Chlamydien und Gonokokken – mehr als Erreger der weltweit häufigsten sexuell-übertragbaren Infektionen? Bindung antibakterieller Antikörper an Proteine des humanen fetalen Gehirns – Molekulare Identifizierung und funktionelle Charakterisierung zellulärer Interaktionspartner
Chlamydia and gonococci - more than the pathogens of the most common sexually transmitted infections worldwide? Binding of Antibacterial Antibodies to Proteins of the Human Fetal Brain - Molecular Identification and Functional Characterization of Cellular Interaction Partners
von Abdullah Ahmed Almamy
Datum der mündl. Prüfung:2020-10-08
Erschienen:2020-09-22
Betreuer:Prof. Dr. Bernhard Reuss
Gutachter:Prof. Dr. Bernhard Reuss
Gutachter:PD Dr. Fred Lühder
Gutachter:Prof. Dr. Thomas Meyer
Dateien
Name:Dissertation_Almamy_eDiss2.pdf
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Format:PDF
Zusammenfassung
Englisch
Neisseria gonorrhoeae and Chlamydia trachomatis are the bacterial pathogens of the most common sexually transmitted infections worldwide. The clinical presentation of the infections is variable. A large number of patients are asymptomatic. This is one of the main reasons for the high incidence rate. Both bacteria are able to trigger a strong immune response, which can also damage the body's own tissue. The damage to the body's own tissue by the own immune system is called an autoimmune reaction. Various hypotheses exist for the development of such reactions. In addition to the proven genetic predisposition to autoimmune diseases, there is now a scientific consensus that environmental factors play an essential role in triggering autoimmune diseases. These environmental factors include bacterial infections. Through the mechanism of molecular mimicry antibacterial antibodies can bind to human endogenous proteins due to structural similarity to bacterial proteins. This triggers an autoimmune reaction. Pregnant women in the first trimester of pregnancy represent a special group of patients. Epidemiological studies show an increased risk of developing a psychiatric illness in the offspring of the affected mothers. Our hypothesis suggest that an autoimmune reaction, mediated by autoantibodies that are able to cross the placenta, can disrupt the neuronal development of the embryo. The Task of the present work is to identify possible human interaction partners of the antibacterial antibodies. For this purpose, the cross-reactivity of antibacterial antisera against the bacteria Neisseria gonorrhoeae and Chlamydia trachomatis with proteins of a multiprotein array of prenatal human brains from the first trimester of pregnancy was investigated. As these studies show, antisera against Neisseria gonorrhoeae interact with proteins such as Snap23, Tspan7 and Selenoprotein H, proteins that are known to play a role in the development of schizophrenic psychoses. In contrast, antisera against Chlamydia trachomatis and other types of chlamydia showed fewer interaction partners, of which the ribosomal protein Rps27a. This protein could play a possible role in the development of neuropsychiatric disorders of systemic lupus erythematosus. Investigations of the effects on the main functions of the interaction partners Snap23 and Rps27a in cell culture models of the central nervous system (SH-SY5Y) and the choroid plexus (HIBCPP) showed an impairment of the functions of both proteins. Due to the disruption of the function of Snap23 as a regulator for membrane translocation in neuronal cells and the disruption of the function of Rps27a in protein synthesis in cells of the choroid plexus and thus the impairment of the supply and detoxification organ of the central nervous system, it can be assumed that this could result in disrupting the neural development. The results of the present work show previously unknown interactions and thus provide an experimental basis for further research regarding a possible autoimmune-inflammatory component of psychiatric diseases. However, the effects determined by in-vitro models still have to be evaluated for their clinical relevance in further in-vivo studies.
Keywords: autoimmunity; STD; schizophrenia; Lupus; molecular mimicry; choroid plexus; NPSLE; chlamydia; gonococci
Schlagwörter: Autoimmunität; STI; Schizophrenie; Lupus; NPSLE; Molekulare Mimikry; chlamydien; gonokokken