IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide with a very severe prognosis, causing kidney failure in up to 50 % of patients in a period of 30 years. For the diagnosis of IgAN it is necessary to perform a renal biopsy, this is an invasive examination that carries number of risks for the patients (the most common is bleeding and others). The aim of our work was to identify markers that could facilitate diagnosis and might help in determining the disease activity with an estimate of prognosis and consequently optimal use of effective therapy. In the pilot project on 19 patients with different types of glomerulonephritides (IgAN, diabetic nephropathy, membranous glomerulonephritis, lupus nephritis, ANCA associated vasculitis) and 19 healthy subjects we demonstrated a panel of 7 biomarkers (8-hydroxyguanosine, dodecanal, leukotriene C4, alpha1-antitrypsin, heparan sulfate , IgA-uromodulin, Gd-IgA1) that were able to completely differentiate patients with IgAN from other types of glomerulonephritides or healthy controls. In a group of 93 Czech patients with IgAN we confirmed the influence of clinical factors (PU, HT, eGFR) on the progression of renal function. Using LDA and logistic regression modelling we found that serum Gd-IgA1 (native without pre-treatment with...

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

We have developed a solid-phase radioimmunoassay capable of detecting nanogram quantities of human IgA rheumatoid factor (RF) in biological fluids. Human IgM RF, IgG RF, IgG, IgA, IgM and whole serum did not significantly interfere with the IgA RF assay. Patients with sero-positive rheumatoid arthritis (RA) had significantly higher concentrations of IgA RF than sero-negative RA patients or healthy adult controls. Concentrations of IgA RF in paired sera and synovial fluids from sero-positive RA patients were comparable. Levels of IgA RF demonstrated a moderately good correlation with levels of IgM RF in sero-positive RA sera (r = 0.673). However, the ratio of IgA RF concentration to IgM RF concentration in sero-positive RA sera varied widely.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

No description available.

Li Kam-tao, Philip. / "January 2003." / Thesis (M.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 252-281). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Les entérobactéries Salmonella sont divisées en plusieurs sérovars dont les quatre principaux Typhimurium, Enteritidis, Typhi et Paratyphi sont responsables soit de gastroentérites soit de fièvres typhoïdes, à raison de plus de 90 millions de cas et 400 000 décès par an. L’apparition de souches multi-résistantes nécessite la mise en place d’une vaccination prophylactique muqueuse. L’environnement intestinal est caractérisé par une balance entre tolérance immunitaire et réaction inflammatoire régulée par les immunoglobulines (Ig) A sécrétoires. Les IgA des sécrétions muqueuses sont dimériques, les IgA sériques sont monomérique et deux isotypes ont été décrits chez l’Homme: IgA1 et IgA2. Nous avons tout d’abord exploré les fonctions des différents isotypes et isoformes des IgA humaines. Nous avons pu noter un rôle anti-inflammatoire des IgA1 à l’inverse d’un rôle pro-inflammatoire des IgA2 et nous avons souligné un processus de régulation de l’expression des récepteurs aux IgA par les IgA elles-mêmes ainsi qu’un axe IgA/lymphocytes T CD8 cytotoxiques. Nous avons ensuite mis en place un vaccin multivalent composé des antigènes SseB et OmpC de Salmonella liés à des Ig sécrétoires. Cette étude a mis en évidence une solide réponse immunitaire humorale et cellulaire spécifique aux antigènes couplés à des IgA ou IgM après vaccination intra-nasale au niveau systémique et muqueux. Par ailleurs, de plus fortes réponses humorales et systémiques spécifiques ont été observées en couplant à la fois OmpC et SseB sur l’IgA. Ce travail de thèse ouvre de nouvelles perspectives pour la mise en place de vaccins muqueux multivalents et pourrait apporter des réponses quant au rôle des IgA. / The enterobacteria Salmonella species are divided into several serovars such as Typhimurium, Enteritidis, Typhi and Paratyphi which are the major causative agents of either gastroenteritis or typhoid fever. They are responsible for more than 90 million cases and 400 000 deaths each year. The increase in multi-drug resistant strains requires the implementation of prophylactic mucosal vaccines. Besides, the intestinal environment is characterized by a balance between immune tolerance and inflammatory response tightly regulated by secretory immunoglobulins (Ig) A. Mucosal IgA are mainly dimeric, serum IgA monomeric and two IgA isotypes have been described in humans: IgA1 and IgA2. We firstly explored the functions of the different isotypes and isoforms of human IgA. We pointed out a pro-inflammatory role of IgA2 whereas IgA1 rather oriented the immunity towards an anti-inflammatory response. We have also highlighted both the regulation of IgA receptors expression by IgA and an IgA/CD8 cytotoxic T cells axis. We also designed a multivalent vaccine against Salmonella by coupling two antigens – SseB and OmpC – to secretory Ig. We pointed out solid specific humoral and cellular responses against both these antigens coupled to either IgA or IgM after intra-nasal immunization in mucosal but also systemic compartments. We have also demonstrated the possibility to preserve and increase the antigen immunogenicity with a multivalent vaccine. This thesis thus paves the way for new secretory Ig-vectorized mucosal vaccines. In addition, the immune response could be modulated through the chosen isotype or isoform and the differences in immune activation generated by structural changes in IgA could shed some light on their role in mucosal homeostasis.

