with multiple kinds of hypopituitarism. Attention should be given that the supplement of one hormone may affect the treatment of another disease.

  20. Diagnostic criteria of autoimmune hepatitis.

    Science.gov (United States)

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

    2014-01-01

    Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disorder characterised by female preponderance, elevated transaminase and immunoglobulin G levels, seropositivity for autoantibodies and interface hepatitis. Presentation is highly variable, therefore AIH should be considered during the diagnostic workup of any increase in liver enzyme levels. A set of inclusion and exclusion criteria for the diagnosis of AIH have been established by the International Autoimmune Hepatitis Group (IAIHG). There are two main types of AIH: type 1, positive for anti-nuclear (ANA) and/or anti-smooth muscle antibodies (SMAs) and type 2, defined by the presence of anti-liver kidney microsomal antibody type 1 (LKM-1) and/or anti-liver cytosol type 1 (LC-1) autoantibodies. The central role of autoantibodies in the diagnosis of AIH has led the IAIHG to produce a consensus statement detailing appropriate and effective methods for their detection. Autoantibodies should be tested by indirect immunofluorescence at an initial dilution of 1/40 in adults and 1/10 in children on a freshly prepared rodent substrate that includes kidney, liver and stomach sections to allow for the simultaneous detection of all reactivities relevant to AIH. Anti-LKM-1 is often confused with anti-mitochondrial antibody (AMA) if rodent kidney is used as the sole immunofluorescence substrate. The identification of the molecular targets of anti-LKM-1 and AMA has led to the establishment of immuno-assays based on the use of the recombinant or purified autoantigens. Perinuclear anti-nuclear neutrophil antibody (p-ANNA) is an additional marker of AIH-1; anti soluble liver antigen (SLA) antibodies are specific for autoimmune liver disease, can be present in AIH-1 and AIH-2 and are associated with a more severe clinical course. Anti-SLA are detectable by ELISA or radio-immuno-assays, but not by immunofluorescence. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to

  1. Autoimmune muscular pathologies.

    Science.gov (United States)

    Dalakas, M C

    2005-05-01

    The T cell-mediated mechanism responsible for Polymyositis and inclusion Body Myositis and the complement-mediated microangiopathy associated with Dermatomyositis are reviewed. The management of autoimmune myopathies with the presently available immunotherapeutic agents as well as new therapies and ongoing trials are discussed.

  2. Fractional CO2 lasers for the treatment of atrophic acne scars: a review of the literature.

    Science.gov (United States)

    Magnani, Lauren Rose; Schweiger, Eric S

    2014-04-01

    This review examines the efficacy and safety of fractional CO2 lasers for the treatment of atrophic scarring secondary to acne vulgaris. We reviewed 20 papers published between 2008 and 2013 that conducted clinical studies using fractional CO2 lasers to treat atrophic scarring. We discuss the prevalence and pathogenesis of acne scarring, as well as the laser mechanism. The histologic findings are included to highlight the ability of these lasers to induce the collagen reorganization and formation that improves scar appearance. We considered the number of treatments and different laser settings to determine which methods achieve optimal outcomes. We noted unique treatment regimens that yielded superior results. An overview of adverse effects is included to identify the most common ones. We concluded that more studies need to be done using uniform treatment parameters and reporting in order to establish which fractional CO2 laser treatment approaches allow for the greatest scar improvement.

  3. IL-1β a potential factor for discriminating between thyroid carcinoma and atrophic thyroiditis.

    Science.gov (United States)

    Kammoun-Krichen, Maha; Bougacha-Elleuch, Noura; Mnif, Mouna; Bougacha, Fadia; Charffedine, Ilhem; Rebuffat, Sandra; Rebai, Ahmed; Glasson, Emilie; Abid, Mohamed; Ayadi, Fatma; Péraldi-Roux, Sylvie; Ayadi, Hammadi

    2012-01-01

    Interactions between cytokines and others soluble factors (hormones, antibodies...) can play an important role in the development of thyroid pathogenesis. The purpose of the present study was to examine the possible correlation between serum cytokine concentrations, thyroid hormones (FT4 and TSH) and auto-antibodies (Tg and TPO), and their usefulness in discriminating between different thyroid conditions. In this study, we investigated serum from 115 patients affected with a variety of thyroid conditions (44 Graves' disease, 17 Hashimoto's thyroiditis, 11 atrophic thyroiditis, 28 thyroid nodular goitre and 15 papillary thyroid cancer), and 30 controls. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Thyroid hormones and auto-antibodies were measured using ELISA. Our study showed that IL-1β serum concentrations allow the discrimination between atrophic thyroiditis and papillary thyroid cancer groups (p = 0.027).

  4. Clinical and Histological Results of Vertical Ridge Augmentation of Atrophic Posterior Mandible with Inlay Technique of Cancellous Equine Bone Blocks

    OpenAIRE

    Pistilli R; Barausse C; Checchi L; Nannmark U; Felice P

    2013-01-01

    Aim: We want to evaluate a new bone block material in the inlay technique, for the vertical bone augmentation of a posterior atrophic mandible, in order to perfom aesthetic and prosthetic rehabilitation and enable implant insertion. Materials & Methods: Inlay technique and the subsequent successful implant rehabilitation in the atrophic right posterior mandible in a 42-year-old woman, was completed using a cancellous equine bone block as grafting material. Results: Three months after ...

  5. INFLUENCE BILIARY DYSKINESIA ON RELIABLE CHAIR-TEST IN PATIENTS WITH CHRONIC NON-ATROPHIC GASTRITIS

    OpenAIRE

    Avramenko, A. A.; Korolenko, R N; Shuhtina, I. N.

    2017-01-01

    It was carried out a comprehensive survey of 45 patients with chronic non-atrophic gastritis with biliary dyskinesia, which included ultrasound diagnosis of abdominal organs, pH meters, esophagogastroduodenoscopy, double testing for H. pylori infection and histological examination of the gastric mucosa to 4 - m topographic zones, stool test and determine the level of antibodies to HP infection by ELISA. It was found that the presence of biliary dyskinesia reduces the reliability of the chair-...

  6. Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers

    OpenAIRE

    Agréus, Lars; Kuipers, Ernst J; Kupcinskas, Limas; Malfertheiner, Peter; Di Mario, Francesco; Leja, Marcis; Mahachai, Varocha; Yaron, Niv; Van Oijen, Martijn; Perez, Guillermo Perez; Rugge, Massimo; Ronkainen, Jukka; Salaspuro, Mikko; Sipponen, Pentti; Sugano, Kentaro

    2012-01-01

    Background and aims Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers. Methods The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice. Res...

  7. Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the effects of interleukin-8 (IL-8 ), macrophage migration inhibitory factor (MIF ) gene polymorphisms, Helicobacter pylori (H. pylori ) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on...

  8. 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.

  9. Influence of H pylori on plasma ghrelin in patients without atrophic gastritis

    Institute of Scientific and Technical Information of China (English)

    Mehmet Cindoruk; Ilhan Yetkin; Serpil Muge Deger; Tarkan Karakan; Erdal Kan; Selahattin Unal

    2007-01-01

    AIM: To determine the association between H pylori infection and serum ghrelin levels in patients without atrophic gastritis.METHODS: Fifty consecutive patients (24 males and 26 females) with either H pylori-positive gastritis (n = 34) or H pylori-negative gastritis (n = 16) with normal gastric acid secretion determined by 24-h pHmetry and without atrophic gastritis in histopathology were enrolled in this study. Thirty-four H pylori-infected patients were treated with triple therapy consisting of a daily regimen of 30 mg lansoprazole bid, 1 g amoxicillin bid and 500 mg clarithromycin bid for 14 d, followed by an additional 4 wk of 30 mg lansoprazol treatment. H pylori infection was eradicated in 23 of 34 (67.6%) patients. H pylori-positive patients were given eradication therapy. Gastric acidity was determined via intragastric pH catethers. Serum ghrelin was measured by radioimmunoassay (RIA).RESULTS: There was no significant difference in plasma ghrelin levels between H pylori -positive and H pylori-negative groups (81.10 ± 162.66 ng/L vs 76.51 ± 122.94 ng/L). In addition, there was no significant difference in plasma ghrelin levels and gastric acidity levels measured before and 3 mo after the eradication therapy.CONCLUSION: H pylori infection does not influence ghrelin secretion in patients with chronic gastritis without atrophic gastritis.

  10. Novel Immunotherapies for Autoimmune Hepatitis.

    Science.gov (United States)

    Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

    2017-01-01

    Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4(+) T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects.

  11. Novel Immunotherapies for Autoimmune Hepatitis

    Science.gov (United States)

    Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

    2017-01-01

    Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4+ T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects. PMID:28184367

  12. Propylthiouracil-induced autoimmune disease

    Directory of Open Access Journals (Sweden)

    Santosh Paiaulla

    2015-01-01

    Full Text Available Hyperthyroidism is a condition characterized by excessive production of thyroid hormones. Propylthiouracil (PTU is commonly used as first line drug in the management of hyperthyroidism. This is a case report of 24-year-old female, a known case of hyperthyroidism since 4 years, who came with a history of fever and myalgia since 3 days and dyspnea with coughing out of blood since 1 day. Patient was taking PTU (100 mg per day since 4 years for hyperthyroidism. Patient was immediately intubated for type-II respiratory failure. Diagnosed to be having PTU-induced autoimmune disease. PTU was stopped and treated with methylprednisolone and cyclophosphamide. Clinical features improved over a period of 8 days and discharged home successfully. Having a high suspicion for the onset of autoimmune disease in hyperthyroidism patients who are on PTU therapy and timely treatment with immunosuppressants and supportive care along with the withdrawal of the drug can make a difference in morbidity and mortality.

  13. Safety of vaccine adjuvants: focus on autoimmunity.

    Science.gov (United States)

    van der Laan, Jan Willem; Gould, Sarah; Tanir, Jennifer Y

    2015-03-24

    Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed.

  14. Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

    Science.gov (United States)

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

    2015-03-01

    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.

  15. Clinical and histological results in the treatment of atrophic and hypertrophic scars using a combined method of radiofrequency, ultrasound, and transepidermal drug delivery.

    Science.gov (United States)

    Trelles, Mario A; Martínez-Carpio, Pedro A

    2016-08-01

    Scars are problematic for thousands of patients. Scarring is a natural part of the healing process after an injury. However, the appearance of a scar and its treatment depend on multiple factors and on the experience of the therapist and the options available. Despite a plethora of rapidly evolving treatment options and technical advances, the management of atrophic and hypertrophic scars remains difficult. Innovative technologies provide an attractive alternative to conventional methods in the treatment of scars. The purpose of this trial was to determine the clinical and histological results of a method of treatment that combines radiofrequency, ultrasound, and transepidermal drug delivery. This was a prospective study conducted on 14 patients with scars of different sizes, types, and characteristics. All patients underwent six treatment sessions with the Legato device. Atrophic scars were treated with retinoic acid and hypertrophic scars with triamcinolone. Photographs and biopsies were taken before treatment and at 6 months after the last treatment session. The scars improved significantly (P < 0.0001). The mean attenuation in the severity of scars was 67% (range: 50-75%), where 100% indicates complete disappearance of the scar. Clinical and histological images of scar tissue in six patients in whom attenuation in the range of 55-75% was achieved are shown. Biopsies show regenerative changes in the scar tissue, in both the epidermis and dermis. The method makes it possible to treat extensive, heterogeneous scars on different sites with good results that are similar and predictable.

  16. Update on autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Andreas Teufel; Peter R Galle; Stephan Kanzler

    2009-01-01

    Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features, hyperglobulinemia (IgG), and the presence of circulating autoantibodies, as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years, a couple of new insights into the genetic aspects, clinical course and treatment of AIH have been reported, which will be the focus of this review. In particular, we concentrate on genome-wide microsatellite analysis, a novel mouse model of AIH, the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH, and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.

  17. Inheritance of autoimmune neuroinflammation

    OpenAIRE

    Stridh, Pernilla

    2010-01-01

    Multiple sclerosis (MS) is a chronic neuro-inflammatory disease with anticipated complex etiology. Susceptibility to MS is conferred by numerous genes, with very low odds ratios that explain minute fractions of disease. This indicates that unknown factors are responsible for the remaining genetic contribution, termed the missing heritability . Due to the similarities to MS pathogenesis, we studied myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune ...

  18. Autoimmune Progesterone Anaphylaxis

    Directory of Open Access Journals (Sweden)

    Mohammad Hassan Bemanian

    2007-06-01

    Full Text Available Progesterone induced dermatitis is a rare disorder. It typically occurs in females due to anautoimmune phenomenon to endogenous progesterone production, but can also be caused byexogenous intake of a synthetic progestin. Here in, we present a case of autoimmune progesterone anaphylaxis (AIPA observed in an adolescent female.The patient is an 18-year-old Caucasian female with no significant past medical history and noprior exogenous hormone use, who presented to her primary care physician complaining of cyclic skin eruptions with dyspnea, cough and respiratory distress. She noted that her symptoms occurred monthly, just prior to her menses. An intradermal skin test using 0.1 cml of progesterone was performed. The patient developed a 15mm wheal after 15 minutes, confirming the diagnosis of AIPA.The patient was started on a continuous regimen of an oral conjugated estrogen (0.625mg. The skin eruptions and respiratory symptoms have not returned since the initiation of this therapy.Autoimmune progesterone dermatitis manifests via the occurrence of cyclic skin eruptions.Women with the disorder commonly present with dermatologic lesions in the luteal phase of themenstrual cycle, if there are any other organ involvement in addition to skin (e.g. lung, GI thereaction should be called as autoimmune progesterone anaphylaxis. Diagnosis of AIPA is confirmed by performing a skin allergen test using progesterone.

  19. Complement in autoimmune diseases.

    Science.gov (United States)

    Vignesh, Pandiarajan; Rawat, Amit; Sharma, Madhubala; Singh, Surjit

    2017-02-01

    The complement system is an ancient and evolutionary conserved element of the innate immune mechanism. It comprises of more than 20 serum proteins most of which are synthesized in the liver. These proteins are synthesized as inactive precursor proteins which are activated by appropriate stimuli. The activated forms of these proteins act as proteases and cleave other components successively in amplification pathways leading to exponential generation of final effectors. Three major pathways of complement pathways have been described, namely the classical, alternative and lectin pathways which are activated by different stimuli. However, all the 3 pathways converge on Complement C3. Cleavage of C3 and C5 successively leads to the production of the membrane attack complex which is final common effector. Excessive and uncontrolled activation of the complement has been implicated in the host of autoimmune diseases. But the complement has also been bemusedly described as the proverbial "double edged sword". On one hand, complement is the final effector of tissue injury in autoimmune diseases and on the other, deficiencies of some components of the complement can result in autoimmune diseases. Currently available tools such as enzyme based immunoassays for functional assessment of complement pathways, flow cytometry, next generation sequencing and proteomics-based approaches provide an exciting opportunity to study this ancient yet mysterious element of innate immunity.

  20. Autoantibodies in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Daniel S. Smyk

    2012-01-01

    Full Text Available Autoimmune pancreatitis (AIP was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.

  1. Food/nutrient intake and risk of atrophic gastritis among the Helicobacter pylori-infected population of northeastern Japan.

    Science.gov (United States)

    Montani, Ai; Sasazuki, Shizuka; Inoue, Manami; Higuchi, Kazuhide; Arakawa, Tetsuo; Tsugane, Shoichiro

    2003-04-01

    Although Helicobacter pylori (H. pylori ) infection is considered a key risk factor for atrophic gastritis, along with other environmental factors, it is still unclear which factor is involved in the development of atrophic gastritis among H. pylori-infected subjects. In the present cross-sectional study, therefore, we analyzed various dietary factors in relation to the presence of atrophic gastritis among H. pylori-infected subjects who participated in a health check-up program in a town in northeastern Japan. One thousand and seventy-one subjects (362 males and 709 females) who provided both self-administered validated food frequency questionnaires and blood samples were the basis for the study, and all of them were serologically positive for H. pylori immunoglobulin G (IgG) antibody. Among them, 663 (223 males and 440 females) were diagnosed as having atrophic gastritis on the basis of serum pepsinogen levels. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated based on tertile categories of subjects without atrophic gastritis, using logistic regression analysis. Among females, high consumptions of rice (OR = 1.6, 95% CI: 1.1-2.3), cod roe (OR = 1.5, 95% CI: 1.0-2.2) and cuttlefish (OR = 1.5, 95% CI: 1.0-2.3) were associated with a moderately increased risk of atrophic gastritis after adjustment for age (P for trend = 0.02 for these items). Among males, high consumptions of rice and miso soup showed a tendency toward an increased risk (P for trend = 0.12 and 0.13, respectively). Vegetables and fruits showed no association among either males or females. From these results, it is suggested that the dietary habits of consumers of traditional Japanese foods may play a role in the development of atrophic gastritis after H. pylori infection.

  2. Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies.

    Science.gov (United States)

    Quaio, Caio R D C; Carvalho, Jozélio F; da Silva, Clovis A; Bueno, Cleonice; Brasil, Amanda S; Pereira, Alexandre C; Jorge, Alexander A L; Malaquias, Alexsandra C; Kim, Chong A; Bertola, Débora R

    2012-05-01

    The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment.

  3. The Effect of Pimecrolimus Cream 1% Compared with Triamcinolone Acetonide Paste in Treatment of Atrophic-Erosive Oral Lichen Planus

    Directory of Open Access Journals (Sweden)

    Atessa Pakfetrat

    2015-03-01

    Full Text Available Introduction: Oral lichen planus (OLP is a common chronic mucocutaneous disease. Patients with atrophic and erosive types of OLP often have symptoms of soreness, and require proper treatment. The main treatment for OLP has been the administration of topical or systemic corticosteroids. The objective of this study was to compare the efficacy of adcortyl cream (triamcinolone acetonide in orabase with topical pimecrolimus cream for the treatment of erosive OLP.   Materials and Methods: Twenty-eight patients with OLP were enrolled in a single blind clinical trial and assigned to either a pimecrolimus 1% cream group or an adcortyl 0.1% cream group. The medication was applied every day for 2 months and patients were assessed every 2 weeks.   Results: The mean lesion size and mean pain and burning sensation scores did not differ between the pimecrolimus and adcortyl cream groups. The pimecrolimus cream was well tolerated. No clinical drug-related adverse events were observed.   Conclusion:  Topical pimecrolimus cream may be recommended as a safe and effective alternative therapy in the treatment of OLP. Pimecrolimus cream is as effective as adcortyl cream in managing the signs and symptoms of OLP.

  4. Association between autoimmune pancreatitis and systemic autoimmune diseases

    Institute of Scientific and Technical Information of China (English)

    Viktória Terzin; Imre F(o)ldesi; László Kovács; Gyula Pokorny; Tibor Wittmann; László Czakó

    2012-01-01

    AIM:To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4).METHODS:The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment.Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and,in some cases,by computer tomography (CT).RESULTS:Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients.10 patients had Sj(o)gren's syndrome (SS) (IgG4:590 ±232 mg/L),2 of them in association with Hashimoto's thyroiditis,and 7 patients (IgG4:1388 ± 985.5 mg/L)had systemic lupus erythematosus (SLE).The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L).Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level.CONCLUSION:The serum IgG4 level may be elevated in SAIDs without the presence of AIP.The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.

  5. Roles of A20 in autoimmune diseases.

    Science.gov (United States)

    Zhang, Min; Peng, Ling-Long; Wang, Ying; Wang, Jian-Shu; Liu, Jiao; Liu, Meng-Meng; Hu, Jia; Song, Bin; Yang, Hai-Bing

    2016-04-01

    A20 (TNFAIP3), known to inhibit NF-κB function by deubiquitinating-specific NF-κB signaling molecules, has been found in many cell types of the immune system. Recent findings suggest that A20 is essential for the development and functional performance of dendritic cell, B cell, T cell and macrophage. A number of studies further demonstrate that these cells are crucial in the pathogenesis of autoimmune diseases, such as type 1 diabetes, systemic lupus erythematosus, inflammatory bowel disease, ankylosing arthritis, Sjögren's syndrome and rheumatoid arthritis. In this article, we focus on the recent advances on the roles of A20 in autoimmune diseases and discuss the therapeutic significance of these new findings.

  6. Diagnosis and classification of autoimmune diabetes mellitus.

    Science.gov (United States)

    Canivell, Silvia; Gomis, Ramon

    2014-01-01

    Diabetes mellitus is increasing in prevalence worldwide. The economic costs and burden of the disease are considerable given the cardiovascular complications and co-morbidities that it may entail. Two major groups of diabetes mellitus have been defined, type 1, or immune-based, and type 2. In recent years, other subgroups have been described in-between these major groups. Correct classification of the disease is crucial in order to ascribe the most efficient preventive, diagnostic and treatment strategies for each patient. In the present review, we discuss the epidemiology, etiopathogenesis, diagnostic criteria and clinical classification of what is currently known as autoimmune diabetes. In addition, the other groups of diabetes mellitus will be regarded in relation to their pathogenesis and potential autoimmunity features.

  7. Effects of He-Ne laser irradiation on chronic atrophic gastritis in rats

    Institute of Scientific and Technical Information of China (English)

    Xue-Hui Shao; Yue-Ping Yang; Jie Dai; Jing-Fang Wu; Ai-Hua Bo

    2005-01-01

    AIM: To study the effects of He-Ne laser irradiation on experimental chronic atrophic gastritis (CAG) in rats.METHODS: Sixty-three male adult Wistar rats were randomly divided into five groups including normal control group, model control group and three different dosages He-Ne laser groups. The chronic atrophic gastritis (CAG)model in rats was made by pouring medicine which was a kind of mixed liquor including 2% sodium salicylate and 30% alcohol down the throat for 8 wk to stimulate rat gastric mucosa, combining with irregular fasting and compulsive sporting as pathogenic factors; 3.36, 4.80, and 6.24J/cm2doses of He-Ne laser were used, respectively for three different treatment groups, once a day for 20 d. The pH value of diluted gastric acid was determined by acidimeter,the histopathological changes such as the inflammatory degrees in gastric mucosa, the morphology and structure of parietal cells were observed, and the thickness of mucosa was measured by micrometer under optical microscope.RESULTS: In model control group, the secretion of gastric acid was little, pathologic morphological changes in gastric mucosa such as thinner mucous, atrophic glands, notable inflammatory infiltration were found. After 3.36 J/cm2 dose of He-Ne laser treatment for 20 d, the secretion of gastric acid was increased (P<0.05), the thickness of gastric mucosa was significantly thicker than that in model control group (P<0.01), the gastric mucosal inflammation cells were decreased (P<0.05). Morphology, structure and volume of the parietal cells all recuperated or were closed to normal.CONCLUSION: 3.36J/cm2 dose of He-Ne laser has a significant effect on CAG in rats.

  8. Membranoproliferative glomerulonephritis associated with autoimmune diseases.

    Science.gov (United States)

    Zand, Ladan; Fervenza, Fernando C; Nasr, Samih H; Sethi, Sanjeev

    2014-04-01

    Membranoproliferative glomerulonephritis (MPGN) has been classified based on its pathogenesis into immune complex-mediated and complement-mediated MPGN. The immune complex-mediated type is secondary to chronic infections, autoimmune diseases or monoclonal gammopathy. There is a paucity of data on MPGN associated with autoimmune diseases. We reviewed the Mayo Clinic database over a 10-year period and identified 12 patients with MPGN associated with autoimmune diseases, after exclusion of systemic lupus erythematosus. The autoimmune diseases included rheumatoid arthritis, primary Sjögren's syndrome, undifferentiated connective tissue disease, primary sclerosing cholangitis and Graves' disease. Nine of the 12 patients were female, and the mean age was 57.9 years. C4 levels were decreased in nine of 12 patients tested. The serum creatinine at time of renal biopsy was 2.2 ± 1.0 mg/dl and the urinary protein was 2,850 ± 3,543 mg/24 h. Three patients required dialysis at the time of renal biopsy. Renal biopsy showed an MPGN in all cases, with features of cryoglobulins in six cases; immunoglobulin (Ig)M was the dominant Ig, and both subendothelial and mesangial electron dense deposits were noted. Median follow-up was 10.9 months. Serum creatinine and proteinuria improved to 1.6 ± 0.8 mg/dl and 428 ± 677 mg/24 h, respectively, except in 3 patients with end-stage renal disease. In summary, this study describes the clinical features, renal biopsy findings, laboratory evaluation, treatment and prognosis of MPGN associated with autoimmune diseases.

  9. Neuropathology of autoimmune encephalitides.

    Science.gov (United States)

    Bauer, Jan; Bien, Christian G

    2016-01-01

    In recent years a large number of antibody-associated or antibody-defined encephalitides have been discovered. These conditions are often referred to as autoimmune encephalitides. The clinical features include prominent epileptic seizures, cognitive and psychiatric disturbance. These encephalitides can be divided in those with antibodies against intracellular antigens and those with antibodies against surface antigens. The discovery of new antibodies against targets on the surface of neurons is especially interesting since patients with such antibodies can be successfully treated immunologically. This chapter focuses on the pathology and the pathogenetic mechanisms involved in these encephalitides and discusses some of the questions that are raised in this exciting new field. It is important to realise, however, that because of the use of antibodies to diagnose the patients, and their improvement with treatment, there are relatively few biopsy or postmortem reports, limiting the neuropathological data and conclusions that can be drawn. For this reason we especially focus on the most frequent autoimmune encephalitides, those with antibodies to the NMDA receptor and with antibodies to the known protein components of the VGKC complex. Analysis of these encephalitides show completely different pathogenic mechanisms. In VGKC complex encephalitis, antibodies seem to bind to their target and activate complement, leading to destruction and loss of neurons. On the other hand, in NMDAR encephalitis, complement activation and neuronal degeneration seems to be largely absent. Instead, binding of antibodies leads to a decrease of NMDA receptors resulting in a hypofunction. This hypofunction offers an explanation for some of the clinical features such as psychosis and episodic memory impairment, but not for the frequent seizures. Thus, additional analysis of the few human brain specimens present and the use of specific animal models are needed to further understand the effects

  10. Pasteurella multocida and Bordetella bronchiseptica in atrophic rhinitis and pneumonia in swine.

    OpenAIRE

    Cowart, R P; Bäckström, L; Brim, T A

    1989-01-01

    A total of 163 pigs from nine farrow-to-finish herds representing various levels of atrophic rhinitis (AR) were selected for postslaughter examination of AR and pneumonia. Nasal swabs and lungs were cultured for detection of Bordetella bronchiseptica and Pasteurella multocida. Seventy-three pigs were examined at eight weeks of age and 90 contemporaries at six months of age. Mean AR scores were 1.21 and 1.11 for the eight week and six month old pigs, respectively (0 = normal, 3 = severe). In i...

  11. Warm autoimmune hemolytic anemia.

    Science.gov (United States)

    Naik, Rakhi

    2015-06-01

    Warm autoimmune hemolytic anemia (AIHA) is defined as the destruction of circulating red blood cells (RBCs) in the setting of anti-RBC autoantibodies that optimally react at 37°C. The pathophysiology of disease involves phagocytosis of autoantibody-coated RBCs in the spleen and complement-mediated hemolysis. Thus far, treatment is aimed at decreasing autoantibody production with immunosuppression or reducing phagocytosis of affected cells in the spleen. The role of complement inhibitors in warm AIHA has not been explored. This article addresses the diagnosis, etiology, and treatment of warm AIHA and highlights the role of complement in disease pathology.

