Lic.-avh. (sammanfattning) Stockholm : Karolinska institutet, 2009.

Thesis (M.S.)--Ohio University, March, 2010. / Title from PDF t.p. Release of full electronic text on OhioLINK has been delayed until October 1, 2010. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 182-210). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 182-210). Also available on the Internet.

Thesis (Ph.D. in Immunology) -- University of Colorado at Denver and Health Sciences Center, 2005. / Typescript. Includes bibliographical references (leaves 91-100). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

- / -

Introduction: Periodontal disease is one of the most common inflammatory diseases in the world. A possible autoimmune aspect behind the local tissue destruction in periodontal disease, as a result of the invasion of oral pathogens over time has been reported in previous studies, but the correlation is yet unclear. Purpose: The aim of this literature review was to shed light on the topic if autoantibodies and autoimmune reactions are associated with gingivitis, periodontitis or peri-implantitis and the progression of these inflammatory diseases. Material and methods: A search in the Pubmed database was done resulting in 138 hits. To follow a systematic approach for selecting the studies to include, we used predefined inclusion and exclusion criteria Results: 26 articles studying a broad variety of different autoantibodies was included for this literature review. A vast majority of the included studies were of case-control design and, because of the broad variety and different variables and data, we decided that a meta-analysis could not be performed. Conclusion: Many studies where results could be compared due to similar comparisons, regarding the incidence of periodontal disease and the prevalence of certain autoantibodies, showed opposite results which makes it hard to reach a conclusion. The main part of the included studies were of small size and therefore more comparable studies are needed to clarify the possible association between periodontal disease and an autoimmune reaction mediated by autoantibodies.

Antiphospolipidsyndrome (APS) is one of the most common autoimmune diseases characterized bythrombosis, fetal loss and presence of antiphospholipid antibodies. In APS research the antibodies of biggestinterest are anti-β2-glycoprotein I antibodies (Aβ2GPIA). β2-glycoprotein I (β2GPI)is a plasma protein which becomes activated and obtains a open structure incontact with negative charged surface molecules such as phospholipids. Inactiveβ2GPI has a closed, circular shape which can’t bind autoantibodies. Thereis no golden standard for APS diagnosing and the methods used often giveinconsistent results. The purpose of this examination project work was toconvert β2GPI into the open and closed forms, respectively, by dialyzing againsthigh ionic strength, low and high pH and determine if there is any differencein binding capacity between the two forms and Aβ2GPIAon a microtiter plate.                                                The binding capacity was tested inan ELISA (enzyme-linkedimmunosorbent assay) using purified IgG from patient sera and thedifferent conformational forms of β2GPI. An ELISA for measuring of Aβ2GPIAon several patient samples was also performed.               No difference in binding capacitycould be detected which might be explained by that the conversion of β2GPI was unsuccessful.Perhaps no difference can be measured between the structures because the closedform is expected to open on microtiter plates. An unexpected result was thepresence of immune complexes of β2GPI-Aβ2GPIA found in the serum of one of the patients. In theory an ELISA based on theopen form of β2GPI would provide more reliable diagnoses and furtherresearch is needed in this area.

Introdução: O infliximabe é um anticorpo monoclonal quimérico que inibe o fator de necrose tumoral, sendo usado em doenças autoimunes e/ou inflamatórias, tais como a artrite reumatóide (AR), a espondilite anquilosante (EA), a psoríase e a artrite psoriásica (AP) e as doenças inflamatórias intestinais (DII). Objetivos: Avaliar se o infliximabe induz à formação de autoanticorpos e verificar a ocorrência de eventos adversos, sobretudo o lúpus induzido por este medicamento. Metodologia: Trata-se de um estudo aberto, prospectivo, de fase IV, onde dosamos os autoanticorpos antes e depois do tratamento (das doenças citadas anteriormente), o qual teve duração mínima de 6 meses (5 infusões). Resultados: No total, 286 pacientes foram avaliados para o fator anti-nuclear (FAN) por imunofluorescência indireta em células Hep2, sendo significativo o aumento de número de indivíduos (p = 0,0001), antes e depois da medicação. Além do FAN, foram dosados, em 146 pacientes, 17 outros autoanticorpos pelo método multiplex, sendo que o anti-DNA de dupla hélice (anti-dsDNA) e o anticardiolipina IgM (aCL IgM) tiveram um aumento significativo (p = 0,003 e 0,0024, respectivamente). Pacientes com AR tiveram uma variação significativa nos títulos do anticorpo anti-proteína citrulinada (ACPA) (antes e depois do tratamento) (p = 0,012). De todos os pacientes avaliados (n = 286), somente 1 (0,35%) apresentou sinais clínicos e laboratoriais de lúpus induzido pelo infliximabe. Conclusão: O estudo demonstrou que o infliximabe interferiu na formação de autoanticorpos (FAN, anti-dsDNA, aCL IgM e ACPA), sendo rara a indução de lúpus pelo medicamento. / Background: Infliximab is a chimeric monoclonal antibody that inhibits tumor necrosis factor, and is thus used in the treatment of autoimmune and/or inflammatory diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis and psoriatic arthritis (PA), and inflammatory bowel diseases (IBD). Objective: To determine whether infliximab induces the formation of autoantibodies and assess the occurrence of adverse effects, mainly drug-induced lupus. Method: The study consisted of a phase IV, prospective, open-label trial, in which autoantibody levels were determined before and after treatment (of the above mentioned diseases) with a minimum duration of 6 months (5 infusions). Results: A total of 286 patients were assessed for the presence of antinuclear antibodies (ANA) by means of indirect immunofluorescence on human epithelial (HEp-2) cells, with a significant increase in the number of individuals observed after treatment (p = 0.0001). In addition to ANA, 17 other autoantibodies were assessed in 146 patients using multiplex technology, and a significant increase was observed in anti-double stranded DNA (anti-dsDNA) and anticardiolipin IgM (aCL IgM) antibody titers (p = 0.003 and 0.0024, respectively). Patients with RA showed significant variations in anti-citrullinated protein antibody (ACPA) titers (before and after treatment) (p = 0.012). Among the 286 patients assessed, only 1 (0.35%) presented clinical and laboratory signs of infliximab-induced lupus. Conclusion: The present study showed that infliximab did affect the formation of autoantibodies (ANA, anti-dsDNA, aCL IgM and ACPA), with a rare occurrence of drug-induced lupus.

Introduction: Idiopathic inflammatory myopathies (myositis, IIM) are heterogeneous group of rare autoimmune systemic diseases, characterized particularly by proximal skeletal muscle weakness. Heretogeneity of myositis is based on different pathogenetic mechanisms which may be reflected by variable imunophenotypic response in individual subtypes. Objectives: The aim of this work was to explore the associations and influence of soluble factors of immune system in patient's sera on phenotypic characteristics and subtypes of IIM, to describe their expression in inflammed muscle tissue and study their eventual role in pathogenesis by analysis of effect on immune and muscle cells in vitro. Results: We have described prevalence and characteristics of joint involvement in myositis patients and its significant association with anti-Jo-1 autoantibody. Further we confirmed the relation of anti-HMGCR antibody to immune mediated necrotizing myopathy, its tight relation to statins and recent increase in incidence. We showed inverse association of IFNα serum levels with muscle activity detected on MRI. Clinical activity positively correlated with IFN type-I pathway activation in patients with dermatomyositis. We also show positive correlation of resistin levels and clinical activity and correlation of activity...