Antibody response to oxidized epitopes and oral bacteria in atherosclerosis

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Leena Palotie auditorium 101A (Aapistie 5A)

Topic of the dissertation

Antibody response to oxidized epitopes and oral bacteria in atherosclerosis

Doctoral candidate

M.S., M.D Mikael Kyrklund

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Biomedicine

Subject of study

Medicine

Opponent

Professor Seppo Meri, University of Helsinki

Custos

Professor Sohvi Hörkkö, University of Oulu

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The association between oral health and atherosclerotic disease

Atherosclerosis is regarded as a chronic inflammatory disease where infections with various bacteria or viruses contribute to the disease development. LDL (low-density lipoprotein) oxidization is the first key step in the progression of atherosclerosis. Lipid oxidation produces adducts, such as malondialdehyde acetaldehyde (MAA), which are highly immunogenic and promote atherosclerosis.

This thesis investigates the cross-reactivity of antibodies between the epitopes on oxidized LDL molecules and antigen structures on oral bacteria. In the first study, immunization of mice with Porphyromonas gingivalis elevated the IgM antibody levels to MAA-LDL, implying a possibility of molecular mimicry between the epitopes on P. gingivalis and MAA adducts. Mice immunized with P. gingivalis also had less atherosclerosis compared to the control group, suggesting a protective role of IgM antibodies to MAA adducts.

In the second study, mouse natural monoclonal IgG antibodies specific to MAA were cloned and their binding characteristics to oral pathogens were analyzed. IgG antibodies specific to MAA cross-reacted with P. gingivalis, recognizing important virulence factors. The results indicate that natural IgG antibodies could have an essential role in the innate immune defense.

The third study investigated the antibody response in heat shock protein 60 (HSP60) immunized mice. HSP60 from Aggregatibacter actinomycetemcomitans (Aa-HSP60) induced significant IgM and IgG responses towards MAA-LDL in mice. Further studies revealed that natural IgM antibodies originating from human developing fetuses’ umbilical cord blood recognized epitopes of MAA and Aa-HSP60. The data provided evidence of molecular mimicry between MAA epitope and HSP60 protein.

The molecular mimicry of oral pathogens epitopes and oxidized LDL molecules is one possible mechanism linking infections and atherosclerosis. This thesis provides novel information on antibodies’ cross-reaction that could further modulate the development of chronic inflammatory diseases.
Last updated: 3.2.2022