  12. Autoimmune hepatitis from the paediatric perspective.

    Science.gov (United States)

    Roberts, Eve A

    2011-11-01

    Autoimmune hepatitis (AIH) is an important entity within the broad spectrum of autoimmune hepatobiliary disease comprised of AIH, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since the 1960s, AIH has been investigated with extensive clinical research aimed at effective therapeutic intervention. It was one of the first liver diseases where treatment was demonstrated to prolong survival. AIH occurs in children, as well as in adults. Its clinical manifestations in children may differ from classic adult AIH. These differences have elucidated certain aspects of AIH and hepatobiliary disease in general. There are two major patterns of AIH: type 1, with anti-smooth muscle antibodies and type 2, with anti-liver/kidney microsomal antibodies. The second type of AIH was first identified in children and is more common in younger patients. AIH often presents as acute disease in children and also in adults: the nomenclature has dropped the allusion to chronicity. Some children who have sclerosing cholangitis present with clinical disease closely resembling AIH; this AIH-like PSC, termed autoimmune sclerosing cholangitis (ASC), is also found in adults. Children with AIH may have identifiable monogenic disorders of immune regulation such as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Like adults with AIH, children with AIH usually respond very favourably to immunosuppressive treatment with corticosteroids ± azathioprine. True cures seem to be rare, although many children achieve a stable remission. Nonetheless children with AIH may develop cirrhosis and some require liver transplantation. Early diagnosis and improved treatment strategies may further improve the outlook for children with AIH.

  13. Electrosmog and autoimmune disease.

    Science.gov (United States)

    Marshall, Trevor G; Heil, Trudy J Rumann

    2016-07-13

    Studies in mice have shown that environmental electromagnetic waves tend to suppress the murine immune system with a potency similar to NSAIDs, yet the nature of any Electrosmog effects upon humans remains controversial. Previously, we reported how the human Vitamin-D receptor (VDR) and its ligand, 1,25-dihydroxyvitamin-D (1,25-D), are associated with many chronic inflammatory and autoimmune diseases. We have shown how olmesartan, a drug marketed for mild hypertension, acts as a high-affinity partial agonist for the VDR, and that it seems to reverse disease activity resulting from VDR dysfunction. We here report that structural instability of the activated VDR becomes apparent when observing hydrogen bond behavior with molecular dynamics, revealing that the VDR pathway exhibits a susceptibility to Electrosmog. Further, we note that characteristic modes of instability lie in the microwave frequency range, which is currently populated by cellphone and WiFi communication signals, and that the susceptibility is ligand dependent. A case series of 64 patient-reported outcomes subsequent to use of a silver-threaded cap designed to protect the brain and brain stem from microwave Electrosmog resulted in 90 % reporting "definite" or "strong" changes in their disease symptoms. This is much higher than the 3-5 % rate reported for electromagnetic hypersensitivity in a healthy population and suggests that effective control of environmental Electrosmog immunomodulation may soon become necessary for successful therapy of autoimmune disease.

  14. [Hydroxychloroquine for autoimmune diseases].

    Science.gov (United States)

    Danza, Álvaro; Graña, Diego; Goñi, Mabel; Vargas, Andrea; Ruiz-Irastorza, Guillermo

    2016-02-01

    Hydroxychloroquine (HCQ) is by far the most frequently used antimalarial for the management of Systemic Autoimmune Diseases. It has immunomodulatory, hypolipidemic, hypoglycemic and antithrombotic properties and it diminishes the risk of malignancies. The most important mechanisms to explain the immunomodulatory actions are its ability to reduce inflammatory pathways and Toll-like receptors activation. The safety profile is favorable. In spite of its low frequency, retinal toxicity is potentially severe. In systemic lupus erythematous HCQ therapy reduces activity, the accrual of organ damage, risk of infections and thrombosis and improves the cardiometabolic profile. It contributes to induce lupus nephritis remission, spares steroid use and increases survival rates. In rheumatoid arthritis, it improves cardiometabolic risk and has a favorable effect in joint inflammation. In Sjögren's syndrome, an increased lacrimal quality as well as an improvement in objective and subjective inflammatory markers has been demonstrated with HCQ. In Antiphospholipid Syndrome, HCQ is effective in primary and secondary thrombosis prevention. The effectiveness of the drug in other systemic autoimmune diseases is less established. HCQ therapy may improve dermatological manifestations in Dermatomyositis and may have a positive effects in the treatment of Sarcoidosis and Still disease.

  15. EB病毒和巨细胞病毒感染与自身免疫性肝炎Ⅰ型的关系探讨%The relationship between EB virus and cytomegalo virus infection and type I autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    刘玉宁; 徐芸; 刘智慧

    2010-01-01

    目的 探讨EB病毒(EBV)和巨细胞病毒(CMV)感染与Ⅰ型自身免疫性肝炎1型(AIH-I型)之间的关系.方法 采用酶联免疫吸附技术(ELISA)检测AIH-I型患者和对照组血清中EBV和CMV抗体IgG和IgM, CMV-IgM阳性者行聚合酶链反应(PCR)检测血清的CMV-DNA;EBV-IgM阳性者行肝组织活检免疫组织化学检测EBV抗原,再阳性者行原位杂交检测EBV特异基因,比较各对应组之间的差异.结果 在AIH-I型组和对照组之间,CMV-IgM、CMV-IgG、EBV-IgM和EBV-IgG比较差异均有统计学意义(P<0.05).AIH-I型组与对照组中CMV-IgM阳性者15例,其血清CMV-DNA均为阴性.AIH-I型组和对照组血清EBV-IgM阳性者21例,检测其肝组织中EBV抗原,阳性6例;对此6例原位杂交检测肝组织EBV基因(EBER),结果均为阴性.结论 自身免疫性肝炎患者CMV-IgG和EBV-IgG阳性率均比对照组高,推测AIH-I型患者既往感染该病毒;但IgM阳性率高于对照组并不能证明现症感染,提示IgM与自身免疫性肝炎患者某些自身抗原存在交叉免疫反应,并通过分子模拟机制诱发自身免疫性肝炎.%Objective The purpose of this study was to initially explore the relationship between the epstein-barr virus and cytomegalo virus infection and type I autoimmune hepatitis(type I AIH). Methods The IgG/IgM antibodies in EBV and CMV in serum between type I AIH group and the control group were detected by enzyme-labeled immunosorbent assay(ELISA). CMV-DNA was detected by polymerase chain reaction(PCR) in serum of CMV-IgM positive reaction. Immunohistochemistry was used to detect the EBV antigens in liver tissue which was obstained by liver biopsy.Situ hybridization was used to detect EBV -specific genes in liver tissue which also getted by liver biopsy.Then compared the differences in each other. Results Between the type I AIH group and the control group, there were significant difference in CMV-IgM, CMV-IgG, EBV-IgM and EBV-IgG (P<0.05). In the type Ⅰ AIH group and

  16. Clinical Usefulness of the Serological Gastric Biopsy for the Diagnosis of Chronic Autoimmune Gastritis

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    Antonio Antico

    2012-01-01

    Full Text Available Aim. To assess the predictive value for chronic autoimmune gastritis (AIG of the combined assay of anti-parietal-cell antibodies (PCA, anti-intrinsic-factor antibodies (IFA, anti-Helicobacter pylori (Hp antibodies, and measurement of blood gastrin. Methods. We studied 181 consecutive patients with anemia, due to iron deficiency resistant to oral replacement therapy or to vitamin B12 deficiency. Results. 83 patients (45.8% tested positive for PCA and underwent gastroscopy with multiple gastric biopsies. On the basis of the histological diagnosis, PCA-positive patients were divided into 4 groups: (1 30 patients with chronic atrophic gastritis; they had high concentrations of PCA and gastrin and no detectable IFA; (2 14 subjects with metaplastic gastric atrophy; they had high PCA, IFA, and gastrin; (3 18 patients with nonspecific lymphocytic inflammation with increased PCA, normal gastrin levels, and absence of IFA; (4 21 patients with multifocal atrophic gastritis with “borderline” PCA, normal gastrin, absence of IFA and presence of anti-Hp in 100% of the cases. Conclusions. The assay of four serological markers proved particularly effective in the diagnostic classification of gastritis and highly correlated with the histological profile. As such, this laboratory diagnostic profile may be considered an authentic “serological biopsy.”

  17. Spontaneous germinal centers and autoimmunity.

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    Domeier, Phillip P; Schell, Stephanie L; Rahman, Ziaur S M

    2017-02-01

    Germinal centers (GCs) are dynamic microenvironments that form in the secondary lymphoid organs and generate somatically mutated high-affinity antibodies necessary to establish an effective humoral immune response. Tight regulation of GC responses is critical for maintaining self-tolerance. GCs can arise in the absence of purposeful immunization or overt infection (called spontaneous GCs, Spt-GCs). In autoimmune-prone mice and patients with autoimmune disease, aberrant regulation of Spt-GCs is thought to promote the development of somatically mutated pathogenic autoantibodies and the subsequent development of autoimmunity. The mechanisms that control the formation of Spt-GCs and promote systemic autoimmune diseases remain an open question and the focus of ongoing studies. Here, we discuss the most current studies on the role of Spt-GCs in autoimmunity.

  18. Mucormycosis in systemic autoimmune diseases.

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    Royer, Mathieu; Puéchal, Xavier

    2014-07-01

    Mucormycosis is an emerging infection in systemic autoimmune diseases. All published cases of systemic autoimmune diseases complicated by mucormycosis were reviewed. The clinical features, diagnostic procedures and the main principles of treatment were analyzed. Twenty-four cases of mucormycosis have been reported in systemic auto-immune diseases, of which 83% in systemic lupus erythematosus, all occurring during immunosuppressants. In most cases, the infection was disseminated or rhinocerebral and it had mimicked a flare of the underlying connective tissue disease. A fatal outcome was reported in 58.3% of these patients. In conclusion, mucormycosis often mimics a flare of the underlying systemic disease and is associated with a high mortality rate. Systemic lupus erythematosus is by far the most common associated systemic autoimmune disease. A high degree of awareness is warranted to rapidly rule out infection, of which mucormycosis, in immunocompromised patients with systemic autoimmune disease before a disease flare is conclusively diagnosed.

  19. PTPN22: the archetypal non-HLA autoimmunity gene.

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    Stanford, Stephanie M; Bottini, Nunzio

    2014-10-01

    PTPN22 encodes a tyrosine phosphatase that is expressed by haematopoietic cells and functions as a key regulator of immune homeostasis by inhibiting T-cell receptor signalling and by selectively promoting type I interferon responses after activation of myeloid-cell pattern-recognition receptors. A single nucleotide polymorphism of PTPN22, 1858C>T (rs2476601), disrupts an interaction motif in the protein, and is the most important non-HLA genetic risk factor for rheumatoid arthritis and the second most important for juvenile idiopathic arthritis. PTPN22 exemplifies a shared autoimmunity gene, affecting the pathogenesis of systemic lupus erythematosus, vasculitis and other autoimmune diseases. In this Review, we explore the role of PTPN22 in autoimmune connective tissue disease, with particular emphasis on candidate-gene and genome-wide association studies and clinical variability of disease. We also propose a number of PTPN22-dependent functional models of the pathogenesis of autoimmune diseases.

  20. Autoimmune regulator and self-tolerance - molecular and clinical aspects.

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    Abramson, Jakub; Husebye, Eystein S

    2016-05-01

    The establishment of central tolerance in the thymus is critical for avoiding deleterious autoimmune diseases. Autoimmune regulator (AIRE), the causative gene in autoimmune polyendocrine syndrome type-1 (APS-1), is crucial for the establishment of self-tolerance in the thymus by promoting promiscuous expression of a wide array of tissue-restricted self-antigens. This step is critical for elimination of high-affinity self-reactive T cells from the immunological repertoire, and for the induction of a specific subset of Foxp3(+) T-regulatory (Treg ) cells. In this review, we discuss the most recent advances in our understanding of how AIRE operates on molecular and cellular levels, as well as of how its loss of function results in breakdown of self-tolerance mechanisms characterized by a broad and heterogeneous repertoire of autoimmune phenotypes.

  1. Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer.

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    Juozas Kupcinskas

    Full Text Available BACKGROUND AND AIMS: MicroRNAs (miRNAs are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 and the presence of GC or high risk atrophic gastritis (HRAG in European population. METHODS: Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281 of European descent. MiR-27a T>C (rs895819, miR-146a G>C (rs2910164, miR-196a-2 C>T (rs11614913, miR-492 G>C (rs2289030 and miR-608 C>G (rs4919510 SNPs were genotyped by RT-PCR. RESULTS: Overall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR - 1.46, 95% confidence interval (CI 1.03-2.07, P = 0.032. MiR-608 GG genotype was more frequent in GC when compared to controls (OR -2.34, 95% CI 1.08-5.04, but significance remained marginal (P = 0.029. A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14-5.22, P = 0.021. The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC. CONCLUSIONS: Gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European

  2. Efficacy of fractional CO2 laser in treatment of atrophic scar of cutaneous leishmaniasis.

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    Banihashemi, Mahnaz; Nahidi, Yalda; Maleki, Masoud; Esmaily, Habibollah; Moghimi, Hamid Reza

    2016-05-01

    Cutaneous leishmaniasis is an endemic disease in Iran. Unfortunately, it can lead to unsightly atrophic scars with limited treatment options. Fractional CO2 laser is accepted for treatment of atrophic acne scars and recently has been used to treat cutaneous leishmaniasis, so we planned to use fractional CO2 laser on leishmaniasis scar. We conducted this study on 60 leishmaniasis scars on the face of 40 patients. The lesions were treated by a fractional CO2 laser with beam size of 120 μm, with energy of 50-90 mJ, and 50-100 spots/cm(2) density with two passes in three monthly sessions. Evaluation was done in the first and second months after the first treatment and 3 and 6 months after the last treatment. Digital photography was performed at each visit. Assessment of improvement rate by patient and physician was rated separately as follows: no improvement (0%), mild (CO2 laser for leishmaniasis scar. No significant adverse effects were noted.

  3. Detection and characterization of stomach cancer and atrophic gastritis with fluorescence and Raman spectroscopy

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    Li, Xiaozhou; Lin, Junxiu; Jia, Chunde; Wang, Rong

    2003-12-01

    In this paper, we attempt to find a valid method to distinguish gastric cancer and atrophic gastritis. Auto-fluorescence and Raman spectroscopy of laser induced (514.5 nm and 488.0 nm) was measured. The serum spectrum is different between normal and cancer. Average value of diagnosis parameter for normal serum, red shift is less than 12 nm and Raman relative intensity of peak C by 514.5 nm excited is stronger than that of 488.0 nm. To gastric cancer, its red shift of average is bigger than 12 nm and relative intensity of Raman peak C by 514.5 nm excited is weaker than that by 488.0 nm. To atrophic gastritis, the distribution state of Raman peaks is similar with normal serum and auto-fluorescence spectrum's shape is similar to that of gastric cancer. Its average Raman peak red shift is bigger than 12 nm and the relative intensity of peak C by 514.5 excited is stronger than that of by 488.0. We considered it as a criterion and got an accuracy of 85.6% for diagnosis of gastric cancer compared with the result of clinical diagnosis.

  4. Prevalence of chronic atrophic gastritis in different parts of the world.

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    Weck, Melanie Nicole; Brenner, Hermann

    2006-06-01

    Chronic atrophic gastritis (CAG) is a well-established precursor of intestinal gastric cancer, but epidemiologic data about its occurrence are sparse. We provide an overview on studies that examined the prevalence of CAG in different parts of the world. Articles containing data about the prevalence of chronic atrophic gastritis in unselected population samples and published until November 2005 were identified by searching the MEDLINE database. Furthermore, the references in the identified publications were screened for additional suitable studies. Studies comprising at least 50 subjects were included. Forty-one studies providing data on the prevalence of CAG in unselected population samples could be identified. CAG was determined by gastroscopy in 15 studies and by pepsinogen serum levels in 26 studies. Although results are difficult to compare due to the various definitions of CAG used, a strong increase with age, the lack of major gender differences, and strong variations between populations and population groups (in particular, relatively high rates in certain Asian populations) could be observed quite consistently. We conclude that CAG is relatively common among older adults in different parts of the world, but large variations exist. Large-scale international comparative studies with standardized methodology to determine CAG are needed to provide a coherent picture of the epidemiology of CAG in various populations. Noninvasive measurements of CAG by pepsinogen levels may be particularly suited for that purpose.

  5. Progressive atrophic rhinitis in a medium-scale pig farm in Kiambu, Kenya : case report

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    J.K. Wabacha

    2000-07-01

    Full Text Available Forty-two pigs in a herd of 117 displayed various clinical signs of progressive atrophic rhinitis. The main signs included sneezing, coughing, lachrymation, serous to muco-purulent nasal discharge, and nasal bleeding in 1 pig. Three pigs had lateral deviation of the snout, while 4 had brachygnathia superior with obvious deformation of the face. Four acutely affected weaner pigs appeared weak, while the 7 chronically-affected pigs appeared smaller than their apparently unaffected penmates of the same age. Treatment of the acutely affected pigs with long-acting oxytetracycline at 20 mg/kg body weight intra-muscularly, repeated once after 7 days, reduced the severity but did not clear the sneezing from all the pigs. Fifteen pigs were slaughtered 2 months after the clinical diagnosis was made. The carcasses of the chronically affected pigs were about 15 % lighter than those of the apparently normal pigs of the same age and from the same pen, which translated to a loss of 921.00 Kenya shillings per pig (US$13.7. Diagnosis of progressive atrophic rhinitis was confirmed by sectioning the snouts of randomly selected slaughtered pigs with obvious deformation of the snout. Sections were madeat the level of the 1st/2nd upper premolar tooth. Varying degrees of turbinate atrophy, from mild to complete, were noted. Histopathology of the turbinates revealed metaplasia of nasal epithelium and fibrosis in the lamina propria.

  6. Probiotics for the prevention of beta cell autoimmunity in children at genetic risk of type 1 diabetes--the PRODIA study.

    Science.gov (United States)

    Ljungberg, Martin; Korpela, Riita; Ilonen, Jorma; Ludvigsson, Johnny; Vaarala, Outi

    2006-10-01

    The final aim of the PRODIA study is to determine whether the use of probiotics during the first 6 months of life decreases the appearance of type 1 diabetes mellitus (T1DM)-associated autoantibodies in children with genetic risk for T1DM. A pilot study including 200 subjects was planned to show whether the use of probiotics during the first 6 months of life is safe and feasible. The prevalence of autoantibodies among the study subjects at 6, 12, and 24 months of age was at levels close to the expected and the clinical follow-up did not either indicate problems in the feasibility of the study.

  7. [Autoimmune hemolytic anemia: diagnosis and management].

    Science.gov (United States)

    Philippe, Pierre

    2007-12-01

    Autoimmune hemolytic anemia (AIHA) is diagnosed in the presence of anemia, usually macrocytic and of variable intensity, reticulocytosis, and a positive direct and/or indirect antiglobulin test, after ruling out other types of hemolytic anemia. A positive direct antiglobulin test alone is not sufficient to diagnose AIHA and may be positive in many patients without anemia or negative in some patients with AIHA. AIHA may be classified into two major categories according to the optimal temperature of antibody activity: warm-reacting autoantibodies (usually IgG) optimal around 37 degrees C and cold-reacting autoantibodies, optimal at 4 degrees C (usually IgM). This classification guides the selection of tests and treatment. AIHA is widely reported to be associated with a variety of other diseases, although these associations are often fortuitous. A minimal set of useful investigations is appropriate since AIHA may be secondary to viral infections, lymphoid malignancies, or autoimmune disorders such as lupus. Transfusion should remain rare in AHAI, but close contact with the transfusion service is necessary if it is to succeed. As for many autoimmune and/or systemic diseases, numerous types of treatment have been proposed but have not been validated in controlled multicenter studies. These are necessary to improve the management of these rare disorders.

  8. The expression of the beta cell-derived autoimmune ligand for the killer receptor nkp46 is attenuated in type 2 diabetes.

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    Chamutal Gur

    Full Text Available NK cells rapidly kill tumor cells, virus infected cells and even self cells. This is mediated via killer receptors, among which NKp46 (NCR1 in mice is prominent. We have recently demonstrated that in type 1 diabetes (T1D NK cells accumulate in the diseased pancreas and that they manifest a hyporesponsive phenotype. In addition, we found that NKp46 recognizes an unknown ligand expressed by beta cells derived from humans and mice and that blocking of NKp46 activity prevented diabetes development. Here we investigated the properties of the unknown NKp46 ligand. We show that the NKp46 ligand is mainly located in insulin granules and that it is constitutively secreted. Following glucose stimulation the NKp46 ligand translocates to the cell membrane and its secretion decreases. We further demonstrate by using several modalities that the unknown NKp46 ligand is not insulin. Finally, we studied the expression of the NKp46 ligand in type 2 diabetes (T2D using 3 different in vivo models and 2 species; mice and gerbils. We demonstrate that the expression of the NKp46 ligand is decreased in all models of T2D studied, suggesting that NKp46 is not involved in T2D.

  9. Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

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    Stefan Vordenbäumen

    2011-08-01

    Full Text Available Defensins are small cationic peptides with antimicrobial properties. They constitute a highly conserved innate immune defense mechanism across species. Based on the arrangement of disulfide-bonds, α- and β-defensins are distinguished in humans. Both types of defensin comprise several distinct molecules that are preferentially expressed at epithelial surfaces and in blood cells. In the last decade, multiple immunomodulatory functions of defensins have been recognized, including chemotactic activity, the promotion of antigen presentation, and modulations of proinflammatory cytokine secretion. These findings suggested a role for defensins not only as a first line of defense, but also as connectors of innate and adaptive immune responses. Recently, increasingly accumulating evidence has indicated that defensins may also be involved in the pathogenesis of autoimmune rheumatic disorders such as systemic lupus erythematosus and rheumatoid arthritis. The current review summarizes the data connecting defensins to autoimmunity.

  10. The autoimmune tautology: an in silico approach.

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    Cifuentes, Ricardo A; Restrepo-Montoya, Daniel; Anaya, Juan-Manuel

    2012-01-01

    There is genetic evidence of similarities and differences among autoimmune diseases (AIDs) that warrants looking at a general panorama of what has been published. Thus, our aim was to determine the main shared genes and to what extent they contribute to building clusters of AIDs. We combined a text-mining approach to build clusters of genetic concept profiles (GCPs) from the literature in MedLine with knowledge of protein-protein interactions to confirm if genes in GCP encode proteins that truly interact. We found three clusters in which the genes with the highest contribution encoded proteins that showed strong and specific interactions. After projecting the AIDs on a plane, two clusters could be discerned: Sjögren's syndrome-systemic lupus erythematosus, and autoimmune thyroid disease-type1 diabetes-rheumatoid arthritis. Our results support the common origin of AIDs and the role of genes involved in apoptosis such as CTLA4, FASLG, and IL10.

  11. A comparative study of toluidine blue-mediated photodynamic therapy versus topical corticosteroids in the treatment of erosive-atrophic oral lichen planus: a randomized clinical controlled trial.

    Science.gov (United States)

    Jajarm, Hasan Hoseinpour; Falaki, Farnaz; Sanatkhani, Majid; Ahmadzadeh, Meysam; Ahrari, Farzaneh; Shafaee, Hooman

    2015-07-01

    Recently, photodynamic therapy (PDT) has been suggested as a new treatment option that is free from side effects for erosive-atrophic oral lichen planus (OLP). The purpose of this study was to compare the effect of toluidine blue-mediated photodynamic therapy (TB-PDT) with local corticosteroids on treatment of erosive-atrophic OLP. In this randomized clinical trial, 25 patients with keratotic-atrophic-erosive oral lichen planus were allocated randomly into two groups. Group 1 (experimental): topical application of toluidine blue with micropipette was applied, and after 10 min, the patients were treated with a 630-nm GaAlAs laser (power density: 10 mW/cm(2)) during two visits. Group 2 (control) used mouthwash diluted with dexamethasone (tab 0/5 in 5 ml water) for 5 min, and then, it was spat out, and after 30 min, the mouth was rinsed with 30 drops of nystatin 100,000 units for 5 min and again spat out. Demographic data, type, and severity of the lesions and pain were recorded before and after treatment and then at the 1-month follow-up visit. Response rate was defined based on changes in intensity of the lesions and pain. In the experimental and control groups, sign scores of changes significantly reduced after treatment respectively (p = 0.021) and (p = 0.002), but between the two groups, no significant difference was observed (p = 0.72). In the experimental (p = 0.005) and control groups (p = 0.001), the intensity of lesions significantly reduced after treatment and there was a significant difference between the two groups (p = 0.001). The mean amount of improvement in pain was significantly greater in the control group compared with the experimental group (p < 0.001) (α = 0.05). Our study showed that TB-PDT with laser was effective in the management of OLP.

  12. Endocrine autoimmunity in Turner syndrome

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    2013-01-01

    Background Turner syndrome is caused by numeric and structural abnormalities of the X chromosome. An increased frequency of autoimmunity as well as an elevated incidence of autoantibodies was observed in Turner patients. The aim of this study was to conduct a retrospective analysis of the incidence of autoimmunity in 66 Italian patients affected by Turner syndrome. Methods Sixty-six unselected and consecutive Italian Turner patients were recruited. The association between age, karyotype and the presence of clinical/pre-clinical autoimmune disorders and of autoantibodies was examined. Results Out of the 66 Turner patients, 26 had thyroid autoimmune disorders (39.4%), 14 patients had Hashimoto’s thyroiditis with clinical or subclinical hypothyroidism (21.2%) and 12 patients had circulating anti-thyroid antibodies, echographic pattern of diffuse hypoechogenicity and normal thyroid hormone levels (18.2%). None were affected by Graves’ disease. We analyzed the overall incidence of thyroid autoimmunity within the 3 different age groups 0–9.9, 10–19.9 and 20–29.9 years. No statistically significant difference was observed in the incidence of thyroid autoimmunity within the age-groups (χ2-test p > 0.05). Out of the 66 patients, 31 patients had the 45,X karyotype; within this first group 14 out of 31 patients were affected by autoimmune thyroid disease. A second group of 29 patients included 19 patients with mosaicism, 5 patients with deletions and 5 patients with ring chromosome; out of these 29 patients 7 were affected by autoimmune thyroid disease. A third group included 6 patients with X isochromosome; 5 out of 6 were affected by autoimmune thyroid disease. A statistically significant difference in the frequency of thyroid autoimmunity within the different karyotype groups was observed (χ2-test p = 0.0173). When comparing the X isochromosome group with the pooled group of other karyotypes, of note, the frequency of thyroid autoimmunity was

  13. Recent Advances in Autoimmune Pancreatitis.

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    Hart, Phil A; Zen, Yoh; Chari, Suresh T

    2015-07-01

    Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that is characterized clinically by frequent presentation with obstructive jaundice, histologically by a dense lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response to corticosteroid therapy. Two distinct diseases, type 1 and type 2 AIP, share these features. However, these 2 diseases have unique pancreatic histopathologic patterns and differ significantly in their demographic profiles, clinical presentation, and natural history. Recognizing the popular and long-standing association of the term "AIP" with what is now called "type 1 AIP," we suggest using "AIP" solely for type 1 AIP and to acknowledge its own distinct disease status by using "idiopathic duct-centric chronic pancreatitis" (IDCP) for type 2 AIP. AIP is the pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). The etiopathogenesis of AIP and IgG4-RD is largely unknown. However, the remarkable effectiveness of B-cell depletion therapy with rituximab in patients with AIP and IgG4-RD highlights the crucial role of B cells in its pathogenesis. IDCP is less commonly recognized, and little is known about its pathogenesis. IDCP has no biomarker but is associated with inflammatory bowel disease in ~25% of patients. Recently, the international consensus diagnostic criteria for AIP identified combinations of features that are diagnostic of both diseases. Both AIP and IDCP are corticosteroid responsive; however, relapses are common in AIP and rare in IDCP. Therefore, maintenance therapy with either an immunomodulator (eg, azathioprine, 6-mercaptopurine, or mycophenolate mofetil) or rituximab is often necessary for patients with AIP. Long-term survival is excellent for both patients with AIP and patients with IDCP.

