Involvement of Latent/Persistent Parvovirus B19, HHV-6 and HHV-7 Infections in Ethiopathogenesis of Rheumatoid Arthritis and Relationship with Clinical and Radiological Findings. Doctoral Thesis

Promocijas darbs izstrādāts Rīgas Austrumu klīniskās universitātes slimnīcas klīnikā “Linezers” un klīnikā “Gaiļezers”, Traumatoloģijas un ortopēdijas slimnīcā, RSU A. Kirhenšteina Mikrobioloģijas un virusoloģijas institūtā un RSU Anatomijas un antropoloģijas institūtā. Aizstāvēšana: 2018. gada 18. janvārī plkst. 15.00 Rīgas Stradiņa universitātes Medicīnas promocijas padomes atklātā sēdē Rīgā, Dzirciema ielā 16, Hipokrāta auditorijā.Rheumatoid arthritis (RA) is a chronic, progressive joint inflammation that causes destructive joint changes. RA reduces the quality of life and survival and creates a socio-economic burden. Despite long-term studies, the exact cause of the disease is unclear. As a contributing external factors include smoking, high caffeine consumption, frostbite and psycho-emotional or physical stress, as well as a variety of infectious agents - both bacteria and viruses. The most commonly studied viral agents are parvovirus B19 (B19V), rubella virus, human herpesviruses and others. The aim of the study was to compare RA patients with OA patients and healthy control subjects, and confirm or deny B19V, HHV-6 and -7 infections role in etiopathogenesis of RA, as well as to evaluate B19V, HHV-6 and -7 infectious activity of the different stages of the impact on RA clinical and laboratory activity, aggression and radiological stage. Persistent B19V, HHV-6 and -7 infection and the activity phases estimated using the nested PCR, and B19-specific antibodies were detected using recomWell and recomLine tests. Plasma cytokine expression estimated by ELISA. The results showed that RA patients have often B19V infection, the disease may begin not only temporarily after B19V infection but also as a consequence of prolonged B19V expression in the host tissues and chronic immune activation. Both active and acute B19V infection, by several clinical and laboratory parameters, affects both the disease activity and its aggression. RA patients’ T-cell proliferative response to B19V antigens is more common and more rapid compared to normal healthy subjects, indicating a persistent B19V infection in the presence of RA patients. Treatment with methotrexate (MTX) suppresses the T lymphocyte proliferative response to B19V antigens. The combination of sSMARM therapy also reduces the T lymphocyte proliferative response to B19V antigens. The persistence of different stages of B19V infection, as well as the duration of the infection before the patient is included in the study, have a slight effect on the clinical and laboratory progression of OA. The active HHV-6 and HHV-7 infection has a greater effect on RA activity, less aggression. Concomitant reactivation of HHV-6 and HHV-7 may result in a more aggressive RA course. The disease is also affected by HHV-6 and HHV-7 infection in the latent stage. The results of the study can be helpful in understanding RA’s development and in choosing a therapeutic strategy.Promocijas darbs veikts ar Valsts pētījumu programmu “Jaunu profilakses, ārstniecības, diagnostikas līdzekļu un metožu, biomedicīnas tehnoloģiju izstrāde sabiedrības veselības uzlabošanai (PUBLIC HEALTH)”, 2010.–2013. gads, un “Biomedicīna sabiedrības veselībai (BIOMEDICINE)”, 2014.–2017. gads, atbalstu