No description available.

published_or_final_version / Medicine / Master / Master of Philosophy

Chui Shiu Hon. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 144-183. / ACKNOWLEDGEMENTS / SUMMARY / LIST OF ABBREVIATIONS / Chapter CHAPTER 1. --- INTRODUCTION --- p.1 / Chapter 1.1 --- IgA Nephropathy --- p.1 / Chapter 1.1.1 --- History & Epidemiology --- p.1 / Chapter 1.1.2 --- Clinical Pathological Features --- p.2 / Chapter 1.1.3 --- Laboratory Findings --- p.3 / Chapter 1.1.4 --- Immunopathogenesis --- p.5 / Chapter 1.2 --- The Role of IgA in the Pathogenesis of IgA Nephropathy --- p.10 / Chapter 1.2.1 --- Structure of IgA Molecule --- p.10 / Chapter 1.2.2 --- IgA Biosynthesis and Immune Regulation --- p.23 / Chapter 1.2.3 --- Biological Role of IgA --- p.26 / Chapter 1.2.4 --- Circulating Immune Complexes in IgA Nephropathy --- p.27 / Chapter 1.2.5 --- IgA Subclasses in IgA Nephropathy --- p.32 / Chapter 1.2.6 --- Light Chain Composition of IgA in IgA Nephropathy --- p.33 / Chapter 1.3 --- Aim of the Present Study --- p.36 / Chapter 1.4 --- Design of Experiments --- p.37 / Chapter CHAPTER 2. --- MATERIALS & METHODS --- p.42 / Chapter 2.1 --- Materials --- p.42 / Chapter 2.1.1 --- Patients --- p.42 / Chapter 2.1.2 --- Controls --- p.43 / Chapter 2.1.3 --- Additional Specimens --- p.43 / Chapter 2.1.4 --- Serum Samples --- p.44 / Chapter 2.1.5 --- Chemicals --- p.44 / Chapter 2.1.6 --- Immunoglobulins --- p.46 / Chapter 2.1.7 --- Antisera --- p.47 / Chapter 2.1.8 --- Solutions and Buffers --- p.48 / Chapter 2.1.9 --- Apparatus and Equipment --- p.51 / Chapter 2.2 --- Methods --- p.53 / Chapter 2.2.1 --- Serum Protein Electrophoresis --- p.53 / Chapter 2.2.2 --- Immunochemical Techniques --- p.54 / Chapter 2.2.3 --- Fast Protein Liquid Chromatography (FPLC) for Isolation of Serum IgA --- p.64 / Chapter CHAPTER 3. --- SERUM PROTEIN ELECTROPHORESIS AND IMMUNOGLOBULIN CONCENTRATIONS --- p.67 / Chapter 3.1 --- Serum Protein Electrophoresis --- p.67 / Chapter 3.2 --- Serum Immunoglobulin Concentration --- p.67 / Chapter 3.3 --- Discussion --- p.70 / Chapter CHAPTER 4. --- LIGHT CHAIN RATIOS OF INDIVIDUAL IMMUNOGLOBULINS --- p.72 / Chapter 4.1 --- Enzyme-Linked Immunosorbent Assay for Light Chain Concentrations --- p.72 / Chapter 4.2 --- Light Chain Ratios of Individual Serum Immunoglobulins in Normal Subjects and in Disease --- p.75 / Chapter 4.3 --- Discussion --- p.77 / Chapter CHAPTER 5. --- IN VITRO SYNTHESIS OF IgA WITH LAMBDA LIGHT CHAIN IN IgA NEPHROPATHY --- p.83 / Chapter 5.1 --- Lymphocyte Culture and In Vitro Immunoglobulin Production --- p.83 / Chapter 5.2 --- In Vitro Immunoglobulin Production and Predominant Synthesis of IgA with λ Light Chain in IgA Nephropathy --- p.83 / Chapter 5.3 --- Dicussion --- p.87 / Chapter CHAPTER 6. --- PURIFICATION OF SERUM IgA BY AFFINITY CHROMATOGRAPHY --- p.90 / Chapter 6.1 --- Fast Protein Liquid Chromatography --- p.90 / Chapter 6.2 --- Recovery of Isolated IgA --- p.92 / Chapter 6.3 --- Purity of Isolated IgA --- p.92 / Chapter 6.4 --- κ/λ Ratio of IgA Before and After FPLC --- p.96 / Chapter 6.5 --- Subclass of IgA Before and After FPLC --- p.97 / Chapter 6.6 --- Discussion --- p.100 / Chapter CHAPTER 7. --- "ANALYSIS OF CHARGE DISTRIBUTION OF IgA, IgA(κ) AND IgA(λ)" --- p.102 / Chapter 7.1 --- "Iso-Electric Focusing, Immunoblotting, and Densitometry of Purified IgA for Total IgA, IgA(κ) and IgA (λ)" --- p.102 / Chapter 7.2 --- "Charge Distribution of Plasma Total IgA, IgA(κ) and IgA(λ)" --- p.103 / Chapter 7.2.1 --- A/C Ratio of Total IgA --- p.103 / Chapter 7.2.2 --- A/C Ratio of IgA(κ) --- p.113 / Chapter 7.2.3 --- A/C Ratio of IgA(λ) --- p.113 / Chapter 7.3 --- Discussion --- p.129 / Chapter CHAPTER 8. --- GENERAL DISCUSSION --- p.134 / REFERENCES --- p.140 / APPENDICES