  14. SOCS, inflammation and autoimmunity

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    Akihiko eYoshimura

    2012-03-01

    Full Text Available Cytokines play essential roles in innate and adaptive immunity. However, excess cytokines or dysregulation of cytokine signaling can cause a variety of diseases, including allergies, autoimmune diseases, inflammation, and cancer. Most cytokines utilize the so-called Janus kinase-signal transducers and activators of transcription (JAK-STAT pathway. This pathway is negatively regulated by various mechanisms including suppressors of cytokine signaling (SOCS proteins. SOCS proteins bind to JAK or cytokine receptors, thereby suppressing further signaling events. Especially, SOCS1 and SOCS3 are strong inhibitors of JAK, because these two contain kinase inhibitory region (KIR at the N-terminus. Studies using conditional knockout mice have shown that SOCS proteins are key physiological as well as pathological regulators of immune homeostasis. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of helper T cell differentiation and functions.

  15. Adult autoimmune enteropathy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before treatment, but these are not altered by any form of dietary restriction, including a gluten-free diet. As in celiac disease, histologic changes in gastric and colonic biopsies have also been recorded. Anti enterocyte antibodies detected with immunofluorescent methods have been reported by a few laboratories, but these antibodies appear not to be specific and may simply represent epiphenomena. A widely available, reproducible and quantitative anti-enterocyte antibody assay is needed that could be applied in small bowel disorders that have the histological appearance of celiac disease, but fail to respond to a gluten-free diet.

  16. Psychoneuroimmunology - psyche and autoimmunity.

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    Ziemssen, Tjalf

    2012-01-01

    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.

  17. Pathophysiology of autoimmune polyneuropathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2013-06-01

    The most common autoimmune neuropathies include the acute inflammatory polyneuropathy [the Guillain-Barré Syndrome(s)]; chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN) and IgM anti-MAG-antibody mediated paraproteinemic neuropathy. These neuropathies occur when immunologic tolerance to peripheral nerve components (myelin, Schwann cell, axon, and motor or ganglionic neurons) is lost. Based on the immunopathologic similarities with experimental allergic neuritis induced after immunization with nerve proteins, disease transfer experiments with the patients' serum or with intraneural injections, and immunocytochemical studies on the patients' nerves, it appears that both cellular and humoral factors, either independently or in concert with each other, play a role in the cause of these neuropathies. Although in some of them there is direct evidence for autoimmune reactivity mediated by specific antibodies or autoreactive T lymphocytes, in others the underlying immune-mediated mechanisms have not been fully elucidated, in spite of good response to immunotherapies. The review highlights the factors associated with breaking the T-cell tolerance, the T-cell activation and costimulatory molecules, the immunoregulatory T-cells and relevant cytokines and the antibodies against peripheral nerve glycolipids or glycoproteins that seem to be of pathogenic relevance. Antigens in the nodal, paranodal and juxtaparanodal regions are discussed as potentially critical targets in explaining conduction failure and rapid recovery. Based on the immunopathologic network believed to play a fundamental role in the pathogenesis of these neuropathies, future therapeutic directions are highlighted using new biological agents against T-cells, cytokines, B-cells, transmigration and transduction molecules.

  18. Development of autoimmunity in lymphoma.

    Science.gov (United States)

    Jardin, Fabrice

    2008-03-01

    Development of lymphoproliferative diseases during the course of autoimmune and chronic inflammatory conditions is well established. Conversely, development of clinical or biological signs of autoimmunity at the time of the diagnosis of lymphoma or during its course indicates that lymphoma and autoimmune manifestations may constitute two faces of the same process. The aim of this review is to describe autoimmune manifestations related to non-Hodgkin's lymphoma and Hodgkin's lymphoma, their specificity according to the lymphoma subtype and their physiopathological signification. Lymphoma-related autoimmune manifestations include mainly skin diseases, hematological manifestations, rheumatic diseases and renal lesions. Despite the lack of studies providing a systematic prospective assessment, autoimmune manifestations are observed in all lymphoma subtypes and seem particularly prevalent in marginal-zone lymphoma and T-cell lymphoma. Autoimmune manifestation's physiopathology may implicate production of autoantibodies by CD5-positive autoreactive B cells, a loss of immune tolerance, an alteration of the Fas/Fas-ligand pathway and/or a chronic antigenic stimulation. Monoclonal antibodies (including rituximab, Campath-1H or epratuzumab) constitute the most promising approach to treat lymphoma-related immune disorders.

  19. Finite element analysis of dental implant loading on atrophic and non-atrophic cancellous and cortical mandibular bone - a feasibility study.

    Science.gov (United States)

    Marcián, Petr; Borák, Libor; Valášek, Jiří; Kaiser, Jozef; Florian, Zdeněk; Wolff, Jan

    2014-12-18

    The first aim of this study was to assess displacements and micro-strain induced on different grades of atrophic cortical and trabecular mandibular bone by axially loaded dental implants using finite element analysis (FEA). The second aim was to assess the micro-strain induced by different implant geometries and the levels of bone-to-implant contact (BIC) on the surrounding bone. Six mandibular bone segments demonstrating different grades of mandibular bone atrophy and various bone volume fractions (from 0.149 to 0.471) were imaged using a micro-CT device. The acquired bone STL models and implant (Brånemark, Straumann, Ankylos) were merged into a three-dimensional finite elements structure. The mean displacement value for all implants was 3.1 ±1.2 µm. Displacements were lower in the group with a strong BIC. The results indicated that the maximum strain values of cortical and cancellous bone increased with lower bone density. Strain distribution is the first and foremost dependent on the shape of bone and architecture of cancellous bone. The geometry of the implant, thread patterns, grade of bone atrophy and BIC all affect the displacement and micro-strain on the mandible bone. Preoperative finite element analysis could offer improved predictability in the long-term outlook of dental implant restorations.

  20. Autoimmune hepatitis: a classic autoimmune liver disease.

    Science.gov (United States)

    Moy, Libia; Levine, Jeremiah

    2014-12-01

    AIH is characterized by chronic inflammation of the liver, interface hepatitis, hypergammaglobulinemia, and production of autoantibodies. Based on the nature of the serum autoantibodies, two types of AIH are recognized: type 1 (AIH-1), positive for ANA and/or anti-smooth muscle antibody, and type 2 (AIH-2), defined by the positivity for anti-liver kidney microsomal type 1 antibody or for anti-liver cytosol type 1 antibody. AIH demonstrates a female preponderance with the female-to-male ratio of 4:1 in AIH-1 and 10:1 in AIH-2. Several genes confer susceptibility to AIH and influence clinical manifestation, response to treatment, and overall prognosis. Most are located within the human leukocyte antigen (HLA) region, which is involved in the presentation of antigenic peptides to T cells and thus in the initiation of adaptive immune responses. The strongest associations are found within the HLA-DRB1 locus. In patients with increased genetic susceptibility to AIH, immune responses to liver autoantigens could be triggered by molecular mimicry. Because of molecular mimicry, different environmental agents, drugs, and viruses might produce AIH. In AIH, T cells are numerically and functionally impaired, permitting the perpetuation of effector immune responses with ensuing persistent liver destruction. AIH is rare but highly treatable inflammatory condition of the liver. Subclinical and asymptomatic disease is common. AIH therefore needs to be considered in the differential diagnosis of all patients with elevated liver enzymes. Clinical response to immunosuppressive therapy is characteristic and supports the diagnosis.

  1. Prevalence and epidemiology of autoimmune hepatitis.

    Science.gov (United States)

    Boberg, Kirsten Muri

    2002-08-01

    The incidence and characteristics of AIH differ in various geographic regions. Based on limited epidemiologic studies, the incidence of type 1 AIH among Caucasoid populations of Europe and North America ranges from 0.1 to 1.9/100,000/year. The disease is considerably less frequent in Japan. The relative proportion of AIH among cases with chronic hepatitis is low in regions with a high prevalence of viral hepatitis. Type 2 AIH is more frequent in southern Europe than in northern Europe, the United States, and Japan. The occurrence of anti-SLA/LP is also higher in European than in Japanese patients with type 1 AIH. The frequency of HLA markers that affect susceptibility to AIH varies between ethnic groups. DRB1*0301 (DR3) and DRB1*0401 (DR4) are the major risk factors for type 1 AIH in white European and North American populations. DRB1*0405 (DR4) is the principal risk factor in Japanese and adult Argentine patients with type 1 AIH, and DRB1*0404 (DR4) is the main susceptibility allele in Mestizo Mexicans. Children may have different clinical manifestations than adults, and the diagnoses of type 2 AIH, autoimmune sclerosing cholangitis, and APS1 should be considered. Uniform application of diagnostic criteria formulated by the International Autoimmune Hepatitis Group should strengthen future epidemiologic studies and extend awareness of AIH to yet unstudied minority groups.

  2. Questions and Answers on Autoimmunity and Autoimmune Diseases

    Science.gov (United States)

    ... Autoimmune Coalition Your Privacy Get Involved Donate Grassroots Fundraising ? Advocate for Change Take our Survey Information List ... Common Thread Coping Tools InFocus Newsletter Questions & Answers Fundraising Grassroots Fundraising Workplace Giving Special Events AARDA on ...

  3. Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity

    Directory of Open Access Journals (Sweden)

    Manfred Kunz

    2009-01-01

    Full Text Available The precise pathomechanisms of human autoimmune diseases are still poorly understood. However, a deepened understanding of these is urgently needed to improve disease prevention and early detection and guide more specific treatment approaches. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been detected. Major contributions were made by experiments using DNA microarray technology, which has been used for the analysis of gene expression patterns in chronic inflammatory and autoimmune diseases, among which were rheumatoid arthritis, systemic lupus erythematosus, psoriasis, systemic sclerosis, multiple sclerosis, and type-1 diabetes. In systemic lupus erythematosus, a so-called interferon signature has been identified. In psoriasis, researchers found a particular immune signalling cluster. Moreover the identification of a new subset of inflammatory T cells, so-called Th17 T cells, secreting interleukin (IL-17 as one of their major cytokines and the identification of the IL-23/IL-17 axis of inflammation regulation, have significantly improved our understanding of autoimmune diseases. Since a plethora of new treatment approaches using antibodies or small molecule inhibitors specifically targeting cytokines, cellular receptors, or signalling mechanisms has emerged in recent years, more individualized treatment for affected patients may be within reach in the future.

  4. Epigenetic control of autoimmune diseases: from bench to bedside.

    Science.gov (United States)

    Picascia, Antonietta; Grimaldi, Vincenzo; Pignalosa, Orlando; De Pascale, Maria Rosaria; Schiano, Concetta; Napoli, Claudio

    2015-03-01

    Genome-wide association studies have revealed several genes predisposing to autoimmunity, however, concordance rates in monozygotic twins are significantly below 50% for several autoimmune diseases. The limited presence of a strong genetic association only in some patients supports that other non-genetic mechanisms are active in these pathologies. Epigenetic modifications such as DNA methylation, histone modification, and microRNA signaling regulate gene expression and are sensitive to external stimuli and they might be as bridging between genetic and environmental factors. Some evidence has highlighted the involvement of epigenetic alterations in the pathogenesis of various autoimmune diseases giving rise to great expectations among clinicians and researchers. The direct role of these alterations in the initiation/progression of autoimmune diseases is still unclear. The knowledge in depth of these pathogenic and epigenetic mechanisms will increase the possibility of the control and/or prevention of autoimmune diseases through the use of drugs that target epigenetic pathways. Moreover, we could use epigenetic-related biomarkers to follow this complicated framework (for example H3K4me3 and miRNA-155 are among those proposed biomarkers). This article reviews current understanding of the epigenetic involvement in the field of autoimmune diseases especially in systemic lupus erythematosus, rheumatoid arthritis, sclerosis multiple and type 1 diabetes.

  5. Targeting Dendritic Cell Function during Systemic Autoimmunity to Restore Tolerance

    Directory of Open Access Journals (Sweden)

    Juan P. Mackern-Oberti

    2014-09-01

    Full Text Available Systemic autoimmune diseases can damage nearly every tissue or cell type of the body. Although a great deal of progress has been made in understanding the pathogenesis of autoimmune diseases, current therapies have not been improved, remain unspecific and are associated with significant side effects. Because dendritic cells (DCs play a major role in promoting immune tolerance against self-antigens (self-Ags, current efforts are focusing at generating new therapies based on the transfer of tolerogenic DCs (tolDCs during autoimmunity. However, the feasibility of this approach during systemic autoimmunity has yet to be evaluated. TolDCs may ameliorate autoimmunity mainly by restoring T cell tolerance and, thus, indirectly modulating autoantibody development. In vitro induction of tolDCs loaded with immunodominant self-Ags and subsequent cell transfer to patients would be a specific new therapy that will avoid systemic immunosuppression. Herein, we review recent approaches evaluating the potential of tolDCs for the treatment of systemic autoimmune disorders.

  6. Hydrolyzed infant formula and early β-cell autoimmunity

    DEFF Research Database (Denmark)

    Knip, Mikael; Åkerblom, Hans K; Becker, Dorothy

    2014-01-01

    IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain ...

  7. Autoimmune disease classification by inverse association with SNP alleles.

    Directory of Open Access Journals (Sweden)

    Marina Sirota

    2009-12-01

    Full Text Available With multiple genome-wide association studies (GWAS performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction of allele-specific disease associations for SNPs. In this work, we refine the notion of a genetic variation profile for a given disease to capture strength of association with multiple SNPs in an allele-specific fashion. We apply this method to compare genetic variation profiles of six autoimmune diseases: multiple sclerosis (MS, ankylosing spondylitis (AS, autoimmune thyroid disease (ATD, rheumatoid arthritis (RA, Crohn's disease (CD, and type 1 diabetes (T1D, as well as five non-autoimmune diseases. We quantify pair-wise relationships between these diseases and find two broad clusters of autoimmune disease where SNPs that make an individual susceptible to one class of autoimmune disease also protect from diseases in the other autoimmune class. We find that RA and AS form one such class, and MS and ATD another. We identify specific SNPs and genes with opposite risk profiles for these two classes. We furthermore explore individual SNPs that play an important role in defining similarities and differences between disease pairs. We present a novel, systematic, cross-platform approach to identify allele-specific relationships between disease pairs based on genetic variation as well as the individual SNPs which drive the relationships. While recognizing similarities between diseases might lead to identifying novel treatment options, detecting differences between diseases previously thought to be similar may point to key novel disease-specific genes and pathways.

  8. Efficacy of punch elevation combined with fractional carbon dioxide laser resurfacing in facial atrophic acne scarring: A randomized split-face clinical study

    Directory of Open Access Journals (Sweden)

    Gita Faghihi

    2015-01-01

    Full Text Available Background: A number of treatments for reducing the appearance of acne scars are available, but general guidelines for optimizing acne scar treatment do not exist. The aim of this study was to compare the clinical effectiveness and side effects of fractional carbon dioxide (CO 2 laser resurfacing combined with punch elevation with fractional CO 2 laser resurfacing alone in the treatment of atrophic acne scars. Materials and Methods: Forty-two Iranian subjects (age range 18-55 with Fitzpatrick skin types III to IV and moderate to severe atrophic acne scars on both cheeks received randomized split-face treatments: One side received fractional CO 2 laser treatment and the other received one session of punch elevation combined with two sessions of laser fractional CO 2 laser treatment, separated by an interval of 1 month. Two dermatologists independently evaluated improvement in acne scars 4 and 16 weeks after the last treatment. Side effects were also recorded after each treatment. Results: The mean ± SD age of patients was 23.4 ± 2.6 years. Clinical improvement of facial acne scarring was assessed by two dermatologists blinded to treatment conditions. No significant difference in evaluation was observed 1 month after treatment (P = 0.56. Their evaluation found that fractional CO 2 laser treatment combined with punch elevation had greater efficacy than that with fractional CO 2 laser treatment alone, assessed 4 months after treatment (P = 0.02. Among all side effects, coagulated crust formation and pruritus at day 3 after fractional CO 2 laser treatment was significant on both treatment sides (P < 0.05. Conclusion: Concurrent use of fractional laser skin resurfacing with punch elevation offers a safe and effective approach for the treatment of acne scarring.

  9. [Autoimmune pancreatitis as an element of autoimmune polyglandular syndrome].

    Science.gov (United States)

    Dyrla, Przemysław; Nowak, Tomasz; Gil, Jerzy; Adamiec, Cezary; Bobula, Mariusz; Saracyn, Marek

    2016-05-01

    Autoimmune pancreatitis constantly belongs to diseases which often causes significant diagnostic problem and often runs out with surgical intervention as considered to be a pancreatic cancer. Important although usually underestimated problems are polyglandular syndromes, which may consist of autoimmune pancreatitis (AIP) problem as well. This case report is an example of autoimmune polyglandular syndrome (APS), which was connected with the surgical treatment with biliary bypass anastomosis because of the unresectable lesion in the head of pancreas. The definite remission of the pancreatic lesion finally came after a steroid therapy. Differentiation between neoplastic and inflammatory pancreatic tumors very often remains a serious clinical problem. On grounds of imaging and cytopathology exams it is often difficult to decide about the nature of a lesion. The negative result of cytopathological biopsy examination does not finally settle straightforward diagnosis. Diagnostic problems affect also autoimmune pancreatitis. It is worth to undertake attempts to differentiate pancreatic lesions especially in cases of concomitance with other autoimmune polyglandular syndromes. That is because it is connected with completely different treatment and outcome. We should remember about diagnostic criteria of autoimmune pancreatitis. Appropriate diagnosis for patients with AIP gives them a chance to avoid serious surgical resection and possible complications.

  10. What is the quality of the evidence base for pre-implant surgery of the atrophic jaw?

    NARCIS (Netherlands)

    Blackburn, T.K.; Cawood, J.I.; Stoelinga, P.J.W.; Lowe, D.

    2008-01-01

    This review aimed to evaluate the level of evidence for bone augmentation preimplant surgery for atrophic jaws in studies which measure outcome. Medline, Embase, Cochrane library and online journal searches were performed with a defined search strategy and the abstracts screened against selection cr

  11. Stem cell therapy for severe autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Marmont Alberto M.

    2002-01-01

    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.

  12. Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia

    Directory of Open Access Journals (Sweden)

    Bainan Liu

    2013-01-01

    Full Text Available Warm autoimmune hemolytic anemia (WAIHA is one of four clinical types of autoimmune hemolytic anemia (AIHA, with the characteristics of autoantibodies maximally active at body temperature. It produces a variable anemia—sometimes mild and sometimes severe. With respect to the absence or presence of an underlying condition, WAIHA is either idiopathic (primary or secondary, which determines the treatment strategies in practice. Conventional treatments include immune suppression with corticosteroids and, in some cases, splenectomy. In recent years, the number of clinical studies with monoclonal antibodies and immunosuppressants in the treatment of WAIHA increased as the knowledge of autoimmunity mechanisms extended. This thread of developing new tools of treating WAIHA is well exemplified with the success in using anti-CD20 monoclonal antibody, Rituximab. Following this success, other treatment methods based on the immune mechanisms of WAIHA have emerged. We reviewed these newly developed immunotherapy treatments here in order to provide the clinicians with more options in selecting the best therapy for patients with WAIHA, hoping to stimulate researchers to find more novel immunotherapy strategies.

  13. AUTOIMMUNE HEMOLYTIC ANAEMIA IN CHILDHOOD: CASE REPORT

    Directory of Open Access Journals (Sweden)

    Preeti

    2015-06-01

    Full Text Available The hemolytic anemia brought about by autoimmune antibodies against red cells resulting in shortening of red cell survival. And excessive erythropoiesis as a compensatory response of the marrow is autoimmune hemolytic anemia. There are two types due to wa rm antibodies and cold antibodies. Warm antibodies mediated anemia has hemolysis in spleen mediated by IgG antibody. Macrophage Fc receptor can detect IgG coated red cells in absence of C 3b. It acts in the range of 37 - 42deg c. (1 Cold antibody mediated anemia is mediated by IgM antibody, they bind avidly at 4 deg c. carry hemolysis at low temp. Liver is the major site of hemolysis. Autoimmune hemolytic anemia presents as sudden onset of pallor, jaundice, dark coloured urine, and he pato splenomegaly. In 5 cases cold antibodies were positive, 3 cases warm were positive too. 4 of the 5 cases were females and steroids were effective in management of cold auto immune hemolytic anemia.

  14. The influence of pregnancy on the development of autoimmunity in chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Jønsson, Viggo; Bock, Johannes E; Hilden, Jørgen;

    2006-01-01

    additional sexual partner (the odds of autoimmunity increased 11 times with each long-term sexual partner). The average numbers of pregnancies in female CLL patients with and without autoimmunity were 4.92 and 2.24, respectively (P anemia, a gastric ulcer with parietal......To examine whether pregnancy influences the development of autoimmunity in chronic lymphocytic leukemia (CLL), we studied 591 consecutive CLL patients (202 post-menopausal women and 389 men). The mean observation time for all patients was 3.8 years, corresponding to approximately 2200 person....... In female CLL patients, the frequency of autoimmunity and the number of pregnancies and the number of partners were strongly correlated. Each of the major autoimmune types approximately doubled in frequency for each additional pregnancy. The impact of pregnancy on expressed autoimmunity increased with each...

  15. Epigenetic alterations underlying autoimmune diseases.

    Science.gov (United States)

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-01-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.

  16. Sex differences in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Voskuhl Rhonda

    2011-01-01

    Full Text Available Abstract Women are more susceptible to a variety of autoimmune diseases including systemic lupus erythematosus (SLE, multiple sclerosis (MS, primary biliary cirrhosis, rheumatoid arthritis and Hashimoto's thyroiditis. This increased susceptibility in females compared to males is also present in animal models of autoimmune diseases such as spontaneous SLE in (NZBxNZWF1 and NZM.2328 mice, experimental autoimmune encephalomyelitis (EAE in SJL mice, thyroiditis, Sjogren's syndrome in MRL/Mp-lpr/lpr mice and diabetes in non-obese diabetic mice. Indeed, being female confers a greater risk of developing these diseases than any single genetic or environmental risk factor discovered to date. Understanding how the state of being female so profoundly affects autoimmune disease susceptibility would accomplish two major goals. First, it would lead to an insight into the major pathways of disease pathogenesis and, secondly, it would likely lead to novel treatments which would disrupt such pathways.

  17. Autoimmune Hepatitis and PSC Connection.

    Science.gov (United States)

    Vergani, Diego; Mieli-Vergani, Giorgina

    2008-02-01

    This article describes the connection between autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). The two conditions have chronicity, liver inflammation, and a positive autoimmune serology in common; they differ in terms of gender distribution and bile duct damage. There is evidence suggesting that AIH and PSC are immune-mediated diseases. PSC and AIH could lie within the spectrum of the same disease process. Future studies should determine how frequently AIH evolves to PSC.

  18. [Sexuality and auto-immunity].

    Science.gov (United States)

    Abraham, Georges; Vlatkovic, Dejan

    2010-03-24

    The idea that it might be a link between auto-immune affections and sexual disturbances could appear a vain purpose at a first glance. Nevertheless, as we start from a new point of view, it is understandable that we focus on a possible common tendency to develop self-aggression and self-destruction. Similarities which could play a role in the development of an auto-immune disease and of a sexual dixturbance as well.

  19. Xenobiotic Exposure and Autoimmune Hepatitis

    Directory of Open Access Journals (Sweden)

    Kathleen M. Gilbert

    2010-01-01

    Full Text Available Although genetics contributes to the development of autoimmune diseases, it is clear that “environmental” factors are also required. These factors are thought to encompass exposure to certain drugs and environmental pollutants. This paper examines the mechanisms that normally maintain immune unresponsiveness in the liver and discusses how exposure to certain xenobiotics such as trichloroethylene may disrupt those mechanisms and promote autoimmune hepatitis.

  20. Loss of interleukin-21 leads to atrophic germinal centers in multicentric Castleman's disease.

    Science.gov (United States)

    Yajima, Hidetaka; Yamamoto, Motohisa; Shimizu, Yui; Sakurai, Nodoka; Suzuki, Chisako; Naishiro, Yasuyoshi; Imai, Kohzoh; Shinomura, Yasuhisa; Takahashi, Hiroki

    2016-01-01

    Both multicentric Castleman's disease (MCD) and immunoglobulin (Ig)G4-related disease (IgG4-RD) are systemic diseases, presenting with hypergammaglobulinemia and elevated serum levels of IgG4. However, with regard to histopathological findings, MCD shows atrophic germinal centers. On the other hand, expanded germinal centers are detected in IgG4-RD. We extracted germinal centers from specimens of each disorder by microdissection and analyzed the expression of mRNAs by real-time polymerase chain reaction to clarify the mechanisms underlying atrophied germinal centers in MCD. This analysis disclosed loss of interleukin (IL)-21 and B cell lymphoma (Bcl)-6 in the germinal centers of MCD. Loss of IL-21 is considered to be involved in the disappearance of Bcl-6 and leads to atrophied germinal centers in MCD.

  1. Restoration of an atrophic eye socket with custom made eye prosthesis, utilizing digital photography

    Directory of Open Access Journals (Sweden)

    Gaurav P Jayaswal

    2011-01-01

    Full Text Available Ocular defects may cause several ocular and orbital disorders, which require surgical intervention. These defects are psychologically disturbing for the patients, and therefore, they require immediate management and rehabilitation by a team of specialist. Ocular prosthesis may be either readymade (stock or custom made. Fabrication of a custom ocular prosthesis allows for a range of variations during construction. The iris can also be custom made by ocular painting or by digital photography. The optimum cosmetic and functional results of a custom-made prosthesis enhance the patient′s rehabilitation to a normal life style. This paper elaborates the technique for fabrication of a custom-made ocular prosthesis for an atrophic eye socket utilizing digital photography.

  2. The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage

    Science.gov (United States)

    Varanita, Tatiana; Soriano, Maria Eugenia; Romanello, Vanina; Zaglia, Tania; Quintana-Cabrera, Rubén; Semenzato, Martina; Menabò, Roberta; Costa, Veronica; Civiletto, Gabriele; Pesce, Paola; Viscomi, Carlo; Zeviani, Massimo; Di Lisa, Fabio; Mongillo, Marco; Sandri, Marco; Scorrano, Luca

    2015-01-01

    Summary Mitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence that it regulates the response of multiple tissues to apoptotic, necrotic, and atrophic stimuli. Genetic inhibition of the cristae remodeling pathway in vivo does not affect development, but protects mice from denervation-induced muscular atrophy, ischemic heart and brain damage, as well as hepatocellular apoptosis. Mechanistically, OPA1-dependent mitochondrial cristae stabilization increases mitochondrial respiratory efficiency and blunts mitochondrial dysfunction, cytochrome c release, and reactive oxygen species production. Our results indicate that the OPA1-dependent cristae remodeling pathway is a fundamental, targetable determinant of tissue damage in vivo. PMID:26039448

  3. Autoimmune Pancreatitis: An Update on Diagnosis and Management.

    Science.gov (United States)

    Madhani, Kamraan; Farrell, James J

    2016-03-01

    There is an evolving understanding that autoimmune pancreatitis (AIP) is an immunoglobulin (Ig) G4 systemic disease. It can manifest as primarily a pancreatic disorder or in association with other disorders of presumed autoimmune cause. Classic clinical characteristics include obstructive jaundice, abdominal pain, and acute pancreatitis. Thus, AIP can be difficult to distinguish from pancreatic malignancy. However, AIP may respond to therapy with corticosteroids, and has a strong association with other immune mediated diseases. Although primarily a pathologic diagnosis, attempts have been made to reliably diagnose AIP clinically. AIP can be classified as either type 1 or type 2.

  4. Local inhibition of angiogenesis results in an atrophic non-union in a rat osteotomy model

    Directory of Open Access Journals (Sweden)

    M Fassbender

    2011-07-01

    Full Text Available Long bone and in particular tibia fractures frequently fail to heal. A disturbed revascularisation is supposed to be a major cause for impaired bone healing or the development of non-unions. We aim to establish an animal model, which reliably mimics the clinical situation. Human microvascular endothelial cells (HMEC-1 and primary human osteoblast like cells (POBs were cultured with different angiogenesis-inhibitors (Fumagillin, SU5416, Artesunate and 3,5,4’-Trimethoxystilbene released out of poly(D,L-Lactide (PDLLA coated k-wires and cell activity was determined. Discs containing PDLLA or PDLLA + Fumagillin/Artesunate were placed at the chorionallantoic membrane of hen eggs and the effect on vessel formation and egg vitality was observed. Tibia osteotomy was performed in rats and stabilised with K-wires coated with PDLLA + Fumagillin or with PDLLA only (control group. The healing was compared at different time points to the PDLLA control. Fumagillin and Artesunate inhibited the activity of HMEC-1 with minor effect on POBs. Artesunate caused embryonic death, whereas Fumagillin had no effects on egg vitality, but reduced the blood vessels. In the animal study all rats showed an impaired healing with reduced biomechanical stability. The Fumagillin treated tibiae had a significantly decreased callus size at day 42 and 84, less blood vessels in the early callus, a reduced histological callus size at day 10, 28 and 84, as well as an altered callus composition. This study presents a less vascularised, atrophic, tibia non-union and can be used in further investigations to analyse the pathology of atrophic non-union and to test new interventions.

  5. Mesenchymal stem cell implantation in atrophic nonunion of the long bones

    Science.gov (United States)

    Phedy, P.; Kholinne, E.; Djaja, Y. P.; Kusnadi, Y.; Merlina, M.; Yulisa, N. D.

    2016-01-01

    Objectives To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone. Methods Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm3 (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm3 HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment. Results Post-operative pain evaluation showed no significant differences between the two groups. The treatment group demonstrated faster initial radiographic and functional improvements. Statistically significant differences in functional scores were present during the first (p = 0.002), second (p = 0.005) and third (p = 0.01) month. Both groups achieved similar outcomes by the end of one-year follow-up. No immunologic or neoplastic side effects were reported. Conclusions All cases of nonunion of a long bone presented in this study were successfully treated using autologous BM-MSCs. The combination of autologous BM-MSCs and HA granules is a safe method for treating nonunion. Patients treated with BM-MSCs had faster initial radiographic and functional improvements. By the end of 12 months, both groups had similar outcomes. Cite this article: H.D. Ismail, P. Phedy, E. Kholinne, Y. P. Djaja, Y. Kusnadi, M. Merlina, N. D. Yulisa. Mesenchymal stem cell implantation in atrophic nonunion of the long bones: A translational study. Bone Joint Res 2016;5:287–293. DOI: 10.1302/2046-3758.57.2000587. PMID:27412657

  6. Relation of atrophic gastritis with Helicobacter pylori-CagA+and interleukin-1 gene polymorphisms

    Institute of Scientific and Technical Information of China (English)

    Rafaela Sierra; Francis Mégraud; Clas Une; Vanessa Ramírez; Warner Alpízar-Alpízar; María I González; José A Ramírez; Antoine de Mascarel; Patricia Cuenca; Guillermo Pérez-Pérez

    2008-01-01

    AIM: To determine the association of Helicobacter pylori (H pylon) CagA+ infection and pro-inflammatory poly-morphisms of the genes interleukin (IL)-IRN and IL-1B with the risk of gastric atrophy and peptic ulcers in a dyspeptic population in Costa Rica, a country with high incidence and mortality of gastric cancer. METHODS: Seven biopsy specimens, a fasting blood sample and a questionnaire concerning nutritional and sociodemographic factors were obtained from 501 con-secutive patients who had undergone endoscopy for dyspeptic symptoms. A histopathological diagnosis was made. Pepsinogen concentrations were analyzed by enzyme linked immunosorbent assay (ELISA). Infection with H pylori CagA* was determined by serology and polymerase chain reaction (PCR). IL-1B and IL-1RN polymorphisms genotyping was performed by PCR-restriction fragment length polymorphism (PCR-RFLP) and PCR respectively. RESULTS: In this dyspeptic population, 86% wereHpy/ori positive and of these, 67.8% were positive forCagA. Atrophic antral gastritis (AAG) was associatedwith CagA+ status [odd ratio (OR) = 4.1; P < 0.000]and fruit consumption (OR = 0.3; P < 0.00). Atrophicbody gastritis (ABG) was associated with pepsinogenPGI/PGII < 3.4 (OR = 4.9; P < 0.04) and alcoholconsumption (OR = 7.3; P < 0.02). Duodenal ulcerwas associated with CagA+ (OR = 2.9; P < 0.04) andsmoking (OR = 2.4; P < 0.04). PGI < 60 μg/L as wellas PGI/PGII < 3.4 were associated with CagA+. CONCLUSION: In a dyspeptic population in Costa Rica,H pylori CagA+ is not associated with ABG, but it is arisk factor for AAG. The pro-inflammatory cytokine poly-morphisms IL-1B + 3945 and IL-1RN are not associatedwith the atrophic lesions of this dyspeptic population.

  7. A comparative study of vaginal estrogen cream and sustained-release estradiol vaginal tablet (Vagifem in the treatment of atrophic vaginitis in Isfahan, Iran in 2010-2012

    Directory of Open Access Journals (Sweden)

    Pardis Hosseinzadeh

    2015-01-01

    Full Text Available Background: Atrophic vaginitis is a disease, which affects up to 50% of postmenopausal women. This study compared the effectiveness and user-friendliness of Vagifem (an estradiol vaginal tablet and vaginal estrogen cream in the treatment of atrophic vaginitis. Materials and Methods: One hundred and sixty postmenopausal women with symptoms of atrophic vaginitis were randomly divided into two groups of treatment with Vagifem or with vaginal estrogen cream for 12 weeks. Patients used the medication daily for the first 2 weeks of the study, and twice weekly. Severity of vaginal atrophy and four main symptoms of atrophic vaginitis including dysuria, dyspareunia, vaginal itching, and dryness were evaluated and compared before and after treatment. In addition, patients were asked regarding user-friendliness and hygienic issues of medications. Results: Both vaginal estrogen cream and Vagifem significantly improved symptoms of atrophic vaginitis but in terms of effectiveness for the treatment symptoms of atrophic vaginitis, there was no significant difference between the two medications. Vagifem compared to estrogen cream resulted in significantly lower rate of hygienic problems (0% versus 23%, P < 0.001, and was reported by the patients as a significantly easier method of treatment (90% versus 55%, P < 0.0001. Conclusion: This investigation showed that Vagifem is an appropriate medication for the treatment of atrophic vaginitis, which is as effective as vaginal estrogen creams and is more user-friendly.

  8. Autoimmune NMDA receptor encephalitis.

    Science.gov (United States)

    Lazar-Molnar, Eszter; Tebo, Anne E

    2015-01-01

    Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a treatable autoimmune disease of the central nervous system (CNS) with prominent neurologic and psychiatric features at disease onset. The disease is associated with the production of autoantibodies to NMDAR, a protein involved in memory function and synaptic plasticity. Affected patients develop a multistage progressive illness with symptoms ranging from memory deficits, seizures and psychosis, to potentially lethal catatonia, and autonomic and breathing instability. The outcome can be much improved with accurate diagnosis and early treatment using adequate immunosuppressive therapy. However, since the neurological and psychiatric symptoms as well as the clinical examination results can be non-specific, the disease is probably under-recognized. Reliable and accurate clinical testing for the identification of NMDAR autoantibodies is crucial for diagnosis, timely treatment selection, and monitoring. Recently, a cell-based indirect immunofluorescent antibody test for the detection of IgG antibodies to NMDAR has become available for diagnostic use. This review highlights the progress and challenges of laboratory testing in the evaluation and management anti-NMDAR encephalitis, and perspectives for the future.

  9. Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Larsen, Janni Lisander; Jacobsen, Soren

    2013-01-01

    To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre...

  10. Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype

    DEFF Research Database (Denmark)

    Hawa, Mohammed I; Kolb, Hubert; Schloot, Nanette

    2013-01-01

    OBJECTIVESSpecific autoantibodies characterize type 1 diabetes in childhood but are also found in adult-onset diabetes, even when initially non-insulin requiring, e.g., with latent autoimmune diabetes (LADA). We aimed to characterize adult-onset autoimmune diabetes.RESEARCH DESIGN AND METHODSWe c...

  11. Comprehensive Investigation of Areae Gastricae Pattern in Gastric Corpus using Magnifying Narrow Band Imaging Endoscopy in Patients with Chronic Atrophic Fundic Gastritis

    Science.gov (United States)

    Kanzaki, Hiromitsu; Uedo, Noriya; Ishihara, Ryu; Nagai, Kengo; Matsui, Fumi; Ohta, Takashi; Hanafusa, Masao; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Iishi, Hiroyasu; Tomita, Yasuhiko; Tatsuta, Masaharu; Yamamoto, Kazuhide

    2012-01-01

    Background: Barium radiographic studies have suggested the importance of evaluating areae gastricae pattern for the diagnosis of gastritis. Significance of endoscopic appearance of areae gastricae in the diagnosis of chronic atrophic fundic gastritis (CAFG) was investigated by image-enhanced endoscopy. Materials and Methods: Endoscopic images of the corpus lesser curvature were studied in 50 patients with CAFG. Extent of CAFG was evaluated with autofluorescence imaging endoscopy. The areae gastricae pattern was evaluated with 0.2% indigo carmine chromoendoscopy. Micro-mucosal structure was examined with magnifying chromoendoscopy and narrow band imaging. Results: In patients with small extent of CAFG, polygonal areae gastricae separated by a narrow intervening part of areae gastricae was observed, whereas in patients with wide extent of CAFG, the size of the areae gastricae decreased and the width of the intervening part of areae gastricae increased (p < 0.001). Most areae gastricae showed a foveola-type micro-mucosal structure (82.7%), while intervening part of areae gastricae had a groove-type structure (98.0%, p < 0.001). Groove-type mucosa had a higher grade of atrophy (p < 0.001) and intestinal metaplasia (p < 0.001) compared with foveola type. Conclusions: As extent of CAFG widened, multifocal groove-type mucosa that had high-grade atrophy and intestinal metaplasia developed among areae gastricae and increased along the intervening part of areae gastricae. Our observations facilitate our understanding of the development and progression of CAFG. PMID:22515361

  12. MHC class II polymorphisms, autoreactive T-cells and autoimmunity

    Directory of Open Access Journals (Sweden)

    Sue eTsai

    2013-10-01

    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.

  13. Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Thyroid Autoimmunity

    Science.gov (United States)

    Watad, Abdulla; David, Paula; Brown, Stav; Shoenfeld, Yehuda

    2017-01-01

    The autoimmune/inflammatory syndrome induced by adjuvants (ASIA), presented by Shoenfeld and Agmon-Levin in 2011, is an entity that incorporates diverse autoimmune conditions induced by the exposure to various adjuvants. Adjuvants are agents that entail the capability to induce immune reactions. Adjuvants are found in many vaccines and used mainly to increase the response to vaccination in the general population. Silicone has also been reported to be able to induce diverse immune reactions. Clinical cases and series of heterogeneous autoimmune conditions including systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis have been reported to be induced by several adjuvants. However, only a small number of cases of autoimmune thyroid disorder have been included under the umbrella of ASIA syndrome. Indeed, clinical cases of Hashimoto’s thyroiditis and/or subacute thyroiditis were observed after the exposure to vaccines as well as silicone implantation. In our review, we aimed to summarize the current knowledge on ASIA syndrome presented as endocrinopathies, focusing on autoimmune thyroid disorders associated with the various adjuvants. PMID:28167927

  14. AUTOIMMUNE EPIDERMAL BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-11-01

    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

  15. Lack of an Association between Autoimmune Pancreatitis and Varicella Zoster Virus

    Directory of Open Access Journals (Sweden)

    Neal C Patel

    2011-11-01

    Full Text Available Dear Sir: Autoimmune pancreatitis is a form of chronic pancreatitis that was first described by Sarles et al. in 1961, and later coined in 1995 by Yoshida et al. [1, 2]. Subsequently, two types of autoimmune pancreatitis have been described. Autoimmune pancreatitis type 1 fits the classic description of the disease and is associated with a lymphoplasmacytic sclerosing pancreatitis and an elevated level of immunoglobulin G4 subclass of IgG. Autoimmune pancreatitis type 2 is characterized by a distinct neutrophilic obliterating lesion of the ductal epithelium [3]. Although the histopathological findings of autoimmune pancreatitis are well studied, the risk factors, pathogenesis, and treatments are still not well understood. There have been many hypotheses to the etiology of autoimmune pancreatitis, which are still being studied. One proposed theory is that of microbial mimicry leading to an autoimmune disorder. Several studies have been conducted to evaluate for a link with autoimmune pancreatitis and infectious causes, such as Helicobacter Pylori, without identifying a clear relationship [4]. Additionally, there has been a reported link between viral infections and acute pancreatitis, such as Coxackievirus [5].

  16. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M

    2012-02-03

    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.

  17. Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus.

    Science.gov (United States)

    Brooks, Wesley H; Renaudineau, Yves

    2015-01-01

    Autoimmune diseases occur more often in females, suggesting a key role for the X chromosome. X chromosome inactivation, a major epigenetic feature in female cells that provides dosage compensation of X-linked genes to avoid overexpression, presents special vulnerabilities that can contribute to the disease process. Disruption of X inactivation can result in loss of dosage compensation with expression from previously sequestered genes, imbalance of gene products, and altered endogenous material out of normal epigenetic context. In addition, the human X has significant differences compared to other species and these differences can contribute to the frequency and intensity of the autoimmune disease in humans as well as the types of autoantigens encountered. Here a link is demonstrated between autoimmune diseases, such as systemic lupus erythematosus, and the X chromosome by discussing cases in which typically non-autoimmune disorders complicated with X chromosome abnormalities also present lupus-like symptoms. The discussion is then extended to the reported spatial and temporal associations of the inactive X chromosome with the nucleolus. When frequent episodes of cellular stress occur, the inactive X chromosome may be disrupted and inadvertently become involved in the nucleolar stress response. Development of autoantigens, many of which are at least transiently components of the nucleolus, is then described. Polyamines, which aid in nucleoprotein complex assembly in the nucleolus, increase further during cell stress, and appear to have an important role in the autoimmune disease process. Autoantigenic endogenous material can potentially be stabilized by polyamines. This presents a new paradigm for autoimmune diseases: that many are antigen-driven and the autoantigens originate from altered endogenous material due to episodes of cellular stress that disrupt epigenetic control. This suggests that epigenetics and the X chromosome are important aspects of autoimmune

  18. Therapeutic apheresis in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Bambauer R

    2013-11-01

    Full Text Available Rolf Bambauer,1 Reinhard Latza,2 Carolin Bambauer,3 Daniel Burgard,4 Ralf Schiel5 1Institute for Blood Purification, Homburg, 2Laboratorium of Medicine, St Ingbert, 3Main Hospital Darmstadt, Darmstadt, 4Herz Zentrum, Cardiology, Völklingen, 5Inselklinik Heringsdorf GmbH, Seeheilbad Heringsdorf, Germany Abstract: Systemic autoimmune diseases based on an immune pathogenesis produce autoantibodies and circulating immune complexes, which cause inflammation in the tissues of various organs. In most cases, these diseases have a bad prognosis without treatment. Therapeutic apheresis in combination with immunosuppressive therapies has led to a steady increase in survival rates over the last 35 years. Here we provide an overview of the most important pathogenic aspects indicating that therapeutic apheresis can be a supportive therapy in some systemic autoimmune diseases, such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, and inflammatory eye disease. With the introduction of novel and effective biologic agents, therapeutic apheresis is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents, and in patients with renal involvement, acute generalized vasculitis, thrombocytopenia, leucopenia, pulmonary, cardiac, or cerebral involvement. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved considerably in recent years, due in part to very aggressive therapy schemes. Keywords: therapeutic apheresis, autoimmune diseases, systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, inflammatory eye disease

  19. CT and MRI Findings of Autoimmune Polymorph Bifocal Pancreatitis Mimicking Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Roman Rotzinger MD

    2015-03-01

    Full Text Available Autoimmune pancreatitis is a rare type of chronic pancreatitis. It is supposed to be a pancreatic manifestation of an immune-complex modulated systemic disorder. In contrast, pancreatic adenocarcinoma is the most frequent malignant neoplasm of the pancreas. Within the rare type of focal autoimmune pancreatitis, only few presentations with multifocal pancreatic lesions have been described. Herein we report a case of a 58-year-old patient with autoimmune pancreatitis presenting with bifocal manifestations of the pancreatic head and tail, mimicking pancreatic adenocarcinoma clinically, on computed tomography and magnetic resonance imaging. Typical imaging findings of autoimmune pancreatitis are compared with typical findings in pancreatic carcinoma. The diagnostic dilemma of differentiating between both entities is discussed. A review of the present literature regarding multifocal presence of autoimmune pancreatitis is performed.

  20. The immunogenetics of autoimmune diabetes and autoimmune thyroid disease.

    Science.gov (United States)

    Tomer, Y; Barbesino, G; Greenberg, D; Davies, T F

    1997-03-01

    Although medical genetics is a well-developed area of interest, relatively little is known about the diseases caused by the combination of many genes. These multiinfluenced diseases include the autoimmune endocrine diseases. Recent advances in the techniques for whole-genome screening have shown a variety of loci that are linked to the development of insulin-dependent diabetes mellitus, and similar data are likely to be soon generated in autoimmune thyroid disease. Here, the authors survey the current state of genetic knowledge in these two areas and describe the investigative and analytical techniques that are now available. (Trends Endocrinol Metab 1997;8:63-70). (c) 1997, Elsevier Science Inc.

  1. PD-1, gender, and autoimmunity

    Science.gov (United States)

    Dinesh, Ravi K.; Hahn, Bevra H.; Singh, Ram Pyare

    2010-01-01

    Programmed death 1 (PD-1) and its ligands (PD-L1 and PD-L2) are responsible for inhibitory T cell signaling that helps mediate the mechanisms of tolerance and immune homeostasis. The PD-1:PD-L signaling pathway has been shown to play an important role in a variety of diseases, including autoimmune conditions, chronic infection, and cancer. Recently, investigators have explored the role of sex hormones in modulating the pathway in autoimmune conditions. Exploring the effects of sex hormones on the PD-1:PD-L pathway could shed light on the gender biased nature of many autoimmune conditions as well as aide in the development of therapeutics targeting the immune system. PMID:20433954

  2. Distinct monocyte Gene-Expression profiles in autoimmune diabetes

    NARCIS (Netherlands)

    R.C. Padmos (Roos); N.C. Schloot (Nanette); H. Beyan (Huriya); C. Ruwhof (Cindy); F.J.T. Staal (Frank); D. de Ridder (Dick); H-J. Aanstoot (Henk-Jan); W.K. Lam-Tse; H.J. de Wit (Harm); C. Herder (Christian); R.C. Drexhage (Roos); B. Menart (Barbara); R.D. Leslie

    2008-01-01

    textabstractOBJECTIVE-There is evidence that monocytes of patients with type 1 diabetes show proinflammatory activation and disturbed migration/adhesion, but the evidence is inconsistent. Our hypothesis is that monocytes are distinctly activated/disturbed in different subforms of autoimmune diabetes

  3. Human T-Cell Lymphotropic Virus Type I (HTLV-1: implications for autoimmune diseases Vírus linfotrópico de células T humano tipo 1 (HTLV-1: implicações em doenças autoimunes

    Directory of Open Access Journals (Sweden)

    Dênis Augusto Santana Reis

    2012-06-01

    Full Text Available Autoimmunity is characterized by tissue destruction that implicates functional damages caused by self-reactive cells that escape self-tolerance mechanisms. Autoimmune diseases can be initiated by viral infections and the study of the association between these viruses and autoimmunity has advanced the understanding of the molecular mechanisms involved in autoimmune diseases. The Human T-Cell Lymphotropic Virus Type I (HTLV-1 is a deltavirus that infects preferentially lymphocytes. Retrovirus particles like has been identified in patients with autoimmune diseases. Therefore this review had by objective approach the main aspects involving HTLV-1 with systemic lupus erythematosus and rheumatoid arthritis. Studies show that retroviruses can integrate their genetic material in host DNA, changing the expression gene profile related with apoptosis and immunologic system molecules. It’s known that HTLV-1 can cause different clinical manifestations in their careers and the mechanisms that triggers the HTLV-1 associated autoimmune diseases are not well known. Besides the perpetuation and marked production of pro-inflammatory cytokines, studies have demonstrated that both Th17 cells and T regulatory cells (Tregs are involved in autoimmune diseases pathogenesis. Therefore the HTLV-1 viral particles recognized could be used as a risk marker in the development of autoimmune diseases.A autoimunidade é caracterizada pela destruição tecidual, que acarreta danos funcionais, causados por células autoreativas que escapam dos mecanismos de autotolerância. Doenças autoimunes podem ser iniciadas por infecções virais e o estudo da associação entre essas viroses e a autoimunidade tem possibilitado melhor conhecimento dos mecanismos moleculares envolvidos nas doenças autoimunes. O vírus linfotrópico de células T humano tipo 1 (HTLV-1 é um delta vírus que infecta preferencialmente linfócitos. Partículas semelhantes aos retrovírus foram identificadas em

  4. Environmental triggers and epigenetic deregulation in autoimmune disease.

    Science.gov (United States)

    Javierre, Biola M; Hernando, Henar; Ballestar, Esteban

    2011-12-01

    The study of epigenetic mechanisms in the pathogenesis of autoimmune diseases is receiving unprecedented attention from clinicians and researchers in the field. Autoimmune disorders comprise a wide range of genetically complex diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. Together they affect a significant proportion of the population and have a great economic impact on public health systems. Epigenetic mechanisms control gene expression and are influenced by external stimuli, linking environment and gene function. A variety of environmental agents, such as viral infection, hormones, certain drugs, and pollutants, have been found to influence the development of autoimmune diseases. On the other hand, there is considerable evidence of epigenetic changes, particularly DNA methylation alterations, in diseases like systemic lupus erythematosus, rheumatoid arthritis, or multiple sclerosis. However, the gap in our understanding between the specific effects of external agents and the influence on epigenetic profiles has not yet been filled. Here we review a number of studies describing epigenetic alterations in autoimmune diseases and a range of environmental factors that influence the development of autoimmune diseases. We also discuss potential mechanisms linking environment and epigenetics, consider the prospects for future epigenetic studies addressing the relationship between environment and epigenetics, and comment on the use of drugs with an epigenetic-reversing effect in the clinical management of these diseases.

  5. [The application of helium-neon laser radiation for the combined treatment of the patients with atrophic rhinitis].

    Science.gov (United States)

    Sharipov, R A; Sharipova, E R

    2012-01-01

    The objective of the present study was to improve the efficacy of the treatment of the patients presenting with atrophic rhinitis (ozena) of the upper respiratory tract by the application of helium-neon laser radiation. A total of 120 patients aged from 15 to 53 years were treated based at the Department of Otorhinolaryngology, G.G. Kuvatov Republican Clinical Hospital, Ufa. All these patients underwent routine clinical, roentgenological, microbiological, and rheographic examination. The method for the treatment of atrophic rhinitis is described; it includes the application of helium-neon laser radiation in combination with the administration of the purified preparation of liquid polyvalent Klebsiella bacteriophage. The positive results of the treatment by the proposed method were documented in 90% of the patients.

  6. Clinical and Histological Results of Vertical Ridge Augmentation of Atrophic Posterior Mandible with Inlay Technique of Cancellous Equine Bone Blocks

    Directory of Open Access Journals (Sweden)

    Pistilli R

    2013-12-01

    Full Text Available Aim: We want to evaluate a new bone block material in the inlay technique, for the vertical bone augmentation of a posterior atrophic mandible, in order to perfom aesthetic and prosthetic rehabilitation and enable implant insertion. Materials & Methods: Inlay technique and the subsequent successful implant rehabilitation in the atrophic right posterior mandible in a 42-year-old woman, was completed using a cancellous equine bone block as grafting material. Results: Three months after surgical procedure both clinical and histological aspects show complete integration of the biomaterial with the surrounding bone and three dental implants were placed. Computed tomography and conventional radiography showed a 5mm mean vertical bone gain. Conclusion: Cancellous equine bone grafts may be an effective alternative to autogenous bone and/or inorganic bovine bone for reconstruction of the posterior mandible using inlay technique.

  7. Interleukin-22: a likely target for treatment of autoimmune diseases

    Science.gov (United States)

    Yang, Xuyan; Zheng, Song Guo

    2014-01-01

    Interleukin -22 (IL-22) is a member of IL-10 family cytokines that is produced by many different types of lymphocytes including both those of the innate and adaptive immune system. This includes activated T cells, most notably Th17 and Th22 cells, and NK cells, γδ T cells, LTi cells and LTi-like cells. IL-22 mediates its effects via the IL-22-IL-22R complex and subsequent Janus Kinase-signal transduces and activators transcription (JAK-STAT) signaling pathway. Recently accumulated evidence has indicated that IL-22 also plays an important role in the pathogenesis of many autoimmune diseases. In this review, we discuss the recent findings and advancement of the role for IL-22 in several autoimmune diseases, such as psoriasis, rheumatoid arthritis (RA), hepatitis, graft versus host disease (GHVD) and allergic diseases, implicating that target IL-22 may have a therapeutic potential in those autoimmune diseases. PMID:24418299

  8. Alopecia areata and narcolepsy: a tale of obscure autoimmunity.

    Science.gov (United States)

    Nigam, Gaurav; Pathak, Charu; Riaz, Muhammad

    2016-04-08

    Alopecia areata is an autoimmune dermatological disorder characterised by loss of hair in one or more discrete patches over the scalp. It has been linked to multiple disorders having an autoimmune origin. Like many autoimmune disorders it tends to be more common in females. To date, only five cases have been reported where alopecia has been associated with narcolepsy. Male gender is less commonly affected by alopecia areata. No case of alopecia areata in males has been associated with narcolepsy to the best of our knowledge. The current case represents the first ever-reported case of alopecia areata in a male patient with narcolepsy type 1. This coexistence is most likely the manifestation of a common underlying pathoimmunological mechanism that has not been completely understood, rather than a random association.

  9. Autoimmune diseases in the TH17 era

    Directory of Open Access Journals (Sweden)

    D. Mesquita Jr.

    2009-06-01

    Full Text Available A new subtype of CD4+ T lymphocytes characterized by the production of interleukin 17, i.e., TH17 cells, has been recently described. This novel T cell subset is distinct from type 1 and type 2 T helper cells. The major feature of this subpopulation is to generate significant amounts of pro-inflammatory cytokines, therefore appearing to be critically involved in protection against infection caused by extracellular microorganisms, and in the pathogenesis of autoimmune diseases and allergy. The dynamic balance among subsets of T cells is important for the modulation of several steps of the immune response. Disturbances in this balance may cause a shift from normal immunologic physiology to the development of immune-mediated disorders. In autoimmune diseases, the fine balance between the proportion and degree of activation of the various T lymphocyte subsets can contribute to persistent undesirable inflammatory responses and tissue replacement by fibrosis. This review highlights the importance of TH17 cells in this process by providing an update on the biology of these cells and focusing on their biology and differentiation processes in the context of immune-mediated chronic inflammatory diseases.

  10. Predictability of short implants (< 10 mm) as a treatment option for the rehabilitation of atrophic maxillae. A systematic review

    OpenAIRE

    Sierra Sánchez, José Luis; García-Sala Bonmatí, Fernando; Martínez González, Amparo; Garcia Dalmau, Carlos; Mañes Ferrer, José Félix; Brotóns Oliver, Alejandro

    2016-01-01

    Background Short implants (< 10 mm) are one of the treatment options available in cases of limited vertical bone. A purpose of this paper is to evaluate the predictability of short implants as an alternative to technically molthough such implants are now widely used, there is controversy regarding their clinical reliability. There complex treatments in patients with atrophic maxillae, based on a systematic review of the literature and the analysis of the implant survival rates, changes in per...

  11. Split Face Comparative Study of Microneedling with PRP Versus Microneedling with Vitamin C in Treating Atrophic Post Acne Scars

    OpenAIRE

    Simran Chawla

    2014-01-01

    Introduction: Acne scars are largely preventable complications of acne. 95% of the scars occur over the face thus impacting the quality of life. Correction of scars is the priority for acne patients. Materials and Methods: Thirty patients with post acne atrophic facial scars attending the OPD during the period from April to October 2013 were offered four sittings of microneedling with PRP on one side and microneedling with vitamin C on other side of the face at an interval of 1 month. Results...

  12. Caveolin-1, E-cadherin and β-catenin in Gastric Carcinoma, Precancerous Tissues and Chronic Non-atrophic Gastritis

    Institute of Scientific and Technical Information of China (English)

    Guo-yang Sun; Jun-xia Wu; Jian-sheng Wu; Yu-ting Pan; Rong Jin

    2012-01-01

    Objective:To investigate the expressions of caveolin-1,E-cadherin and β-catenin in gastric carcinoma,precancerous gastric and chronic non-atrophic gastritis tissues,and evaluate the correlation of these expressions with the development of gastric cancer.Methods:The expressions of caveolin-1,E-cadherin and β-catenin were detected by biotin-streptavidinperoxidase (SP) immunohistochemistry on 58 gastric cancer tissues,40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues.The correlation between the expressions of caveolin-1,E-cadherin and β-catenin,and the clinicopathologic parameters of gastric cancer was analyzed retrospectively.Results:The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues (P<0.01).An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues (P<0.01).Moreover,low expressions of caveolin-1,E-cadherin and β-catenin correlated with tumor size,depth of invasion,lymph node metastasis and TNM stage (P<0.05).The positive rates of caveolin-1 and E-cadherin expressions decreased (P<0.01),while an abnormal rate of β-catenin expression increased inversely,with the degree of atypical hyperplasia (P<0.01).Caveolin-1 expression correlated positively with E-cadherin (r=0.41,P<0.05).Caveolin-1 (r=-0.36,P<0.05) and E-cadherin (r=-0.45,P<0.05) expressions negatively correlated with abnormal β-catenin expression.Conclusion:These results suggested that dysregulated expressions of caveolin-1,E-cadherin and β-catenin correlated with the development of gastric cancer and its biological behavior.

  13. Artificial neural networks in the recognition of the presence of thyroid disease in patients with atrophic body gastritis

    Institute of Scientific and Technical Information of China (English)

    Edith Lahner; Marco Intraligi; Massimo Buscema; Marco Centanni; Lucy Vannella; Enzo Grossi; Bruno Annibale

    2008-01-01

    AIM: To investigate the role of artificial neural networks in predicting the presence of thyroid disease in atrophic body gastritis patients.METHODS: A dataset of 29 input variables of 253 atrophic body gastritis patients was applied to artificial neural networks (ANNs) using a data optimisation procedure (standard ANNs, T&T-IS protocol, TWIST protocol). The target variable was the presence of thyroid disease.RESULTS: Standard ANNs obtained a mean accuracy of 64.4% with a sensitivity of 69% and a specificity of 59.8% in recognizing atrophic body gastritis patients with thyroid disease. The optimization procedures (T&T-IS and TWIST protocol) improved the performance of the recognition task yielding a mean accuracy, sensitivity and specificity of 74.7% and 75.8%, 78.8% and 81.8%, and 70.5% and 69.9%, respectively. The increase of sensitivity of the TWIST protocol was statistically significant compared to T&T-IS.CONCLUSION: This study suggests that artificial neural networks may be taken into consideration as a potential clinical decision-support tool for identifying ABG patients at risk for harbouring an unknown thyroid disease and thus requiring diagnostic work-up of their thyroid status.

  14. The interaction between vitamin K nutriture and warfarin administration in patients with bacterial overgrowth due to atrophic gastritis.

    Science.gov (United States)

    Camilo, M E; Paiva, S A; O'Brien, M E; Booth, S L; Davidson, K W; Sokoll, L J; Sadowski, J A; Russell, R M

    1998-01-01

    Atrophic gastritis patients have intestinal bacterial overgrowth which could produce menaquinones. The aim of this study was to evaluate the interaction between a diet low in phylloquinone and minidoses of warfarin in subjects with and without bacterial overgrowth. Subjects with atrophic gastritis (indicated by serum pepsinogen ratio) and healthy volunteers were studied while fed a restrictive phylloquinone diet and while receiving a minidose of warfarin. Coagulation times, serum osteocalcin, serum undercarboxylated osteocalcin, plasma phylloquinone, plasma K-epoxide, plasma undercarboxylated prothrombin (PIVKA)-II and urinary gamma-carboxyglutamic acid (Gla) were measured. At baseline, there were no differences between groups for any variable measured. Comparisons between baseline and post intervention in both groups, showed significant increases in circulating levels of K-epoxide, PIVKA II and undercarboxylated osteocalcin. However, no differences were observed when comparisons were made between groups. Our data do not support the hypothesis that bacterial synthesis of menaquinones in patients with bacterial overgrowth due to atrophic gastritis confers considerable resistance to the effect of warfarin.

  15. Autoimmune Skin Diseases in the Dog

    OpenAIRE

    Parker, W. M.

    1981-01-01

    Diagnoses of autoimmune skin diseases require very careful observation of the skin lesions, and selection of an intact vesicle for histopathological examination. If available, immunofluorescent studies can be very useful in confirming the diagnosis of autoimmune skin disease. Seven autoimmune skin diseases are briefly reviewed. Therapy must be aggressive and owner warned of the guarded prognosis.

  16. Impaired translocation of GLUT4 results in insulin resistance of atrophic soleus muscle.

    Science.gov (United States)

    Xu, Peng-Tao; Song, Zhen; Zhang, Wen-Cheng; Jiao, Bo; Yu, Zhi-Bin

    2015-01-01

    Whether or not the atrophic skeletal muscle induces insulin resistance and its mechanisms are not resolved now. The antigravity soleus muscle showed a progressive atrophy in 1-week, 2-week, and 4-week tail-suspended rats. Hyperinsulinemic-euglycemic clamp showed that the steady-state glucose infusion rate was lower in 4-week tail-suspended rats than that in the control rats. The glucose uptake rates under insulin- or contraction-stimulation were significantly decreased in 4-week unloaded soleus muscle. The key protein expressions of IRS-1, PI3K, and Akt on the insulin-dependent pathway and of AMPK, ERK, and p38 on the insulin-independent pathway were unchanged in unloaded soleus muscle. The unchanged phosphorylation of Akt and p38 suggested that the activity of two signal pathways was not altered in unloaded soleus muscle. The AS160 and GLUT4 expression on the common downstream pathway also was not changed in unloaded soleus muscle. But the GLUT4 translocation to sarcolemma was inhibited during insulin stimulation in unloaded soleus muscle. The above results suggest that hindlimb unloading in tail-suspended rat induces atrophy in antigravity soleus muscle. The impaired GLUT4 translocation to sarcolemma under insulin stimulation may mediate insulin resistance in unloaded soleus muscle and further affect the insulin sensitivity of whole body in tail-suspended rats.

  17. Impaired Translocation of GLUT4 Results in Insulin Resistance of Atrophic Soleus Muscle

    Directory of Open Access Journals (Sweden)

    Peng-Tao Xu

    2015-01-01

    Full Text Available Whether or not the atrophic skeletal muscle induces insulin resistance and its mechanisms are not resolved now. The antigravity soleus muscle showed a progressive atrophy in 1-week, 2-week, and 4-week tail-suspended rats. Hyperinsulinemic-euglycemic clamp showed that the steady-state glucose infusion rate was lower in 4-week tail-suspended rats than that in the control rats. The glucose uptake rates under insulin- or contraction-stimulation were significantly decreased in 4-week unloaded soleus muscle. The key protein expressions of IRS-1, PI3K, and Akt on the insulin-dependent pathway and of AMPK, ERK, and p38 on the insulin-independent pathway were unchanged in unloaded soleus muscle. The unchanged phosphorylation of Akt and p38 suggested that the activity of two signal pathways was not altered in unloaded soleus muscle. The AS160 and GLUT4 expression on the common downstream pathway also was not changed in unloaded soleus muscle. But the GLUT4 translocation to sarcolemma was inhibited during insulin stimulation in unloaded soleus muscle. The above results suggest that hindlimb unloading in tail-suspended rat induces atrophy in antigravity soleus muscle. The impaired GLUT4 translocation to sarcolemma under insulin stimulation may mediate insulin resistance in unloaded soleus muscle and further affect the insulin sensitivity of whole body in tail-suspended rats.

  18. Sclerosus and atrophic genital Lichen or vulvar craurosis. About a case

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    Graciela Caridad Cabrera Acea

    2016-12-01

    Full Text Available Sclerosus and atrophic genital Lichen or vulvar craurosis is an affection characterized by a progressive chronic atrophy of the vulvar skin and mucosa, associated to involutive changes in external genitalia. The presentation of this case was motivated by the unusual appearance of it in our context. A 49 year old white patient with history of hypertension, came to the Dermatology consultation referred by her Family Doctor. She reported that she had had an intense pruritus since approximately eight months in the vulvar region and changes in texture which she stated as ¨hardening sensation¨ which had had intensified, so as irregularities in her menstrual period, all of which was not relieved with the usual treatment as it was interpreted as vaginal parasites. She explained that she suffered from an intense pain during intercourse, more frequently in the last months so as sleeping problems and nervousness. A biopsy was performed and it showed lichen sclerosus. It was treated with local high potency steroids, conjugated estrogens and psychological support. The patient had an evident symptom improvement. She has a periodic evaluation to avoid relapse and /or complications.

  19. Broccoli consumption and chronic atrophic gastritis among Japanese males: an epidemiological investigation.

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    Sato K

    2004-06-01

    Full Text Available Previous in vitro and animal experiments have shown that sulforaphane, which is abundant in broccoli, inhibits Helicobacter pylori (H. pylori infection and blocks gastric tumor formation. This suggests that broccoli consumption prevents chronic atrophic gastritis (CAG introduced by H. pylori infection and, therefore, gastric cancer. For an epidemiological investigation of the relationship between the broccoli consumption and CAG, a cross-sectional study of 438 male employees, aged 39 to 60 years, of a Japanese steel company was conducted. CAG was serologically determined with serum cut-off values set at pepsinogen I < or = 70 ng/ml and a ratio of serum pepsinogen I/pepsinogen II < or = 3.0. Broccoli consumption (weekly frequency and diet were monitored by using a 31-item food frequency questionnaire. The prevalence of CAG among men who ate broccoli once or more weekly was twice as high as that among men who consumed a negligible amount (P < 0.05. Multiple logistic regression analysis indicated that broccoli consumption once or more weekly significantly increased the risk for CAG (odds ratio, 3.06; 95% confidence interval, 1.12-8.38; P < 0.05, after controlling for age, education, cigarette smoking, and alcohol consumption. The present study failed to show an expected association between frequent broccoli consumption and a low prevalence of CAG.

  20. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis.

    Science.gov (United States)

    Shen, Jian; Song, Ning; Williams, Christopher J; Brown, Celeste J; Yan, Zheng; Xu, Chen; Forney, Larry J

    2016-01-01

    Atrophic vaginitis (AV) is common in postmenopausal women, but its causes are not well understood. The symptoms, which include vaginal itching, burning, dryness, irritation, and dyspareunia, can usually be alleviated by low doses of estrogen given orally or locally. Regrettably, the composition of vaginal bacterial communities in women with AV have not been fully characterized and little is known as to how these communities change over time in response to hormonal therapy. In the present intervention study we determined the response of vaginal bacterial communities in postmenopausal women with AV to low-dose estrogen therapy. The changes in community composition in response to hormonal therapy were rapid and typified by significant increases in the relative abundance of Lactobacillus spp. that were mirrored by a decreased relative abundance of Gardnerella. These changes were paralleled by a significant four-fold increase in serum estradiol levels and decreased vaginal pH, as well as nearly a two-fold increase in the Vaginal Maturation Index (VMI). The results suggest that after menopause a vaginal microbiota dominated by species of Lactobacillus may have a beneficial role in the maintenance of health and these findings that could lead to new strategies to protect postmenopausal women from AV.

  1. On the Feasibility of Utilizing Allogeneic Bone Blocks for Atrophic Maxillary Augmentation

    Directory of Open Access Journals (Sweden)

    Alberto Monje

    2014-01-01

    Full Text Available Purpose. This systematic review was aimed at assessing the feasibility by means of survival rate, histologic analysis, and causes of failure of allogeneic block grafts for augmenting the atrophic maxilla. Material and Methods. A literature search was conducted by one reviewer in several databases. Articles were included in this systematic review if they were human clinical trials in which outcomes of allogeneic bone block grafts were studied by means of survival rate. In addition other factors were extracted in order to assess their influence upon graft failure. Results. Fifteen articles fulfilled the inclusion criteria and subsequently were analyzed in this systematic review. A total of 361 block grafts could be followed 4 to 9 months after the surgery, of which 9 (2.4% failed within 1 month to 2 months after the surgery. Additionally, a weighed mean 4.79 mm (95% CI: 4.51–5.08 horizontal bone gain was computed from 119 grafted sites in 5 studies. Regarding implant cumulative survival rate, the weighed mean was 96.9% (95% CI: 92.8–98.7%, computed from 228 implants over a mean follow-up period of 23.9 months. Histologic analysis showed that allogeneic block grafts behave differently in the early stages of healing when compared to autogenous block grafts. Conclusion. Atrophied maxillary reconstruction with allogeneic bone block grafts represents a reliable option as shown by low block graft failure rate, minimal resorption, and high implant survival rate.

  2. NMR-based metabolomics Reveals Alterations of Electro-acupuncture Stimulations on Chronic Atrophic Gastritis Rats

    Science.gov (United States)

    Xu, Jingjing; Zheng, Xujuan; Cheng, Kian-Kai; Chang, Xiaorong; Shen, Guiping; Liu, Mi; Wang, Yadong; Shen, Jiacheng; Zhang, Yuan; He, Qida; Dong, Jiyang; Yang, Zongbao

    2017-01-01

    Chronic atrophic gastritis (CAG) is a common gastrointestinal disease which has been considered as precancerous lesions of gastric carcinoma. Previously, electro-acupuncture stimulation has been shown to be effective in ameliorating symptoms of CAG. However the underlying mechanism of this beneficial treatment is yet to be established. In the present study, an integrated histopathological examination along with molecular biological assay, as well as 1H NMR analysis of multiple biological samples (urine, serum, stomach, cortex and medulla) were employed to systematically assess the pathology of CAG and therapeutic effect of electro-acupuncture stimulation at Sibai (ST 2), Liangmen (ST 21), and Zusanli (ST 36) acupoints located in the stomach meridian using a rat model of CAG. The current results showed that CAG caused comprehensive metabolic alterations including the TCA cycle, glycolysis, membrane metabolism and catabolism, gut microbiota-related metabolism. On the other hand, electro-acupuncture treatment was found able to normalize a number of CAG-induced metabolomics changes by alleviating membrane catabolism, restoring function of neurotransmitter in brain and partially reverse the CAG-induced perturbation in gut microbiota metabolism. These findings provided new insights into the biochemistry of CAG and mechanism of the therapeutic effect of electro-acupuncture stimulations. PMID:28358020

  3. Time Course of Atrophic Remodeling: Effects of Exercise on Cardiac Morpology and Function

    Science.gov (United States)

    Scott, J. M.; Martin, D.; Caine, T.; Matz, T.; Ploutz-Snyder, L. L.

    2014-01-01

    Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. Exercise training is one intervention that has been shown to confer favorable improvements in LV mass and function during unloading. However, the format and intensity of exercise required to induce optimal cardiac improvements has not been investigated. PURPOSE: This randomized, controlled trial was designed to 1) comprehensively characterize the time course of unloading-induced morpho-functional remodeling, and 2) examine the effects of high intensity exercise training on cardiac structural and functional parameters during unloading. METHODS: Twenty six subjects completed 70 days of head down tilt bed rest (HDBR): 17 were randomized to exercise training (ExBR) and 9 remained sedentary. Exercise consisted of integrated high intensity, continuous, and resistance exercise. We assessed cardiac morphology (left ventricular mass; LVM) and function (speckle-tracking assessment of longitudinal, radial, and circumferential strain and twist) before (BR-2), during (BR7,21,31,70), and following (BR+0, +3) HDBR. Cardiorespiratory fitness (VO2max) was evaluated before (BR- 3), during (BR4,25,46,68) and following (BR+0) HDBR. RESULTS: Sedentary HDBR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain, and an increase in twist. ExBR mitigated decreases in LVM and function. Change in twist was significantly related to change in VO2max (R=0.68, premodeling.

  4. The critical role of epigenetics in systemic lupus erythematosus and autoimmunity.

    Science.gov (United States)

    Long, Hai; Yin, Heng; Wang, Ling; Gershwin, M Eric; Lu, Qianjin

    2016-11-01

    One of the major disappointments in human autoimmunity has been the relative failure on genome-wide association studies to provide "smoking genetic guns" that would explain the critical role of genetic susceptibility to loss of tolerance. It is well known that autoimmunity refers to the abnormal state that the dysregulated immune system attacks the healthy cells and tissues due to the loss of immunological tolerance to self-antigens. Its clinical outcomes are generally characterized by the presence of autoreactive immune cells and (or) the development of autoantibodies, leading to various types of autoimmune disorders. The etiology and pathogenesis of autoimmune diseases are highly complex. Both genetic predisposition and environmental factors such as nutrition, infection, and chemicals are implicated in the pathogenic process of autoimmunity, however, how much and by what mechanisms each of these factors contribute to the development of autoimmunity remain unclear. Epigenetics, which refers to potentially heritable changes in gene expression and function that do not involve alterations of the DNA sequence, has provided us with a brand new key to answer these questions. In the recent decades, increasing evidence have demonstrated the roles of epigenetic dysregulation, including DNA methylation, histone modification, and noncoding RNA, in the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE), which have shed light on a new era for autoimmunity research. Notably, DNA hypomethylation and reactivation of the inactive X chromosome are two epigenetic hallmarks of SLE. We will herein discuss briefly how genetic studies fail to completely elucidate the pathogenesis of autoimmune diseases and present a comprehensive review on landmark epigenetic findings in autoimmune diseases, taking SLE as an extensively studied example. The epigenetics of other autoimmune diseases such as rheumatic arthritis, systemic sclerosis and primary biliary

  5. The thyroid, iodine and autoimmunity

    NARCIS (Netherlands)

    P. Mooij (Petra)

    1993-01-01

    textabstractAn excessive dietary iodine intake has also been described to lead to thyroid autoimmune reactivity: a. in individuals with a preexisting thyroid abnormality, such as an iodine deficient goitre, an excessive dietary iodine intake results in a proportion of the individuals in the developm

  6. Therapeutic apheresis in autoimmune diseases

    Science.gov (United States)

    Bambauer, Rolf; Latza, Reinhard; Bambauer, Carolin; Burgard, Daniel; Schiel, Ralf

    2013-01-01

    Systemic autoimmune diseases based on an immune pathogenesis produce autoantibodies and circulating immune complexes, which cause inflammation in the tissues of various organs. In most cases, these diseases have a bad prognosis without treatment. Therapeutic apheresis in combination with immunosuppressive therapies has led to a steady increase in survival rates over the last 35 years. Here we provide an overview of the most important pathogenic aspects indicating that therapeutic apheresis can be a supportive therapy in some systemic autoimmune diseases, such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, and inflammatory eye disease. With the introduction of novel and effective biologic agents, therapeutic apheresis is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents, and in patients with renal involvement, acute generalized vasculitis, thrombocytopenia, leucopenia, pulmonary, cardiac, or cerebral involvement. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved considerably in recent years, due in part to very aggressive therapy schemes.

  7. Clinical phenotypes of autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy seen in the Northern Ireland paediatric population over the last 30 years.

    OpenAIRE

    Millar, Sarinda; Carson, Dennis

    2012-01-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyendocrinopathy syndrome type 1, is a rare autosomal recessive disorder with a variable and evolving phenotypic course. It is caused by mutations in the autoimmune regulator (AIRE) gene. APECED syndrome is diagnosed clinically by the presence of 2 from 3 major criteria; chronic mucocutaneous candidasis, primary hypoparathyroidism and primary adrenocortical insufficiency. Many of the patients d...

  8. Concurrent reactive arthritis, Graves' disease, and warm autoimmune hemolytic anemia: a case report.

    Science.gov (United States)

    Chiang, Elizabeth; Packer, Clifford D

    2009-08-13

    Warm antibody autoimmune hemolytic anemia is due to the presence of warm agglutinins that react with protein antigens on the surface of red blood cells causing premature destruction of circulating red blood cells. We report the first case of concurrent reactive arthritis, Graves' disease, and autoimmune hemolytic anemia. A 40-year-old man with reactive arthritis, Graves' disease, type 2 diabetes mellitus, mitral valve prolapse, and Gilbert's disease presented with a one month history of jaundice, fatigue, and black stools. After diagnosis of warm autoimmune hemolytic anemia, the patient was started on prednisone 1 mg/kg with rapid improvement in his anemia and jaundice. Our subject's mother and possibly his maternal grandmother also had autoimmune hemolytic anemia, which raises the possibility of hereditary autoimmune hemolytic anemia, a rarely reported condition.

  9. De novo autoimmune hepatitis after liver transplantation.

    Science.gov (United States)

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

    2007-10-01

    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

  10. Autoimmune pancreatitis mimicking Klatskin tumour on radiology.

    Science.gov (United States)

    Hadi, Yousaf Bashir; Sohail, Abdul Malik Amir Humza; Haider, Zishan

    2015-04-09

    Autoimmune pancreatitis (AIP) is categorised into two distinct types, AIP type 1 and 2. Although there can be multisystem involvement, rarely, the cholangitis associated with AIP can present radiologically in a manner similar to that of Klatskin tumour. We present the case of a 65-year-old man who was almost misdiagnosed with a Klatskin tumour because of the similarity in radiological features of the two aforementioned clinical entities. The patient presented with a history of jaundice, pruritus and abdominal pain, and work up showed deranged liver function tests, elevated cancer antigen 19-9 levels and positive antinuclear antibodies. CT scan of the abdomen showed findings suggestive of Klatskin tumour but due to diffuse enlargement of the pancreas and surrounding low-attenuation halo found on a closer review, a diagnosis of AIP was performed. The patient was started on standard corticosteroid therapy and responded well, with complete resolution of the radiological findings.

  11. Plasmacytoid dendritic cells in antiviral immunity and autoimmunity

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Plasmacytoid dendritic cells (pDCs) represent a unique and crucial immune cell population capable of producing large amounts of type I interferons (IFNs) in response to viral infection.The function of pDCs as the professional type I IFN-producing cells is linked to their selective expression of Toll-like receptor 7 (TLR7) and TLR9,which sense viral nucleic acids within the endosomal compartments.Type I IFNs produced by pDCs not only directly inhibit viral replication but also play an essential role in linking the innate and adaptive immune system.The aberrant activation of pDCs by self nucleic acids through TLR signaling and the ongoing production of type I IFNs do occur in some autoimmune diseases.Therefore,pDC may serve as an attractive target for therapeutic manipulations of the immune system to treat viral infectious diseases and autoimmune diseases.

  12. Should There be Concern About Autoimmune Diabetes in Adults? Current Evidence and Controversies.

    Science.gov (United States)

    Østergaard, Jakob Appel; Laugesen, Esben; Leslie, R David

    2016-09-01

    Autoimmune diabetes has a heterogeneous phenotype. Although often considered a condition starting in childhood, a substantial proportion of type 1 diabetes presents in adult life. This holds important implications for our understanding of the factors that modify the rate of progression through the disease prodrome to clinical diabetes and for our management of the disease. When autoimmune diabetes develops in adulthood, insulin treatment is often not required at the time of diagnosis, and this autoimmune non-insulin requiring diabetes is generally termed latent autoimmune diabetes in adults (LADA). Patients with LADA are generally leaner, younger at diabetes onset; have a greater reduction in C-peptide; and have a greater likelihood of insulin treatment as compared with patients with type 2 diabetes. The LADA subset of patients with adult-onset autoimmune diabetes has highlighted many shortcomings in the classification of diabetes and invokes the case for more personalized data analysis in line with the move towards precision medicine. Perhaps most importantly, the issues highlight our persistent failure to engage with the heterogeneity within the most common form of autoimmune diabetes, that is adult-onset type 1 diabetes, both insulin-dependent and initially non-insulin requiring (LADA). This review discusses characteristics of autoimmune diabetes and specifically aims to illustrate the heterogeneity of the disease.

  13. [Assessment of endothelial function in autoimmune diseases].

    Science.gov (United States)

    Benhamou, Y; Bellien, J; Armengol, G; Gomez, E; Richard, V; Lévesque, H; Joannidès, R

    2014-08-01

    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases.

  14. Cacao polyphenols ameliorate autoimmune myocarditis in mice.

    Science.gov (United States)

    Zempo, Hirofumi; Suzuki, Jun-ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2016-04-01

    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress.

  15. The Autoimmune Tautology: An In Silico Approach

    Directory of Open Access Journals (Sweden)

    Ricardo A. Cifuentes

    2012-01-01

    Full Text Available There is genetic evidence of similarities and differences among autoimmune diseases (AIDs that warrants looking at a general panorama of what has been published. Thus, our aim was to determine the main shared genes and to what extent they contribute to building clusters of AIDs. We combined a text-mining approach to build clusters of genetic concept profiles (GCPs from the literature in MedLine with knowledge of protein-protein interactions to confirm if genes in GCP encode proteins that truly interact. We found three clusters in which the genes with the highest contribution encoded proteins that showed strong and specific interactions. After projecting the AIDs on a plane, two clusters could be discerned: Sjögren’s syndrome—systemic lupus erythematosus, and autoimmune thyroid disease—type1 diabetes—rheumatoid arthritis. Our results support the common origin of AIDs and the role of genes involved in apoptosis such as CTLA4, FASLG, and IL10.

  16. Diagnostic criteria for autoimmune pancreatitis in Japan

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Kazuichi Okazaki; Shigeyuki Kawa

    2008-01-01

    Autoimmune pancreatitis (AIP) is a particular type of pancreatitis of presumed autoimmune etiology.Currently, AIP should be diagnosed based on combination of clinical, serological, morphological,and hisLopathological features. When diagnosing AlP,it is most Jmportant to differentiate it from pancreatic cancer. DJagnostic criteria for AIP, proposed by the Japan Pancreas Society in 2002 first in the world,were revised in 2006. The criteria are based on the minimum consensus of AIP and aim to avoid misdiagnosing pancreatic cancer as far as possible,but not for screening AIP. The criteria consist of the following radiological, serological, and histopathological items: (1) radiological imaging showing narrowing of the main pancreatic duct and enlargement of the pancreas, which are characteristic of the disease; (2)laboratory data showing abnormally elevated levels of serum γ-globulin, IgG or IgG4, or the presence of autoantibodies; (3) histopathological examJnation of the pancreas demonstrating marked fibrosis and prominent infiltration of lymphocytes and plasma cells, which is called lymphoplasmacytic sclerosing pancreatitis (LPSP). For a diagnosis of AIP, criterion 1 must be present, together with criterion 2 and/or criterion 3. However, it is necessary to exclude malignant diseases such as pancreatic or biliary cancer.

  17. Comparison of vascular complications between adults latent autoimmune diabetes and type 2 diabetes%成人隐匿性自身免疫糖尿病与2型糖尿病的血管并发症比较

    Institute of Scientific and Technical Information of China (English)

    王晓华; 周智广; 李霞; 黄红光; 李长罗; 林健; 杨琳

    2008-01-01

    Objective To compare the prevalence of microvascular and macrovascular complications between adult latent autoimmune diabetes(LADA)and type 2 diabetic subjects.Methods A cross-sectional study was performed in 203 LADA(GADA positive)and 203 T2DM(GADA negative)subjects matched with age,gender and duration as well as family history of diabetes.Parameters of microvascular(albuminuria、eyeground microscopy or fundus fluorescence photography,electromyogram)and macrovascular complications(electrocardiogram,blood pressure,blood lipid,body mass index)as well as blood sugar were compared.Results ①Microvascular complications:Compared with T2DM,LADA cases showed higher prevalence of diabetic nephropathy(39.9%vs.28.6%,P<0.05)and similar prevalence in diabetic neuropathy and retinopathy(P>0.05).②Macrovascular complications:LADA cases presented lower prevalence of hypertension(38.9%vs.55.7%,P<0.01),lower prevalence of metabolic syndrome (33.0%vs.45.3%,P<0.01=,but similar orevalence of coronarv heart disease (CHD) and erebral infarction(CVD)(P>0.05).Conclusion LADA patients present less metabolic syndrome,hypertension and more diabetic nephropathy compared with T2DM.%目的 探讨成人隐匿性自身免疫糖尿病(LADA)与2型糖尿病(T2DM)血管并发症(包括微血管病变及相关大血管疾病)的差异.方法 比较203例LADA患者与年龄、性别、糖尿病病程及糖尿病家族史匹配的T2DM患者24 h尿白蛋白、眼底检查或荧光造影、心电图、肌电图、血压、血脂、体质指数、空腹血糖、餐后2h血糖、糖化血红蛋白、C肽等方面的差异.结果 ①微血管病变:LADA患者较T2DM患者糖尿病肾病的患病率高(39.9%vs.28.6%,P<0.05),而2组间视网膜病变和周围神经病变的患病率差异无统计学意义(P>0.05).②大血管病变:LADA患者较T2DM患者高血压、代谢综合征的患病率低(38.9%vs.55.7%,P<0.01;33.0%vs.45.3%,P<0.01),2组间冠心病及脑梗死的患病率

  18. The role of melatonin in autoimmune and atopic diseases

    Directory of Open Access Journals (Sweden)

    J.R. Calvo

    2016-04-01

    Full Text Available Melatonin is the main secretory product synthesized and secreted by the pineal gland during the night. Melatonin is a pleitropic molecule with a wide distribution within phylogenetically distant organisms and has a great functional versatility, including the regulation of circadian and seasonal rhythms and antioxidant and anti-inflammatory properties. It also possesses the capacity to modulate immune responses by regulation of the TH1/TH2 balance and cytokine production. Immune system eradicates infecting organisms without serious injury to host tissues, but sometimes these responses are inadequately controlled, giving rise to called hypersensitivity diseases, or inappropriately targeted to host tissues, causing the autoimmune diseases. In clinical medicine, the hypersensitivity diseases include the allergic or atopic diseases and the hallmarks of these diseases are the activation of TH2 cells and the production of IgE antibody. Regarding autoimmunity, at the present time we know that the key events in the development of autoimmunity are a failure or breakdown of the mechanisms normally responsible for maintaining self-tolerance in B lymphocytes, T lymphocytes, or both, the recognition of self-antigens by autoreactive lymphocytes, the activation of these cells to proliferate and differentiate into effector cells, and the tissue injury caused by the effector cells and their products. Melatonin treatment has been investigated in atopic diseases, in several animal models of autoimmune diseases, and has been also evaluated in clinical autoimmune diseases. This review summarizes the role of melatonin in atopic diseases (atopic dermatitis and asthma and in several autoimmune diseases, such as arthritis rheumatoid, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes mellitus, and inflammatory bowel diseases.

  19. Hypergastrinemia and recurrent type 1 gastric carcinoid in a young Indian male: Necessity for antrectomy?

    Institute of Scientific and Technical Information of China (English)

    Viplove Senadhi; Niraj Jani

    2011-01-01

    Carcinoid tumors are the most common neuroendocrine tumors. Gastric carcinoids represent 2% of all carcinoids and 1% of all gastric masses. Due to the widespread use of Esophagogastroduodenoscopy for evaluating a variety of upper gastrointestinal symptoms, the detection of early gastric carcinoids has increased. We highlight an alternative management of a young patient with recurrent type 1 gastric carcinoids with greater than 5 lesions, as well as lesions intermittently greater than 1 cm. Gastric carcinoids have a variable presentation and clinical course that is highly dependent on type. Type 1 gastric carcinoids are usually indolent and have a metastasis rate of less than 2%, even with tumors larger than 2 cm. There are a number of experts as well as organizations that recommend endoscopic resection for all type 1 gastric carcinoid lesions less than 1 cm, with a follow-up every 6-12 mo. They also recommend antrectomy for type 1 gastric carcinoids with greater than 5 lesions, lesions 1 cm or greater, or refractory anemia. However, the American Society of Gastrointestinal Endoscopy guidelines state that type 1 gastric carcinoid surveillance is controversial based on the evidence and could not make an evidence-based position statement on the best treatment modality. Our report illustrates a rare cause of iron deficiency anemia in a young male (without any medical history) due to multiple recurrent gastric carcinoid type 1 lesions in the setting of atrophic gastritis causing hypergastrinemia, and in the absence of a vitamin B12 deficiency. Gastric carcinoid type 1 can present in young males without an autoimmune history, despite the known predilection for women aged 50 to 70 years. Type 1 gastric carcinoids can be managed by endoscopic resection in patients with greater than 5 lesions, even with lesions larger than 1 cm. This course of treatment enabled the avoidance of early antrectomy in our patient, who expressed a preference against more invasive measures at his

  20. Interferons in autoimmune and inflammatory diseases: regulation and roles.

    Science.gov (United States)

    Choubey, Divaker; Moudgil, Kamal D

    2011-12-01

    Several lines of evidence strongly implicate type I interferons (IFN-α and β) and IFN-signaling in the pathogenesis of certain autoimmune inflammatory diseases. Accordingly, genome-wide association studies have identified polymorphisms in the type I IFN-signaling pathways. Other studies also indicate that a feed-forward loop of type I IFN production, which involves sensing of cytoplasmic nucleic acids by sensors, contributes to the development of immunopathology. In addition, a mutually positive regulatory feedback loop between type I IFNs and estrogen receptor-α may contribute to a gender bias, thus resulting in an increased production of type I IFNs and associated immunopathology in women. Increased levels of type I IFNs have numerous immunomodulatory functions for both the innate and adaptive immune responses. Given that the IFN-β also has some anti-inflammatory roles, identifying molecular links among certain genotypes, cytokine profiles, and associated phenotypes in patients with autoimmune inflammatory diseases is likely to improve our understanding of autoimmunity-associated pathogenesis and suboptimal outcomes following standard therapies.

  1. Differences between diffuse and focal autoimmune pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Taku Tabata; Terumi Kamisawa; Kensuke Takuma; Seiichi Hara; Sawako Kuruma; Yoshihiko Inaba

    2012-01-01

    AIM:To investigate differences in clinical features between diffuse-and focal-type autoimmune pancreatitis (AIP).METHODS:Based on radiological findings by computed tomography and/or magnetic resonance imaging,we divided 67 AIP patients into diffuse type (D type)and focal type (F type).We further divided F type into head type (H type) and body and/or tail type (B/T type)according to the location of enlargement.Finally,we classified the 67 AIP patients into three groups:D type,H type and B/F type.We compared the three types of AIP in terms of clinical,laboratory,radiological,functional and histological findings and clinical course.RESULTS:There were 34 patients with D-type,19 with H-type and 14 with B/T-type AIP.Although obstructive jaundice was frequently detected in D-type patients (88%) and H-type patients (68%),no B/T-type patients showed jaundice as an initial symptom (P < 0.001).There were no differences in frequency of abdominal pain,but acute pancreatitis was associated more frequently in B/T-type patients (36%) than in D-type patients (3%) (P =0.017).Serum immunoglobulin G (IgG)4 levels were significantly higher in D-type patients (median 309 mg/dL) than in B/T-type patients (133.5 mg/dL) (P =0.042).Serum amylase levels in B/T-type patients (median:114 IU/L) were significantly greater than in H-type patients (72 IU/L) (P =0.049).Lymphoplasmacytic sclerosing pancreatitis (LPSP) was histologically confirmed in 6 D-type,7 H-type and 4 B/T-type patients; idiopathic duct-centric pancreatitis was observed in no patients.Marked fibrosis and abundant infiltration of CD20-positive B lymphocytes with few IgG4-positive plasma cells were detected in 2 B/T-type patients.Steroid therapy was effective in all 50 patients (31 D type,13 H type and 6 B/T type).Although AIP relapsed during tapering or after stopping steroids in 3 D-type and 3 H-type patients,no patients relapsed in B/T type.During follow-up,radiological features of 6 B/T-type patients were not changed

  2. Accuracy of GastroPanel for the diagnosis of atrophic gastritis

    Science.gov (United States)

    Forné, Montserrat; Barrio, Jesus; De la Coba, Cristobal; González, Begoña; Rivera, Robin; Esteve, Maria; Fernandez-Bañares, Fernando; Madrigal, Beatriz; Gras-Miralles, Beatriz; Perez-Aisa, Angeles; Viver-Pi-Sunyer, Jose M.; Bory, Felipe; Rosinach, Merce; Loras, Carmen; Esteban, Carlos; Santolaria, Santos; Gomollon, Fernando; Valle, Julio; Gisbert, Javier P.

    2014-01-01

    Background It has been suggested that GastroPanel might be a useful tool for the diagnosis of chronic atrophic gastritis (CAG) measuring four biomarkers in blood: basal gastrin-17 (G17), pepsinogen I and II (PGI and PGII), and Helicobacter pylori antibodies. Aim To determine the accuracy of GastroPanel for the diagnosis of CAG. Methods This was a prospective, blinded, multicenter study that included dyspeptic patients. G17, PGI, and PGII were determined by enzyme immunoassays. Three antrum and two corpus biopsies were obtained for standard histological analysis and rapid urease test. Biopsies were analyzed by a single blinded expert pathologist. Results Ninety-one patients were included (77% women, mean age 44 years, 51% H. pylori positive, 17% with CAG). G17 was reduced in patients with antrum CAG (5.4 vs. 13.4 pmol/l; P<0.01) and increased in patients with corpus CAG (11 vs. 24 pmol/l; P<0.05), but its accuracy was only acceptable in the case of corpus localization [area under the receiver operating characteristic curve (AUC), 74%]; PGII difference was almost statistically significant only when testing for corpus atrophy (33 vs. 21 μg/l; P=0.05; AUC=72%). The PGI and PGI/PGII ratio showed no significant differences (AUCs were all unacceptably low). Helicobacter pylori antibody levels were higher in H. pylori-infected patients (251 vs. 109 EIU, P=0.01; AUC=70). The accuracy of GastroPanel for the diagnosis of CAG was as follows: sensitivity 50%; specificity 80%; positive 25% and negative 92% predictive values; and positive 2.4 and negative 0.6 likelihood ratios. Conclusion GastroPanel is not accurate enough for the diagnosis of CAG; thus, its systematic use in clinical practice cannot be recommended. PMID:25014624

  3. What is the Optimal Treatment of Atrophic Scaphoid Non-Union?

    Directory of Open Access Journals (Sweden)

    Alper Cirakli

    2016-09-01

    Full Text Available Aim: To evaluate the efficacy of the treatment method of autogenous iliac wing or radius bone graft and fixation with screw applied to cases of scaphoid non-union. Material and Method: A retrospective evaluation was made of 89 cases between 2000 and 2014. Postoperative measurements were taken of both wrists%u2019 movement with a goniometer and muscle strength was assessed with a dynamometer. Fractures were evaluated radiologically according to the Herbert-Fisher System and the functional results according to the Herbert-Fisher Classification System and the Mayo Clinic Modified Wrist Scoring System. The data were input to the SPSS system and evaluated with the Shapiro-Wilk test. Results: Non-union were on the right side in 47 and the left side in 42 cases. The fracture was seen to be in the waist in 60 cases (67.5%, in the proximal third in 27 cases (30.3% and in the distal third in two cases (2.2%. The mean follow-up period was 16.4 months (range, 5-72 months. Definitive findings of union were observed in 71 cases. The mean time to union was 14.9 weeks (range, 8-40 weeks. Discussion: The grafting procedure applied is an invasive technique but if it is considered that there are negative effects of open surgery on the feeding of the scaphoid bone, then in the treatment of scaphoid non-union which is atrophic non-union, ultimately autogenous bone grafting and screw fixation is a safe and successful method and because of the pain created by an iliac wing graft, radius distal bone graft can be considered more appropriate.

  4. Incidence of chronic atrophic gastritis: systematic review and meta-analysis of follow-up studies.

    Science.gov (United States)

    Adamu, Mariam Abdullahi; Weck, Melanie Nicole; Gao, Lei; Brenner, Hermann

    2010-07-01

    Chronic atrophic gastritis (CAG) is an important precursor lesion of intestinal gastric cancer. As it is typically asymptomatic, epidemiological data on the incidence of CAG are sparse. We aimed to provide an overview of published data on CAG incidence (overall and according to risk factors) from follow-up studies. Articles with information on incidence of CAG published in English until 26th of July 2009 were identified through a systematic MEDLINE and EMBASE search. Data extracted include study characteristics and key findings regarding the incidence of CAG. A meta-analysis was performed on the association between Helicobacter pylori infection and CAG incidence. Overall, data on CAG incidence were available from 14 studies, in 7 studies incidence could be estimated according to H. pylori infection. Most studies were conducted in symptomatic or high risk populations and the maximum number of incident cases was 284. Incidence estimates ranged from 0 to 11% per year and were consistently below 1% in patients not infected with H. pylori. The highest incidence was observed in a special study conducted on ulcer patients treated by proximal gastric vagotomy. Rate ratios for the association between H. pylori infection and CAG incidence ranged from 2.4 to 7.6 with a summary estimate of 5.0 (95% confidence interval: 3.1-8.3). Incidence of CAG is very low in the absence of H. pylori infection. There is a need for more population-based studies to provide comparable estimates of incidence and the impact of risk factors in the development of CAG.

  5. Expression of growth hormone and its receptor in chronic atrophic gastritis and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Si; Qian Cao; Min Gao

    2004-01-01

    AIM: To investigate the growth hormone (GH) and growth hormone receptor (GHR) expression of and its clinical significance in patients with chronic atrophic gastritis (CAG).METHODS:A total of 90 cases were enrolled in the study.Thirty were healthy controls,the other 60 patients were divided into two groups according to the endoscopical and histological diagnosis.Blood samples were drawn in the morning (menarche did not occur during the blood extraction in female patients),gastric mucosa was obtained by endoscopy.Serum GH and gastrice mucosal GHR levels were measured using radioimmunoassay (RIA) and En Vinsion technique.RESULTS:The average GH level was 1.021±0.132μ/L in CAG patients,in controls it was 2.869 0.512μ/L.There was a significant difference between these two groups(P<0.01).The positive rate of GHR in CAG patients was 10%,in controls the rate was 100%.There was a significant difference (P<0.01).There was no significant change of GH level (3.176±0.421μ/L) in patients with gastric carcinoma compared with controls (P>0.05).CONCLUSION:The study shows that levels of GH and GHR expression are low in CAG patients.CAG pathogenesis has a correlation with mucosal nutrient deficiency,decreased levels of GH and GHR have an adverse effect on the repair and regeneration of CAG.There is no significant change of GH in gastric carcinorma patients,GH dose not play a role in the pathogenesis of gastric cancer.

  6. Ageing and autoimmunity.

    Science.gov (United States)

    Fixa, B; Komárková, O; Nozicka, Z

    1975-01-01

    A total of 483 healthy persons from Czechoslovakia, divided into three age groups (below 40, 41-60 and above 61 years) were examined for eight types of autoantibodies (antibodies to epithelial cells and to colloid of thyroid gland, parietal cell antibodies, antibody to intersititial duct cells of parotis and to adrenal cells, anti-nuclear and anti-mitochondrial antibodies, intrinsic factor antibodies). A significantly increased occurrence was observed in the oldest age group, the results being more manifest in women. A conspicious increase was seen particularly in the thyroid antibodies. The results correspond to those of other authors from different geographic areas.

  7. STAT4: genetics, mechanisms, and implications for autoimmunity.

    Science.gov (United States)

    Korman, Benjamin D; Kastner, Daniel L; Gregersen, Peter K; Remmers, Elaine F

    2008-09-01

    Recent advances in genetics and technology have led to breakthroughs in understanding the genes that predispose individuals to autoimmune diseases. A common haplotype of the signal transducer and activator of transcription 4 (STAT4) gene has been shown to be associated with susceptibility to rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome. STAT4 is a transcription factor that transduces interleukin-12, interleukin-23, and type 1 interferon cytokine signals in T cells and monocytes, leading to T-helper type 1 and T-helper type 17 differentiation, monocyte activation, and interferon-gamma production. Although the evidence for this association is very strong and well replicated, the exact mechanism by which polymorphisms in this gene lead to disease remains unknown. In concert with the identification of other disease-associated loci, elucidating how the variant form of STAT4 modulates immune function should lead to an improved understanding of the pathophysiology of autoimmunity.

  8. Historical reflections on autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Ian R Mackay

    2008-01-01

    Autoimmune hepatitis (AIH),initially known as chronic active or active chronic hepatitis (and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody (ANA),smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being (relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.

  9. Autoimmunity: Experimental and clinical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, R.S.; Rose, N.R.

    1986-01-01

    This book contains five parts and a section of poster papers. Each part contains several papers. Some of the papers are: Molecular Genetics and T Cells in Autoimmunity; Gene Conversion: A Mechanism to Explain HLA-D Region and Disease Association; Genetics of the Complement System; Speculation on the Role of Somatic Mutation in the Generation of Anti-DNA Antibodies; and Monoclonal Anti-DNA Antibodies: The Targets and Origins of SLE.

  10. [Autoimmune hepatitis induced by isotretionine].

    Science.gov (United States)

    Guzman Rojas, Patricia; Gallegos Lopez, Roxana; Ciliotta Chehade, Alessandra; Scavino, Yolanda; Morales, Alejandro; Tagle, Martín

    2016-01-01

    We describe a case of a teenage patient with the diagnosis of drug induced autoimmune hepatitis. The patient is a 16 years old female, with the past medical history of Hashimoto’s hypothyroidism controlled with levothyroxine, who started treatment with Isotretionin (®Accutane) 20 mg q/12 hours for a total of 3 months for the treatment of severe acne. The physical examination was within normal limits and the results of the laboratory exams are: Baseline values of ALT 28 U/L, AST 28 U/L. Three months later: AST 756 U/L, ALT 1199U/L, alkaline phosphatase 114 U/L, with normal bilirrubin levels throughout the process. The serology studies were negative for all viral hepatitis; ANA titers were positive (1/160) and igG levels were also elevated. A liver biopsy was performed, and was compatible with the diagnosis of autoimmune hepatitis. Corticosteroid therapy was started with Prednisone 40 mg per day one week after stopping the treatment with isotretionin, observing an improvement in the laboratory values. We describe this case and review the world literature since there are no reported cases of Isotretinoin-induced autoimmune hepatitis.

  11. Autoimmune diseases and HIV infection

    Science.gov (United States)

    Virot, Emilie; Duclos, Antoine; Adelaide, Leopold; Miailhes, Patrick; Hot, Arnaud; Ferry, Tristan; Seve, Pascal

    2017-01-01

    Abstract To describe the clinical manifestations, treatments, prognosis, and prevalence of autoimmune diseases (ADs) in human immunodeficiency virus (HIV)-infected patients. All HIV-infected patients managed in the Infectious Diseases Department of the Lyon University Hospitals, France, between January 2003 and December 2013 and presenting an AD were retrospectively included. Thirty-six ADs were found among 5186 HIV-infected patients which represents a prevalence of 0.69% including immune thrombocytopenic purpura (n = 15), inflammatory myositis (IM) (n = 4), sarcoidosis (n = 4), Guillain–Barré syndrome (GBS) (n = 4), myasthenia gravis (n = 2), Graves’ disease (n = 2), and 1 case of each following conditions: systemic lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis, Hashimoto thyroiditis and autoimmune hemolytic anemia. One patient presented 2 ADs. Thirty patients were known to be HIV-infected when they developed an AD. The AD preceded HIV infection in 2 patients. GBS and HIV infection were diagnosed simultaneously in 3 cases. At AD diagnosis, CD4 T lymphocytes count were higher than 350/mm3 in 63% of patients, between 200 and 350/mm3 in 19% and less than 200/mm3 in 19%. Twenty patients benefited from immunosuppressant treatments, with a good tolerance. ADs during HIV infection are uncommon in this large French cohort. Immune thrombocytopenic purpura, sarcoidosis, IM, and GBS appear to be more frequent than in the general population. Immunosuppressant treatments seem to be effective and well tolerated. PMID:28121924

  12. Th17 Cells in Immunity and Autoimmunity

    Directory of Open Access Journals (Sweden)

    Simone Kennedy Bedoya

    2013-01-01

    Full Text Available Th17 and IL-17 play important roles in the clearance of extracellular bacterial and fungal infections. However, strong evidence also implicates the Th17 lineage in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. The Th17 subset has also been connected with type I diabetes, although whether it plays a role in the pathogenicity of or protection from the disease remains a controversial issue. In this review we have provided a comprehensive overview of Th17 pathogenicity and function, including novel evidence for a protective role of Th17 cells in conjunction with the microbiota gut flora in T1D onset and progression.

  13. Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence.

    Science.gov (United States)

    Choi, In Young; Lee, Changhan; Longo, Valter D

    2017-01-27

    Complex and coordinated signals are necessary to initiate and sustain the activation, proliferation, and differentiation of lymphocytes. These signals, which are known to determine T-cell fate and function, also depend on the metabolic state of the organism. Recent studies indicate that both the type and levels of nutrients can influence the generation, survival and function of lymphocytes and therefore can affect several autoimmune diseases. Here, we review the dysregulation of lymphocytes during autoimmunity and aging, the mechanisms associated with loss of immune function, and how fasting mimicking diets and other dietary interventions affect autoimmunity and immunosenescence.

  14. Long-Lived Plasma Cells in Autoimmunity: Lessons from B-Cell Depleting Therapy

    OpenAIRE

    2013-01-01

    A large number of autoimmune diseases are treated with rituximab, an antibody against CD20 that depletes most of the B cells in the organism. The response to this treatment depends largely on the disease and the type of lymphoid cells involved in the autoimmune process. We recently reported that B-cell depletion in immune thrombocytopenia induced the appearance of pathogenic long-lived plasma cells in the spleen, which were not present before treatment or in non-autoimmune conditions. The spl...

  15. Easily obtainable clinical features increase the diagnostic accuracy for later autoimmune diabetes in adults. An evidence based report

    NARCIS (Netherlands)

    Lutgens, M.W.M.D.; Meijer, M.; Peeters, B.; Poulsen, M.N.F.; Rutten, M.J.; Bots, M.L.; Heijden, van der G.J.M.G.; Soedamah-Muthu, S.S.

    2008-01-01

    Background Latent autoimmune diabetes in adults (LADA) represents a subgroup of diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating autoimmune antibodies. LADA patients may need a different therapeutic approach than the usual type 2 diabetes mellitus. When LADA is inadeq

  16. Translational mini-review series on Th17 cells: are T helper 17 cells really pathogenic in autoimmunity?

    NARCIS (Netherlands)

    Koenders, M.I.; Berg, W.B. van den

    2010-01-01

    In this review the authors discuss the evidence for T helper type 17 (Th17) cells as pathogenic T cells in autoimmunity. Studies with cytokine-deficient mice or blocking of interleukin (IL)-17, IL-21 and IL-22 have resulted in a conflicting data set. Although in the experimental autoimmune encephalo

  17. [Nozological Heterogeneity, Molecular Genetics and Immunology of Autoimmune Diabetes Mellitus].

    Science.gov (United States)

    Dedov, I I; Shestakova, M V; Kuraeva, T L; Titovich, E V; Nikonova, T V

    2015-01-01

    Article is devoted to the review of literature data, and also the analysis of results of own researches concerning genetics, molecular genetics and immunological violations at various forms of the autoimmune diabetes (DM) including classical T1DM, LADA type and an autoimmune polyglandular syndrome of 1 type (APS1). In case of T1DM more than 80% of patients are carriers of one or two strongest predisposing haplotypes: DRB1*04-DQA1*0301-DQB1*0302 and DRB1*03-DQA1*0501-DQB1*0201 designated as DQ2 and DQ8. HLA genes can model a clinical features of disease. In Russian population, the children with diabetes manifestation up to 5-year age has significantly often high risk genotypes (DQ2/ DQ8) and significantly less the low risk genotypes in comparison with children, who had manifestation of T1DMin 10 years and later. The long-term 16-yearsfamily studies showed the maximum frequency of TJDMin high risk group, constantly accruing in process of increase in term of supervision, and in groups of an average and low risk lower and invariable. The highest risk of T1DM manifestation, reaching 90% at 10 years of supervision is defined by existence of HLA high risk genotypes and many antibodies, revealedfrom early age. LADA - the hybridform of autoimmune DM having signs of T1DM and T2DM in the basis. The development of autoimmune process against β-cells can be caused by only gene mutation (APS1). The part of T1DM cases which doesn't have the contributing HLA genes and autoimmune markers in process of studying of the importance of various genes and their biological value can be attributed to new, yet unknown forms of DM.

  18. Fibroblast Cell-Based Therapy for Experimental Autoimmune Diabetes.

    Directory of Open Access Journals (Sweden)

    Reza B Jalili

    Full Text Available Type 1 diabetes (T1D results from autoimmune destruction of insulin producing β cells of the pancreatic islets. Curbing autoimmunity at the initiation of T1D can result in recovery of residual β cells and consequently remission of diabetes. Here we report a cell-based therapy for autoimmune diabetes in non-obese diabetic (NOD mice using dermal fibroblasts. This was achieved by a single injection of fibroblasts, expressing the immunoregulatory molecule indoleamine 2,3 dioxygenase (IDO, into peritoneal cavity of NOD mice shortly after the onset of overt hyperglycemia. Mice were then monitored for reversal of hyperglycemia and changes in inflammatory/regulatory T cell profiles. Blood glucose levels dropped into the normal range in 82% of NOD mice after receiving IDO-expressing fibroblasts while all control mice remained diabetic. We found significantly reduced islet inflammation, increased regulatory T cells, and decreased T helper 17 cells and β cell specific autoreactive CD8+ T cells following IDO cell therapy. We further showed that some of intraperitoneal injected fibroblasts migrated to local lymph nodes and expressed co-inhibitory molecules. These findings suggest that IDO fibroblasts therapy can reinstate self-tolerance and alleviate β cell autoreactivity in NOD mice, resulting in remission of autoimmune diabetes.

  19. Fibroblast Cell-Based Therapy for Experimental Autoimmune Diabetes.

    Science.gov (United States)

    Jalili, Reza B; Zhang, Yun; Hosseini-Tabatabaei, Azadeh; Kilani, Ruhangiz T; Khosravi Maharlooei, Mohsen; Li, Yunyuan; Salimi Elizei, Sanam; Warnock, Garth L; Ghahary, Aziz

    2016-01-01

    Type 1 diabetes (T1D) results from autoimmune destruction of insulin producing β cells of the pancreatic islets. Curbing autoimmunity at the initiation of T1D can result in recovery of residual β cells and consequently remission of diabetes. Here we report a cell-based therapy for autoimmune diabetes in non-obese diabetic (NOD) mice using dermal fibroblasts. This was achieved by a single injection of fibroblasts, expressing the immunoregulatory molecule indoleamine 2,3 dioxygenase (IDO), into peritoneal cavity of NOD mice shortly after the onset of overt hyperglycemia. Mice were then monitored for reversal of hyperglycemia and changes in inflammatory/regulatory T cell profiles. Blood glucose levels dropped into the normal range in 82% of NOD mice after receiving IDO-expressing fibroblasts while all control mice remained diabetic. We found significantly reduced islet inflammation, increased regulatory T cells, and decreased T helper 17 cells and β cell specific autoreactive CD8+ T cells following IDO cell therapy. We further showed that some of intraperitoneal injected fibroblasts migrated to local lymph nodes and expressed co-inhibitory molecules. These findings suggest that IDO fibroblasts therapy can reinstate self-tolerance and alleviate β cell autoreactivity in NOD mice, resulting in remission of autoimmune diabetes.

  20. Toll-Like Receptor Pathways in Autoimmune Diseases.

    Science.gov (United States)

    Chen, Ji-Qing; Szodoray, Peter; Zeher, Margit

    2016-02-01

    Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Several studies suggest that Toll-like receptors (TLRs) play an essential role in the pathogenesis of autoimmune diseases. TLRs belong to the family of pattern recognition receptors (PRRs) that recognize a wide range of pathogen-associated molecular patterns (PAMPs). TLRs are type I transmembrane proteins and located on various cellular membranes. Two main groups have been classified based on their location; the extracelluar group referred to the ones located on the plasma membrane while the intracellular group all located in endosomal compartments responsible for the recognition of nucleic acids. They are released by the host cells and trigger various intracellular pathways which results in the production of proinflammatory cytokines, chemokines, as well as the expression of co-stimulatory molecules to protect against invading microorganisms. In particular, TLR pathway-associated proteins, such as IRAK, TRAF, and SOCS, are often dysregulated in this group of diseases. TLR-associated gene expression profile analysis together with single nucleotide polymorphism (SNP) assessment could be important to explain the pathomechanism driving autoimmune diseases. In this review, we summarize recent findings on TLR pathway regulation in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis.

  1. Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Huey-Kang Sytwu

    2013-05-01

    Full Text Available Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease.

  2. Expanding antigen-specific regulatory networks to treat autoimmunity.

    Science.gov (United States)

    Clemente-Casares, Xavier; Blanco, Jesus; Ambalavanan, Poornima; Yamanouchi, Jun; Singha, Santiswarup; Fandos, Cesar; Tsai, Sue; Wang, Jinguo; Garabatos, Nahir; Izquierdo, Cristina; Agrawal, Smriti; Keough, Michael B; Yong, V Wee; James, Eddie; Moore, Anna; Yang, Yang; Stratmann, Thomas; Serra, Pau; Santamaria, Pere

    2016-02-25

    Regulatory T cells hold promise as targets for therapeutic intervention in autoimmunity, but approaches capable of expanding antigen-specific regulatory T cells in vivo are currently not available. Here we show that systemic delivery of nanoparticles coated with autoimmune-disease-relevant peptides bound to major histocompatibility complex class II (pMHCII) molecules triggers the generation and expansion of antigen-specific regulatory CD4(+) T cell type 1 (TR1)-like cells in different mouse models, including mice humanized with lymphocytes from patients, leading to resolution of established autoimmune phenomena. Ten pMHCII-based nanomedicines show similar biological effects, regardless of genetic background, prevalence of the cognate T-cell population or MHC restriction. These nanomedicines promote the differentiation of disease-primed autoreactive T cells into TR1-like cells, which in turn suppress autoantigen-loaded antigen-presenting cells and drive the differentiation of cognate B cells into disease-suppressing regulatory B cells, without compromising systemic immunity. pMHCII-based nanomedicines thus represent a new class of drugs, potentially useful for treating a broad spectrum of autoimmune conditions in a disease-specific manner.

  3. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis.

    LENUS (Irish Health Repository)

    Fletcher, J M

    2012-02-01

    Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS), which involves autoimmune responses to myelin antigens. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have provided convincing evidence that T cells specific for self-antigens mediate pathology in these diseases. Until recently, T helper type 1 (Th1) cells were thought to be the main effector T cells responsible for the autoimmune inflammation. However more recent studies have highlighted an important pathogenic role for CD4(+) T cells that secrete interleukin (IL)-17, termed Th17, but also IL-17-secreting gammadelta T cells in EAE as well as other autoimmune and chronic inflammatory conditions. This has prompted intensive study of the induction, function and regulation of IL-17-producing T cells in MS and EAE. In this paper, we review the contribution of Th1, Th17, gammadelta, CD8(+) and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes.

  4. [Pulmonary arterial hypertension: a flavor of autoimmunity].

    Science.gov (United States)

    Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2013-01-01

    It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH.

  5. Amplification of autoimmune disease by infection

    OpenAIRE

    Posnett, David N; Yarilin, Dmitry

    2005-01-01

    Reports of infection with certain chronic persistent microbes (herpesviruses or Chlamydiae) in human autoimmune diseases are consistent with the hypothesis that these microbes are reactivated in the setting of immunodeficiency and often target the site of autoimmune inflammation. New experimental animal models demonstrate the principle. A herpesvirus or Chlamydia species can be used to infect mice with induced transient autoimmune diseases. This results in increased disease severity and even ...

  6. Epidemiology of autoimmune diseases in Denmark

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...... diseases and weak across diseases. These data confirm the importance of the autoimmune diseases as a group and suggest that common etiopathologies exist among them...

  7. Production of interleukin (IL)-5 and IL-10 accompanies T helper cell type 1 (Th1) cytokine responses to a major thyroid self-antigen, thyroglobulin, in health and autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Hegedüs, L; Rieneck, Klaus

    2007-01-01

    Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma exert detrimental effects in organ-specific autoimmune disease, while both destructive and protective roles have been demonstrated for interleukin (IL)-10, IL-4 and IL-5. We examined the production of these cytokines by peripheral blood....... Release of IFN-gamma, IL-4 and, notably, IL-5 ensued. Both patient groups exhibited increased TNF-alpha, IL-2, IFN-gamma and IL-10 responses, and PBMC from HT patients secreted lower amounts of IL-5 than male, but not female, controls. Enhanced TNF-alpha production by HT cells also occurred...... in the presence of pooled normal sera, indicating a dependency on intrinsic cellular factors. Conversely, higher production of TNF-alpha and IL-5 occurred in the presence of autologous sera than in the presence of pooled normal sera in both patient groups, indicating a dependency on serum constituents. Complement...

  8. Production of interleukin (IL)-5 and IL-10 accompanies T helper cell type 1 (Th1) cytokine responses to a major thyroid self-antigen, thyroglobulin, in health and autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Nielsen, C H; Hegedüs, L; Rieneck, K;

    2007-01-01

    Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma exert detrimental effects in organ-specific autoimmune disease, while both destructive and protective roles have been demonstrated for interleukin (IL)-10, IL-4 and IL-5. We examined the production of these cytokines by peripheral bloo......-gamma, IL-5 and IL-10 responses were markedly inhibited by partial denaturation of Tg by boiling. We hypothesize that autoantibodies and complement may promote mixed Th1/Th2 cell cytokine responses by enhancing the uptake of autoantigens by antigen-presenting cells....... appeared to promote the production of IL-2 and particularly IL-5, the levels of which were reduced by neutralization of complement by heat- or zymosan treatment. The production of IFN-gamma and IL-2 of the three groups together correlated directly with the serum anti-Tg activity. Moreover, TNF-alpha, IFN...

  9. Microbiota at the crossroads of autoimmunity.

    Science.gov (United States)

    Shamriz, Oded; Mizrahi, Hila; Werbner, Michal; Shoenfeld, Yehuda; Avni, Orly; Koren, Omry

    2016-09-01

    Autoimmune diseases have a multifactorial etiology including genetic and environmental factors. Recently, there has been increased appreciation of the critical involvement of the microbiota in the pathogenesis of autoimmunity, although in many cases, the cause and the consequence are not easy to distinguish. Here, we suggest that many of the known cues affecting the function of the immune system, such as genetics, gender, pregnancy and diet, which are consequently involved in autoimmunity, exert their effects by influencing, at least in part, the microbiota composition and activity. This, in turn, modulates the immune response in a way that increases the risk for autoimmunity in predisposed individuals. We further discuss current microbiota-based therapies.

  10. Modulation of autoimmunity with artificial peptides

    Science.gov (United States)

    La Cava, Antonio

    2010-01-01

    The loss of immune tolerance to self antigens leads to the development of autoimmune responses. Since self antigens are often multiple and/or their sequences may not be known, one approach to restore immune tolerance uses synthetic artificial peptides that interfere or compete with self peptides in the networks of cellular interactions that drive the autoimmune process. This review describes the rationale behind the use of artificial peptides in autoimmunity and their mechanisms of action. Examples of use of artificial peptides in preclinical studies and in the management of human autoimmune diseases are provided. PMID:20807590

  11. Immunological GABAergic interactions and therapeutic applications in autoimmune diseases.

    Science.gov (United States)

    Prud'homme, Gérald J; Glinka, Yelena; Wang, Qinghua

    2015-11-01

    Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. However, it is also produced in other sites; notably by pancreatic β cells and immune cells. The function of GABA in the immune system is at an early stage of study, but it exerts inhibitory effects that are relevant to autoimmune diseases. The study of GABAergic interactions in the immune system has centered on three main aspects: 1) the expression of GABA and the relevant GABAergic molecular machinery; 2) the in vitro response of immune cells; and 3) therapeutic applications in autoimmune diseases. T cells and macrophages can produce GABA, and express all the components necessary for a GABAergic response. There are two types of GABA receptors, but lymphocytes appear to express only type A (GABAAR); a ligand-gated chloride channel. Other immune cells may also express the type B receptor (GABABR); a G-protein coupled receptor. Activation of GABA receptors on T cells and macrophages inhibits responses such as production of inflammatory cytokines. In T cells, GABA blocks the activation-induced calcium signal, and it also inhibits NF-κB activation. In preclinical models, therapeutic application of GABA, or GABAergic (agonistic) drugs, protects against type 1 diabetes (T1D), experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CIA) and contact dermatitis. In addition, GABA exerts anti-apoptotic and proliferative effects on islet β cells, which may be applicable to islet transplantation. Autoimmunity against glutamic acid decarboxylase 65 (GAD65; synthesizes GABA) occurs in T1D. Antigen therapy of T1D with GAD65 or proinsulin in mice has protective effects, which are markedly enhanced by combined GABA therapy. Clinically, autoantibodies against GAD65 and/or GABA receptors play a pathogenic role in several neurological conditions, including stiff person syndrome (SPS), some forms of encephalitis, and autoimmune epilepsy. GABAergic drugs are widely used in

  12. Autoimmunity in X-linked agammaglobulinemia: Kawasaki disease and review of the literature.

    Science.gov (United States)

    Behniafard, Nasrin; Aghamohammadi, Asghar; Abolhassani, Hassan; Pourjabbar, Sarvenaz; Sabouni, Farah; Rezaei, Nima

    2012-02-01

    Although autoimmunity phenotype is surprisingly common in patients with different types of primary antibody deficiency, it is much less frequent in X-linked agammaglobulinemia (XLA). Herein, we report on a 15-month-old boy with XLA who also suffered from Kawasaki disease. The current case presentation is the first report of an association between Kawasaki disease and XLA. XLA could be considered as a special opportunity to understand autoimmunity in the near absence of immunoglobulins.

  13. Concurrent reactive arthritis, Graves’ disease, and warm autoimmune hemolytic anemia: a case report

    OpenAIRE

    Chiang, Elizabeth; Packer, Clifford D

    2009-01-01

    Warm antibody autoimmune hemolytic anemia is due to the presence of warm agglutinins that react with protein antigens on the surface of red blood cells causing premature destruction of circulating red blood cells. We report the first case of concurrent reactive arthritis, Graves’ disease, and autoimmune hemolytic anemia. A 40-year-old man with reactive arthritis, Graves’ disease, type 2 diabetes mellitus, mitral valve prolapse, and Gilbert’s disease presented with a one month history of jaund...

  14. Genome-wide analysis of single nucleotide polymorphisms in patients with atrophic age-related macular degeneration in oldest old Han Chinese.

    Science.gov (United States)

    Zhou, T Q; Guan, H J; Hu, J Y

    2015-12-21

    The aim of this study was to identify disease-associated loci in oldest old Han Chinese with atrophic age-related macular degeneration (AMD). This genome-wide association study (GWAS) only included oldest old (≥95 years old) subjects in Rugao County, China. Thirty atrophic AMD patients and 47 age-matched non-AMD controls were enrolled. The study subjects underwent a complete ophthalmic examination. Genomic DNA was extracted from peripheral blood samples. Single nucleotide polymorphisms (SNPs) were scanned by Genome-Wide Human Mapping SNP 6.0 Arrays and GeneChip Scanner 3000 7G. The results were read and analyzed by the Affymetrix Genotyping Console software. We filtered out the SNPs with a no-call rate ≥10%, MAF P old Han Chinese population. This finding may lead to new strategies for screening of atrophic AMD for Han Chinese.

  15. Juvenile autoimmune hepatitis: Spectrum of the disease

    Institute of Scientific and Technical Information of China (English)

    Giuseppe; Maggiore; Silvia; Nastasio; Marco; Sciveres

    2014-01-01

    Juvenile autoimmune hepatitis(JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific andorgan-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoan-tibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature.

  16. Necroptosis in spontaneously-mutated hematopoietic cells induces autoimmune bone marrow failure in mice

    Science.gov (United States)

    Xin, Junping; Breslin, Peter; Wei, Wei; Li, Jing; Gutierrez, Rafael; Cannova, Joseph; Ni, Allen; Ng, Grace; Schmidt, Rachel; Chen, Haiyan; Parini, Vamsi; Kuo, Paul C.; Kini, Ameet R.; Stiff, Patrick; Zhu, Jiang; Zhang, Jiwang

    2017-01-01

    Acquired aplastic anemia is an autoimmune-mediated bone marrow failure syndrome. The mechanism by which such an autoimmune reaction is initiated is unknown. Whether and how the genetic lesions detected in patients cause autoimmune bone marrow failure have not yet been determined. We found that mice with spontaneous deletion of the TGFβ-activated kinase-1 gene in a small subset of hematopoietic cells developed bone marrow failure which resembled the clinical manifestations of acquired aplastic anemia patients. Bone marrow failure in such mice could be reversed by depletion of CD4+ T lymphocytes or blocked by knockout of interferon-γ, suggesting a Th1-cell-mediated autoimmune mechanism. The onset and progression of bone marrow failure in such mice were significantly accelerated by the inactivation of tumor necrosis factor-α signaling. Tumor necrosis factor-α restricts autoimmune bone marrow failure by inhibiting type-1 T-cell responses and maintaining the function of myeloid-derived suppressor cells. Furthermore, we determined that necroptosis among a small subset of mutant hematopoietic cells is the cause of autoimmune bone marrow failure because such bone marrow failure can be prevented by deletion of receptor interacting protein kinase-3. Our study suggests a novel mechanism to explain the pathogenesis of autoimmune bone marrow failure. PMID:27634200

  17. Autoimmune Hemolytic Anemia and Hodgkin's Disease: An Unusual Pediatric Association

    OpenAIRE

    Maria Miguel Gomes; Tereza Oliva; Armando Pinto

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of lymphoproliferative disorders. AIHA associated with Hodgkin’s disease (HD) is uncommon especially in the pediatric population. The diagnosis of AIHA is usually associated with HD at the time of initial presentation or during the course of disease, but it could precede it by years to months. In adults the association of AIHA and HD is more frequent in advanced stages and in the nodular sclerosis and mixed cellularity type HD. W...

  18. Obesity in autoimmune diseases: not a passive bystander.

    Science.gov (United States)

    Versini, Mathilde; Jeandel, Pierre-Yves; Rosenthal, Eric; Shoenfeld, Yehuda

    2014-09-01

    In the last decades, autoimmune diseases have experienced a dramatic increase in Western countries. The involvement of environmental factors is strongly suspected to explain this rise. Particularly, over the same period, obesity has followed the same outbreak. Since the exciting discovery of the secretory properties of adipose tissue, the relationship between obesity and autoimmunity and the understanding of the underlying mechanisms have become of major interest. Indeed, the fat tissue has been found to produce a wide variety of "adipokines", involved in the regulation of numerous physiological functions, including the immune response. By conducting a systematic literature review, we extracted 329 articles regarding clinical, experimental and pathophysiological data on the relationship between obesity, adipokines - namely leptin, adiponectin, resistin, visfatin - and various immune-mediated conditions, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), psoriasis and psoriatic arthritis (PsA), and thyroid autoimmunity (TAI), especially Hashimoto thyroiditis (HT). The strongest levels of evidence support an increased risk of RA (OR=1.2-3.4), MS (OR=2), psoriasis and PsA (OR=1.48-6.46) in obese subjects. A higher risk of IBD, T1D and TAI is also suggested. Moreover, obesity worsens the course of RA, SLE, IBD, psoriasis and PsA, and impairs the treatment response of RA, IBD, psoriasis and PsA. Extensive clinical data and experimental models demonstrate the involvement of adipokines in the pathogenesis of these autoimmune diseases. Obesity appears to be a major environmental factor contributing to the onset and progression of autoimmune diseases.

  19. Restoring the balance: immunotherapeutic combinations for autoimmune disease

    Directory of Open Access Journals (Sweden)

    Dawn E. Smilek

    2014-05-01

    Full Text Available Autoimmunity occurs when T cells, B cells or both are inappropriately activated, resulting in damage to one or more organ systems. Normally, high-affinity self-reactive T and B cells are eliminated in the thymus and bone marrow through a process known as central immune tolerance. However, low-affinity self-reactive T and B cells escape central tolerance and enter the blood and tissues, where they are kept in check by complex and non-redundant peripheral tolerance mechanisms. Dysfunction or imbalance of the immune system can lead to autoimmunity, and thus elucidation of normal tolerance mechanisms has led to identification of therapeutic targets for treating autoimmune disease. In the past 15 years, a number of disease-modifying monoclonal antibodies and genetically engineered biologic agents targeting the immune system have been approved, notably for the treatment of rheumatoid arthritis, inflammatory bowel disease and psoriasis. Although these agents represent a major advance, effective therapy for other autoimmune conditions, such as type 1 diabetes, remain elusive and will likely require intervention aimed at multiple components of the immune system. To this end, approaches that manipulate cells ex vivo and harness their complex behaviors are being tested in preclinical and clinical settings. In addition, approved biologic agents are being examined in combination with one another and with cell-based therapies. Substantial development and regulatory hurdles must be overcome in order to successfully combine immunotherapeutic biologic agents. Nevertheless, such combinations might ultimately be necessary to control autoimmune disease manifestations and restore the tolerant state.

  20. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice.

    Directory of Open Access Journals (Sweden)

    Marianne Quiding-Järbrink

    Full Text Available BACKGROUND: Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined. METHODOLOGY/PRINCIPAL FINDINGS: By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion. CONCLUSIONS/SIGNIFICANCE: These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis.

  1. Inlay osteotome sinus floor elevation with concentrated growth factor application and simultaneous short implant placement in severely atrophic maxilla

    Science.gov (United States)

    Chen, Yonghui; Cai, Zhiyu; Zheng, Dingguo; Lin, Pei; Cai, Yahua; Hong, Shuxin; Lai, Yiwei; Wu, Dong

    2016-01-01

    Sinus floor elevation with simultaneous implant placement in severely atrophic maxilla is challenging. The aim of this retrospective study was to evaluate the short-term performance of modified osteotome sinus floor elevation (OSFE) with concentrated growth factor (CGF) application and concurrent placement of a short implant in cases with residual bone height (RBH) of 2–4 mm. Twenty-five short implants were installed in 16 patients with mean RBH of 3.23 mm using modified OSFE with CGFs from January 2012 to April 2014. Postoperatively, the implants were clinically evaluated, and vertical bone gain (VBG) was measured using cone beam computed tomography. The mean duration of follow-up was 19.88 months (12–32 months). All the implants were stable with an overall survival rate of 100%. The mean VBG immediately after surgery was 9.21 mm. Six months later, significant reduction of alveolar bone height (2.90 ± 0.22 mm) was found (P  0.05). Within the limits of this study, modified OSFE with CGF application and simultaneous short implant placement could yield predictable clinical results for severely atrophic maxilla with RBH of 2–4 mm. PMID:27250556

  2. Effects of Helicobacter pylori eradication on atrophic gastritis and intestinal metaplasia: A 3-year follow-up study

    Institute of Scientific and Technical Information of China (English)

    Bin Lu; Ming-Tao Chen; Yi-Hong Fan; Yan Liu; Li-Na Meng

    2005-01-01

    AIM: To investigate the effect of H pylori eradication on atrophic gastritis and intestinal metaplasia (IM).METHODS: Two hundred and fifty-nine patients with atrophic gastritis in the antrum were included in the study, 154 patients were selected for H pylori eradication therapy and the remaining 105 patients served as untreated group. Gastroscopy and biopsies were performed both at the beginning and at the end of a 3-year follow-up study. Gastritis was graded according to the updated Sydney system.RESULTS: One hundred and seventy-nine patients completed the follow-up, 92 of them received H pylori eradication therapy and the remaining 87 H pyloriinfected patients were in the untreated group. Chronic gastritis, active gastritis and the grade of atrophy significantly decreased in H pylori eradication group (P<0.01). However, the grade of IM increased in H pylori -infected group (P<0.05).CONCLUSION: H pylori eradication may improve gastric mucosal inflammation, atrophy and prevent the progression of IM.

  3. Autoimmune connective tissue disease: scleroderma.

    Science.gov (United States)

    Wilson, Helen; Vincent, Rachel

    Scleroderma is an umbrella term for a spectrum of rare and complex autoimmune connective tissue diseases, the cause and pathogenesis of which is only partially defined. Scleroderma can be divided into two main subgroups--systemic and localized--but the hallmark of both is skin fibrosis. As yet no drug has been found to be effective in reversing the disease process, however early intervention has been shown to give maximum benefit. Due to the chronic nature of the condition a multidisciplinary approach is essential and the nurse's input from an early stage is vital in supporting the patient to manage both their medical treatment and their activities of daily living.

  4. Tetanic contraction induces enhancement of fatigability and sarcomeric damage in atrophic skeletal muscle and its underlying molecular mechanisms.

    Science.gov (United States)

    Yu, Zhi-Bin

    2013-11-01

    Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigravity muscles of the lower limbs. Besides reducing astronauts' mobility in space and on returning to a gravity environment, the molecular mechanisms for the adaptation of skeletal muscle to unloading also play an important medical role in conditions such as disuse and paralysis. The tail-suspended rat model was used to simulate the effects of weightlessness on skeletal muscles and to induce muscle unloading in the rat hindlimb. Our series studies have shown that the maximum of twitch tension and the twitch duration decreased significantly in the atrophic soleus muscles, the maximal tension of high-frequency tetanic contraction was significantly reduced in 2-week unloaded soleus muscles, however, the fatigability of high-frequency tetanic contraction increased after one week of unloading. The maximal isometric tension of intermittent tetanic contraction at optimal stimulating frequency did not alter in 1- and 2-week unloaded soleus, but significantly decreased in 4-week unloaded soleus. The 1-week unloaded soleus, but not extensor digitorum longus (EDL), was more susceptible to fatigue during intermittent tetanic contraction than the synchronous controls. The changes in K+ channel characteristics may increase the fatigability during high-frequency tetanic contraction in atrophic soleus muscles. High fatigability of intermittent tetanic contraction may be involved in enhanced activity of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and switching from slow to fast isoform of myosin heavy chain, tropomyosin, troponin I and T subunit in atrophic soleus muscles. Unloaded soleus muscle also showed a decreased protein level of neuronal nitric oxide synthase (nNOS), and the reduction in nNOS-derived NO increased frequency of calcium sparks and elevated

  5. Morphological and pathologic changes of experimental chronic atrophic gastritis (CAG) and the regulating mechanism of protein expression in rats

    Institute of Scientific and Technical Information of China (English)

    WANG Liang-jing; CHEN Shu-jie; CHEN Zhe; CAI Jian-ting; SI Jian-min

    2006-01-01

    Objective: To study the pathologic change and molecular regulation in cell proliferation and apoptosis of gastric mucosa in rats with chronic atrophic gastritis (CAG), and evaluate the possible mechanisms. Methods: Rats were administered with 60% alcohol or 2% salicylate sodium, 20 mmol/L deoxycholate sodium and 0.1% ammonia water to establish chronic atrophic gastritis (CAG) models. The gastric specimens were prepared for microscopic view with hematoxylin and eosin (H-E)and alcian blue (A-B) stain. The number of infiltrated inflammatory cells, the thickness of the mucosa gland layer (μm) and the number of gastric glands were calculated. The damage of barrier in mucosa with erosion or ulceration, and the thickness of mucin were examined by scanned electron microscope (SEM). The levels of PGE2, EGF (epiderminal growth factor) and gastrin in the serum were measured with radioimmunoassay or ELISA method. The immunohistochemistry method was used to observe the number of G cells, the expression of protein of EGFR (EGF receptor), C-erbB-2, p53, p16 and bcl-2 in gastric tissue. Results:Under SEM observation, the gastric mucosa was diffused erosion or ulceration and the thickness of mucin was decreased. Compared with normal rats, the grade of inflammatory cell infiltration in CAG rats was elevated, whereas the thickness and number of gastric gland were significantly lower (P<0.05). Compared with normal level of (0.61+0.28) μg/L, EGF in CAG (2.2±0.83) μg/L was significantly higher (P<0.05). The levels of PGE2 and gastrin in serum were significantly lower in CAG rats than that in normal rats (P<0.05). Immunohistochemistry detection showed that the number of G cell in antrum was lower in CAG group (P<0.05). Immuno-stain showed EGFR protein expression in the basal and bilateral membrane, and the cytoplasma in atrophic gastric gland, while negative expression was observed in normal gastric epithelial cells. Positive staining of p53 and p16 protein was localized in

  6. Autoimmune hepatitis in India: profile of an uncommon disease

    Directory of Open Access Journals (Sweden)

    Baba Chalamalasetty S

    2005-08-01

    , rheumatoid arthritis 2, Sjogren's syndrome 1 and autoimmune polyglandular syndrome III in 1. Viral markers were positive in two patients, one presenting as acute hepatitis and HEV-IgM positive and another anti-HCV positive. Conclusion In India, autoimmune hepatitis is uncommon and usually presents with chronic hepatitis or cirrhosis, acute hepatitis being less common. Age at presentation was earlier but clinical parameters and associated autoimmune diseases were similar to that reported from the west. Primary biliary cirrhosis is rare. Type II AIH was not observed.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  8. Autoimmune hepatitis and juvenile systemic lupus erythematosus

    NARCIS (Netherlands)

    Deen, M. E. J.; Porta, G.; Fiorot, F. J.; Campos, L. M. A.; Sallum, A. M. E.; Silva, C. A. A.

    2009-01-01

    Juvenile systemic lupus erythematosus (JSLE) and autoimmune hepatitis (AIH) are both autoimmune disorders that are rare in children and have a widespread clinical manifestation. A few case reports have shown a JSLE-AIH associated disorder. To our knowledge, this is the first study that simultaneousl

  9. Chronic autoimmune urticaria : Where we stand ?

    Directory of Open Access Journals (Sweden)

    Goh C

    2009-01-01

    Full Text Available It is well-recognized that 30-40% of chronic idiopathic urticaria is autoimmune in nature. Chronic autoimmune urticaria is caused by anti-FcåRI and less frequently, by anti-IgE autoantibodies that lead to mast cell and basophil activation, thereby giving rise to the release of histamine and other proinflammatory mediators. Activation of the classical complement pathway and formation of C5a are important in dermal mast cell activation. C5a is also a neutrophil and eosinophil chemoattractant. Chronic autoimmune urticaria has been found to be associated with autoimmune thyroid disease. The autologous serum skin test is used as a screening test for chronic autoimmune urticaria and has a sensitivity and specificity of about 70 and 80%, respectively. The current gold standard diagnostic test is the basophil histamine release assay. The treatment of chronic autoimmune urticaria, as in chronic idiopathic urticaria, is with H1 antihistamines. Oral corticosteroids may be used during acute flares. Refractory cases have been shown to respond to cyclosporine and other immunomodulators. The prevalence of chronic autoimmune urticaria in Singapore is similar to that reported in Western countries at about 42%. The presence of thyroid autoimmunity appears to be higher than reported, with 22.5% of patients with chronic idiopathic urticaria here, exhibiting presence of thyroid autoantibodies.

  10. Autoimmune pancreatitis exhibiting multiple mass lesions.

    Science.gov (United States)

    Shiokawa, Masahiro; Kodama, Yuzo; Hiramatsu, Yukiko; Kurita, Akira; Sawai, Yugo; Uza, Norimitsu; Watanabe, Tomohiro; Chiba, Tsutomu

    2011-09-01

    Our case is a first report of autoimmune pancreatitis with multiple masses within the pancreas which was pathologically diagnosed by endoscopic ultrasound-guided fine needle aspiration and treated by steroid. The masses disappeared by steroid therapy. Our case is informative to know that autoimmune pancreatitis sometimes exhibits multiple masses within the pancreas and to diagnose it without unnecessary surgery.

  11. Autoimmune Pancreatitis Exhibiting Multiple Mass Lesions

    Directory of Open Access Journals (Sweden)

    Masahiro Shiokawa

    2011-09-01

    Full Text Available Our case is a first report of autoimmune pancreatitis with multiple masses within the pancreas which was pathologically diagnosed by endoscopic ultrasound-guided fine needle aspiration and treated by steroid. The masses disappeared by steroid therapy. Our case is informative to know that autoimmune pancreatitis sometimes exhibits multiple masses within the pancreas and to diagnose it without unnecessary surgery.

  12. Gender and autoimmune comorbidity in multiple sclerosis

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

  13. Cardiovascular Involvement in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Jenny Amaya-Amaya

    2014-01-01

    Full Text Available Autoimmune diseases (AD represent a broad spectrum of chronic conditions that may afflict specific target organs or multiple systems with a significant burden on quality of life. These conditions have common mechanisms including genetic and epigenetics factors, gender disparity, environmental triggers, pathophysiological abnormalities, and certain subphenotypes. Atherosclerosis (AT was once considered to be a degenerative disease that was an inevitable consequence of aging. However, research in the last three decades has shown that AT is not degenerative or inevitable. It is an autoimmune-inflammatory disease associated with infectious and inflammatory factors characterized by lipoprotein metabolism alteration that leads to immune system activation with the consequent proliferation of smooth muscle cells, narrowing arteries, and atheroma formation. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and progression of AT. Several risk factors, known as classic risk factors, have been described. Interestingly, the excessive cardiovascular events observed in patients with ADs are not fully explained by these factors. Several novel risk factors contribute to the development of premature vascular damage. In this review, we discuss our current understanding of how traditional and nontraditional risk factors contribute to pathogenesis of CVD in AD.

  14. Cystic Lesions in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Macarena Gompertz

    2015-11-01

    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.

  15. Susceptibility Genes in Thyroid Autoimmunity

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    Yoshiyuki Ban

    2005-01-01

    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.

  16. [Autoimmune Diseases of Digestive System].

    Science.gov (United States)

    Ivashkinl, V T; Sheptulina, A F; Raĭkhelson, K L; Losik, E A; Ivashkin, K V; Okhlobystin, A V; Baranskaia, E K; Polouvektova, E A; Shifrin, O S

    2015-01-01

    Autoimmune diseases of digestive system refer to pathological conditions, caused by autoimmune mechanisms, and their etiology remains unknown. This is a group of relatively rare diseases, however, during the last years a marked tendency towards the raise in incidence andprevalence is observed, which led to an increase in number of clinical investigations on etiology, pathogenesis, and, accordingly, development of new diagnostic methods and therapies. Results of such trials shown, for example, that the pathogenesis of chronic cholestatic liver diseases is associated with nuclear receptors function, while the main etiological and pathogenic factor of inflammatory bowel diseases represents gut microbiota. Despite new achievements in autoinmune diseases of digestive system research, therapies are low effective and are accompanied by a huge number of adverse events. The fact that these diseases may lead to malignant tumors is also worth noting. For example, patients with primary sclerosing cholangitis have a 160 times higher risk of cholangiocellular carcinoma, while 10-14% ofpatients with celiac disease may develop malignancies of esophagus, small and large intestine. Thus, these diseases require further investigation with a purpose of more accurate diagnostic methods for the detection of disease at early stages and new effective and safe therapies development.

  17. Hepatitis A vaccine associated with autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    PA Berry; G Smith-Laing

    2007-01-01

    To describe a case of probable relapsing autoimmune hepatitis associated with vaccination against hepatitis A virus (HAV). A case report and review of literature were written concerning autoimmune hepatitis in association with hepatitis A and other hepatotropic viruses. Soon after the administration of formalin-inactivated hepatitis A vaccine, a man who had recently recovered from an uncharacterized but self-limiting hepatitic illness,experienced a severe deterioration (AST 1687 U/L, INR 1.4). Anti-nuclear antibodies were detectable, and liver biopsy was compatible with autoimmune hepatitis. The observation supports the role of HAV as a trigger of autoimmune hepatitis. Studies in helper T-cell activity and antibody expression against hepatic proteins in the context of hepatitis A infection are summarized, and the concept of molecular mimicry with regard to other forms of viral hepatitis and autoimmunity is briefly explored.

  18. Autoimmune diseases in women with Turner's syndrome

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...

  19. Recurrence of autoimmune liver diseases after livertransplantation

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Liver transplantation (LT) is the most effective treatmentmodality for end stage liver disease caused by manyetiologies including autoimmune processes. That said,the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis (PBC), but not forprimary sclerosing cholangitis (PSC), has decreasedover the years due to the availability of effective medicaltreatment. Autoimmune liver diseases have superiortransplant outcomes than those of other etiologies. WhileAIH and PBC can recur after LT, recurrence is of limitedclinical significance in most, but not all cases. RecurrentPSC, however, often progresses over years to a stagerequiring re-transplantation. The exact incidence andthe predisposing factors of disease recurrence remaindebated. Better understanding of the pathogenesis andthe risk factors of recurrent autoimmune liver diseasesis required to develop preventive measures. In thisreview, we discuss the current knowledge of incidence,diagnosis, risk factors, clinical course, and treatmentof recurrent autoimmune liver disease (AIH, PBC, PSC)following LT.

  20. The immunobiology of Campylobacter jejuni: Innate immunity and autoimmune diseases.

    Science.gov (United States)

    Phongsisay, Vongsavanh

    2016-04-01

    The Gram-negative bacterium Campylobacter jejuni causes gastroenteritis and Guillain-Barré syndrome in humans. Recent advances in the immunobiology of C. jejuni have been made. This review summarizes C. jejuni-binding innate receptors and highlights the role of innate immunity in autoimmune diseases. This human pathogen produces a variety of glycoconjugates, including human ganglioside-like determinants and multiple activators of Toll-like receptors (TLRs). Furthermore, C. jejuni targets MyD88, NLRP3 inflammasome, TIR-domain-containing adapter-inducing interferon-β (TRIF), sialic acid-binding immunoglobulin-like lectins (Siglecs), macrophage galactose-type lectin (MGL), and immunoglobulin-like receptors (TREM2, LMIR5/CD300b). The roles of these innate receptors and signaling molecules have been extensively studied. MyD88-mediated TLR activation or inflammasome-dependent IL-1β secretion is essential for autoimmune induction. TRIF mediates the production of type I interferons that promote humoral immune responses and immunoglobulin class-switching. Siglec-1 and Siglec-7 interact directly with gangliosides. Siglec-1 activation enhances phagocytosis and inflammatory responses. MGL internalizes GalNAc-containing glycoconjugates. TREM2 is well-known for its role in phagocytosis. LMIR5 recognizes C. jejuni components and endogenous sulfoglycolipids. Several lines of evidence from animal models of autoimmune diseases suggest that simultaneous activation of innate immunity in the presence of autoreactive lymphocytes or antigen mimicry may link C. jejuni to immunopathology.

  1. [The role of hereditary and environmental factors in autoimmune thyroid diseases].

    Science.gov (United States)

    Balázs, Csaba

    2012-07-01

    Autoimmune thyroid diseases are the most common organ-specific autoimmune disorders affecting 5% to 10% of the population in Western countries. The clinical presentation varies from hyperthyroidism in Graves' disease to hypothyroidism in Hashimoto's thyroiditis. While the exact etiology of thyroid autoimmunity is not known, the interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. The identified autoimmune thyroid disease susceptibility genes include immune-modulating genes, such as the major histocompatibility complex, and thyroid-specific genes, including TSH receptor, thyroglobulin and thyroid peroxidase. The majority of the anti-TSH-receptor antibodies have a stimulating capacity and are responsible for hyperthyroidism. The anti-thyroglobulin- and anti-thyroid peroxidase antibodies belonging to the catalytic type of antibodies destroy the thyrocytes resulting in hypothyroidism. The appearance of anti-thyroid peroxidase antibodies precedes the induction of thyroiditis and the manifestation of hypothyroidism. The molecular analysis of thyroglobulin gene polymorphism is important in the mechanism of autoimmune thyroiditis. The autoantigen presentation by major histocompatibility complex molecules is a key point of the autoimmune mechanism. It has been shown that a HLA-DR variant containing arginine at position 74 of the DRβ1 chain confers a strong genetic susceptibility to autoimmune thyroid diseases, Graves' disease and Hashimoto's thyroiditis, while glutamine at position DRβ1-74 is protective. Human thyroglobulin 2098 peptide represents a strong and specific DRβ1-Arg74 binder, while a non-binding control peptide, thyroglobulin 2766 fails to induce this response. Moreover, thyroglobulin 2098 stimulated T-cells from individuals who were positive for thyroglobulin antibodies, demonstrating that thyroglobulin 2098 is an immunogenic peptide capable of being

  2. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...... was associated with each of the three diseases. Although there was a significant overlap, most loci only occurred in one of the studied disease. Remarkably, within each disease, there was a statistical interaction (synergy) between two loci. Additional synergy between retroviral loci and human lymphocyte...

  3. Does genomic imprinting play a role in autoimmunity?

    Science.gov (United States)

    Camprubí, Cristina; Monk, David

    2011-01-01

    In the 19th century Gregor Mendel defined the laws of genetic inheritance by crossing different types of peas. From these results arose his principle of equivalence: the gene will have the same behaviour whether it is inherited from the mother or the father. Today, several key exceptions to this principle are known, for example sex-linked traits and genes in the mitochondrial genome, whose inheritance patterns are referred to as 'non mendelian'. A third, important exception in mammals is that of genomic imprinting, where transcripts are expressed in a monoallelic fashion from only the maternal or the paternal chromosome. In this chapter, we discuss how parent-of-origin effects and genomic imprinting may play a role in autoimmunity and speculate how imprinted miRNAs may influence the expression of many target autoimmune associated genes.

  4. [Metabolic disorders and nutritional status in autoimmune thyroid diseases].

    Science.gov (United States)

    Kawicka, Anna; Regulska-Ilow, Bożena; Regulska-Ilow, Bożena

    2015-01-02

    In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs) are caused by an abnormal immune response to autoantigens present in the thyroid gland - they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto's disease. Hashimoto's thyroiditis can be the main cause of primary hypothyroidism of the thyroid gland. Anthropometric, biochemical and physicochemical parameters are used to assess the nutritional status during the diagnosis and treatment of thyroid diseases. Patients with hypothyroidism are often obese, whereas patients with hyperthyroidism are often afflicted with rapid weight loss. The consequence of obesity is a change of the thyroid hormones' activity; however, weight reduction leads to their normalization. The activity and metabolic rate of thyroid hormones are modifiable. ATDs are associated with abnormalities of glucose metabolism and thus increased risk of developing diabetes mellitus type 1 and type 2. Celiac disease (CD) also increases the risk of developing other autoimmune diseases. Malnutrition or the presence of numerous nutritional deficiencies in a patient's body can be the cause of thyroid disorders. Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may impair the function of the thyroid gland. Other nutrient deficiencies usually observed in patients suffering from ATD are: protein deficiencies, vitamin deficiencies (A, C, B6, B5, B1) and mineral deficiencies (phosphorus, magnesium, potassium, sodium, chromium). Proper diet helps to reduce the symptoms of the disease, maintains a healthy weight and prevents the occurrence of malnutrition. This article presents an overview of selected documented studies and scientific reports on the relationship of metabolic

  5. Chemical reconstruction of skin scars therapy using 100% trichloroacetic acid in the treatment of atrophic facial post varicella scars: A pilot study

    Directory of Open Access Journals (Sweden)

    Nidheesh Agarwal

    2013-01-01

    Full Text Available Context: Chickenpox (varicella is a common viral disease caused by Varicella zoster virus. Facial atrophic scars after varicella infection are not uncommon and pose a cosmetic problem. Like atrophic scars of other aetiologies, they are a difficult condition to treat. There are not enough references in the literature regarding efficient treatment of post varicella scars. High strength Trichloroacetic acid (TCA, which is known to cause dermal collagen remodelling, was used to treat varicella scars in the present study. Aims: The study was undertaken to assess the efficiency of Chemical Reconstruction of Skin Scars (CROSS technique using 100% TCA in the treatment of atrophic facial post varicella scars. Settings and Design: Open label, pilot study. Materials and Methods: A total of 16 patients with atrophic facial post varicella scars were treated by focal application of 100% TCA solution by pressing down upon the scar surface by a toothpick (CROSS technique. Total 4 sittings were given at 2 weekly intervals and the results evaluated after 3 months of follow-up. Statistical analysis was carried out using Fischer′s exact t-test. Results: All of the 13 patients who completed the study showed good clinical improvement, with 69% patients grading the response as excellent (>75% improvement, whereas the rest 31% patients reporting good (51-75% improvement. No significant complications were seen in any patient. Conclusions: CROSS technique using 100% TCA is a safe, cheap and effective therapy for the treatment of post varicella scars.

  6. Rett syndrome: An autoimmune disease?

    Science.gov (United States)

    De Felice, Claudio; Leoncini, Silvia; Signorini, Cinzia; Cortelazzo, Alessio; Rovero, Paolo; Durand, Thierry; Ciccoli, Lucia; Papini, Anna Maria; Hayek, Joussef

    2016-04-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disease, previously included into the autistic spectrum disorders, affecting almost exclusively females (frequency 1:10,000). RTT leads to intellective deficit, purposeful hands use loss and late major motor impairment besides featuring breathing disorders, epilepsy and increased risk of sudden death. The condition is caused in up to 95% of the cases by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Our group has shown a number of previously unrecognized features, such as systemic redox imbalance, chronic inflammatory status, respiratory bronchiolitis-associated interstitial lung disease-like lung disease, and erythrocyte morphology changes. While evidence on an intimate involvement of MeCP2 in the immune response is cumulating, we have recently shown a cytokine dysregulation in RTT. Increasing evidence on the relationship between MeCP2 and an immune dysfunction is reported, with, apparently, a link between MECP2 gene polymorphisms and autoimmune diseases, including primary Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. Antineuronal (i.e., brain proteins) antibodies have been shown in RTT. Recently, high levels of anti-N-glucosylation (N-Glc) IgM serum autoantibodies [i.e., anti-CSF114(N-Glc) IgMs] have been detected by our group in a statistically significant number of RTT patients. In the current review, the Authors explore the current evidence, either in favor or against, the presence of an autoimmune component in RTT.

  7. Experimental drugs for treatment of autoimmune myocarditis

    Institute of Scientific and Technical Information of China (English)

    Han Lina; Guo Shuli; Wang Yutang; Yang Liming; Liu Siyu

    2014-01-01

    Objective To review the experimental drugs for the treatment of autoimmune myocarditis.Data sources The literatures published in English about different kinds of experimental drugs based on different therapeutic mechanisms for the treatment of autoimmune myocarditis were obtained from PubMed from 2002 to 2013.Study selection Original articles regarding the experimental drugs for treatment of autoimmune myocarditis were selected.Results This study summarized the effects of the experimental drugs for the treatment of autoimmune myocarditis,such as immunomodulators and immunosuppressants,antibiotics,Chinese medicinal herbs,cardiovascular diseases treatment drugs,etc.These drugs can significantly attenuate autoimmune myocarditis-induced inflammation and fibrosis,alleviate autoimmune myocarditis-triggered overt lymphocyte proliferation,and meanwhile reduce Th1 cytokines (IFN-γ and IL-2) and increase Th2 cytokines (IL-4 and IL-10).Conclusion This study summarized recent advances in autoimmune myocarditis treatment and further proposes that traditional Chinese medicine and immune regulators will play important roles in the future.

  8. Criteria for Environmentally Associated Autoimmune Diseases

    Science.gov (United States)

    Pollard, K. Michael; Parks, Christine G.; Germolec, Dori R.; Leung, Patrick S.C.; Selmi, Carlo; Humble, Michael C.; Rose, Noel R.

    2012-01-01

    Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future. PMID:22771005

  9. Diagnosis and classification of autoimmune orchitis.

    Science.gov (United States)

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

    2014-01-01

    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.

  10. Cutting-edge issues in autoimmune orchitis.

    Science.gov (United States)

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

    2012-04-01

    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.

  11. Renal Cell Carcinoma Mimicking Igg4-Related Pseudotumor in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Khan

    2014-09-01

    Full Text Available Context Autoimmune pancreatitis is classified into two distinct clinical profiles. Care report Type 1 autoimmunepancreatitis (AIP is considered to be a manifestation of a novel clinicopathological entity called IgG4 related sclerosingdisease, diagnosed using the Mayo Clinic HISORt criteria. Extra-pancreatic manifestations can include involvement of bileducts, salivary gland, lung nodules, thyroiditis, tubulointerstitial nephritis, renal masses, and retroperitoneal fibrosis. Type2 autoimmune pancreatitis on the other hand is confirmed by histologically seen duct centric pancreatitis without elevationof IgG4 or involvement of other organs. In type 1 autoimmune pancreatitis, extrapancreatic manifestations like bile ductstrictures, tubulointerstitial nephritis, renal nodules, retroperitoneal fibrosis respond to steroid therapy. Conclusion Wepresent a case of type 1 autoimmune pancreatitis in which the renal mass did not respond to steroid therapy and was later on found to be renal cell carcinoma. To the best of our knowledge this is only the third reported case of autoimmune pancreatitis in which the patient had renal cell carcinoma. Our case highlights the importance of close follow up of lesions that do not respond to steroid treatment which in this case proved to be renal cell cancer.

  12. Etiology of Organ-Specific Autoimmunity: Basic Research and Clinical Implications in IBD

    Directory of Open Access Journals (Sweden)

    George S Eisenbarth

    1996-01-01

    Full Text Available Autoimmunity develops in the setting of genetic susceptibility and can be monogenic (eg, autoimmune polyendocrine syndrome type I with Addison’s disease, mucocutaneous candidiasis and hypoparathyroidism, which is autosomal recessive with the causative gene on the tip of chromosome 21 or polygenic (usually with important alleles within the major histocompatibility complex [eg, type I diabetes]. In addition to genetic susceptibility, many autoimmune disorders can be classified into etiological categories (oncogenic, drug-induced, diet-induced, infectious or idiopathic. For most autoimmune disorders there are multiple target autoantigens and, for type I diabetes, a combinatorial approach (eg, expression of at least two autoantibodies of insulin, glutamic acid decarboxylase and/or ICA512/IA-2 is the best predictor of diabetes risk. Finally, antigen-specific therapies hold promise for the prevention and therapy of autoimmunity, eg, parenteral or oral therapy with insulin delays or prevents type I diabetes in animal models, and a small pilot trial of parenteral insulin in humans suggests that such therapy may similarly prevent diabetes in humans.

  13. Common immunogenetic profile in children with multiple autoimmune diseases: the signature of HLA-DQ pleiotropic genes.

    Science.gov (United States)

    Larizza, Daniela; Calcaterra, Valeria; Klersy, Catherine; Badulli, Carla; Caramagna, Claudia; Ricci, Antonio; Brambilla, Paola; Salvaneschi, Laura; Martinetti, Miryam

    2012-09-01

    Type 1 diabetes mellitus (T1DM), celiac disease (CD) and autoimmune thyroid disease (ATD) are autoimmune conditions relatively common in paediatric age and frequently occur in association in the same subject. This event is not by chance and requires an explanation. Here, we studied the distribution of HLA-DQ αβ heterodimers in 334 Italian children with T1DM, ATD and CD alone or in association and in 224 Italian healthy controls. In particular, 164 patients had T1DM (133 alone, 20+ATD, 7+CD and 4+CD+ATD), 118 had ATD (110 alone, 8+CD) and 52 had CD (40 alone, 11+ATD and 1+T1DM). 51 patients suffered from multiple autoimmune diseases. The risk for multiple autoimmune diseases was significantly associated with the increased number of HLA-DQ markers of susceptibility for both T1DM (p = 0.003) and CD (p = 0.006). The presence of one or more diabetogenic DQ molecules significantly increased the probability of developing not only T1DM (p autoimmune diseases although with a different risk according to the number and type of susceptible HLA-DQ heterodimers as reported in the algorithm proposed here. It is likely that combinations of DQA1 and DQB1 alleles are the real culprits of the progression towards multiple autoimmune diseases and HLA-DQ genomic typing will improve the capability to predict associated autoimmune diseases in infancy.

  14. Presence of Autoimmune Antibody in Chikungunya Infection

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    Wirach Maek-a-nantawat

    2009-01-01

    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.

  15. Lymphocyte Activation Gene-3 (LAG-3 negatively regulates environmentally-induced autoimmunity.

    Directory of Open Access Journals (Sweden)

    Vibha Jha

    Full Text Available Environmental factors including drugs, mineral oils and heavy metals such as lead, gold and mercury are triggers of autoimmune diseases in animal models or even in occupationally exposed humans. After exposure to subtoxic levels of mercury (Hg, genetically susceptible strains of mice develop an autoimmune disease characterized by the production of highly specific anti-nucleolar autoantibodies, hyperglobulinemia and nephritis. However, mice can be tolerized to the disease by a single low dose administration of Hg. Lymphocyte Activation Gene-3 (LAG-3 is a CD4-related, MHC-class II binding molecule expressed on activated T cells and NK cells which maintains lymphocyte homeostatic balance via various inhibitory mechanisms. In our model, administration of anti-LAG-3 monoclonal antibody broke tolerance to Hg resulting in autoantibody production and an increase in serum IgE level. In addition, LAG-3-deficient B6.SJL mice not only had increased susceptibility to Hg-induced autoimmunity but were also unresponsive to tolerance induction. Conversely, adoptive transfer of wild-type CD4(+ T cells was able to partially rescue LAG-3-deficient mice from the autoimmune disease. Further, in LAG-3-deficient mice, mercury elicited higher amounts of IL-6, IL-4 and IFN-γ, cytokines known to play a critical role in mercury-induced autoimmunity. Therefore, we conclude that LAG-3 exerts an important regulatory effect on autoimmunity elicited by a common environmental pollutant.

  16. The use of stem cells for the treatment of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    S.B. Rosa

    2007-12-01

    Full Text Available Autoimmune diseases constitute a heterogeneous group of conditions commonly treated with anti-inflammatory, immunosuppressant and immunomodulating drugs, with satisfactory results in most cases. Nevertheless, some patients become resistant to conventional therapy. The use of high doses of drugs in such cases results in the need for bone marrow reconstitution, a situation which has stimulated research into the use of hematopoietic stem cells in autoimmune disease therapy. Stem cell transplantation in such diseases aims to destroy the self-reacting immune cells and produce a new functional immune system, as well as substitute cells for tissue damaged in the course of the disease. Significant results, such as the reestablishment of tolerance and a decrease in the recurrence of autoimmune disease, have been reported following stem cell transplantation in patients with autoimmune disease in Brazil and throughout the world. These results suggest that stem cell transplantation has the potential to become an important therapeutic approach to the treatment of various autoimmune diseases including rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, multiple sclerosis, systemic sclerosis, Crohn's disease, autoimmune blood cytopenias, and type I diabetes mellitus.

  17. Clinical characteristics of patients with lymphoproliferative neoplasms in the setting of systemic autoimmune diseases.

    Science.gov (United States)

    Suvajdzic, Nada; Djurdjevic, Predrag; Todorovic, Milena; Perunicic, Maja; Stojanović, Roksanda; Novkovic, Aleksandra; Mihaljevic, Biljana

    2012-09-01

    Clinical features of 40 lymphoproliferative neoplasm patients in the setting of systemic autoimmune diseases managed in the Clinic of Hematology during 1994-2006 were analyzed retrospectively. The classification of systemic autoimmune disease patients was as follows: 15 systemic lupus erythematosus--SLE, 11 rheumatoid arthritis--RA, 12 Sjögren's syndrome--SS, 1 scleroderma, and 1 dermatomyositis. Patients comprised 31 women and 9 men of mean age 55 years (range 33-76). Systemic autoimmune diseases preceeded the development of lymphoproliferative neoplasms in 37/40 (92.5%) patients. Mean latency period between the onset of systemic autoimmune diseases and lymphoproliferative neoplasms occurrence was significantly longer in RA (113 months) than in SLE (75 months) and SS patients (65 months)--P autoimmune diseases type or antirheumatic treatment P > 0.05. Our findings are in line with earlier reports showing a high proportion of patients with advanced disease, constitutional symptoms, extranodal manifestations, high grade histology, and low OS in the systemic autoimmune diseases setting.

  18. Autoimmune pancreatitis: Functional and morphological recovery after steroid therapy

    Institute of Scientific and Technical Information of China (English)

    László Czakó; (E)va Hegyk(o)zi; Attila Pálinkás; János Lonovics

    2006-01-01

    Autoimmune pancreatitis, a recently recognized type of chronic pancreatitis, is not rare in Japan, but reports of it elsewhere are relatively uncommon. We report the first preoperatively diagnosed case of autoimmune pancreatitis in Hungary, which responded well to steroid treatment and provided radiographic and functional evidence of this improvement. A 62-year-old female presented with a 4-month history of recurrent epigastric pain and a 5-kg weight loss. The oral glucose tolerance test (OGTT) indicated diabetes mellitus and the result of the fecal elastase test was abnormal. Ultrasonography (US) and the CT scan demonstrated a diffusely enlarged pancreas, and endoscopic retrograde cholangiopancreatography (ERCP) an irregular main pancreatic duct with long strictures in the head and tail. Autoimmune pancreatitis was diagnosed. The patient was started on 32 mg prednisolone daily. After 4 wk, the OGTT and faecal elastase test results had normalized. The repeated US and CT scan revealed a marked improvement of the diffuse pancreatic swelling, while on repeated ERCP, the main pancreatic duct narrowing was seen to be ameliorated. It is important to be aware of this disease and its diagnosis, because AIP can clinically resemble pancreatobiliary malignancies, or chronic or acute pancreatitis. However,in contrast with chronic pancreatitis, its symptoms and morphologic and laboratory alterations are completely reversed by oral steroid therapy.

  19. Origin of B-Cell Neoplasms in Autoimmune Disease.

    Directory of Open Access Journals (Sweden)

    Kari Hemminki

    Full Text Available Autoimmune diseases (ADs are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis. By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation.

  20. Autoimmune Hemolytic Anemia in Children: Mayo Clinic Experience.

    Science.gov (United States)

    Sankaran, Janani; Rodriguez, Vilmarie; Jacob, Eapen K; Kreuter, Justin D; Go, Ronald S

    2016-04-01

    We studied 35 pediatric patients with autoimmune hemolytic anemia seen at Mayo Clinic from 1994 to 2014. The median age was 10.0 years and 65.7% were males. Most had warm antibodies (80.0%) and some secondary to viral (14.3%) or autoimmune disorders (31.4%). Seven (20.0%) patients presented with Evans syndrome, 3 of whom also had common variable immunodeficiency. The median hemoglobin at diagnosis was 6.1 g/dL and 62.8% patients required red cell transfusions. The severity of anemia was worse among children below 10 years (median 5.5 vs. 7.0 g/dL, P=0.01). Steroid was the initial treatment for 88.5% patients, with overall response rate of 82.7% (68.5% complete, 14.2% partial) and median response duration of 10.7 months (range, 0.2 to 129.7+ mo). After median follow-up of 26.6 months, 8 (22.8%) patients relapsed. Salvage treatments included splenectomy, intravenous immunoglobulin, rituximab, and mycophenolate mofetil. Infectious complications occurred in 9 (25.7%) patients and 1 patient died of cytomegalovirus infection. Four patients had cold agglutinin disease and 3 (75.0%) responded to steroids. Autoimmune hemolytic anemia is a rare disorder in pediatric population and most respond well to steroids regardless of the type of antibody. Infectious complications are common and screening for immunodeficiency is recommended among those with Evans syndrome.