Extracellular DNA level as an indicator of the activity of inflammatory reactions in patients with rheumatoid arthritis and asthma

Abstract

BACKGROUND: We performed a clinical and laboratory examination of patients with rheumatoid arthritis and bronchial asthma. Nosologies were selected to examine extracellular DNA changes in the blood during immunopathological processes based on generally accepted views on the role of helper balance in disease pathogenesis. The degree of disease activity in rheumatoid arthritis primarily depends on the severity of inflammatory changes in the joints; therefore, it is closely associated with a shift in the balance of helpers toward the Th1. According to today’s concepts, the pathogenesis of asthma is determined by the intensive production of specific antibodies, which are controlled by activated Th2 lymphocytes.

AIM: To study extracellular DNA changes in the blood of patients during immunopathological processes depending on the Th1/Th2 balance ratio and compare these data with the parameters of standard laboratory tests and indicators of neutrophil activities and their ability to netosis.

METHODS: Extracellular DNA concentration was determined using the Quant-ITTM PicoGreen fluorescent reagent for double-stranded DNA. Neutrophils isolated in a double-density gradient of ficoll–urografin were cultured with or without the addition of phorbol myristate acetate followed by Sytox Green.

RESULTS: The studied immunopathological conditions had significantly decreased extracellular DNA levels in the plasma of patients with asthma, which sharply contrasted with its increase in patients with arthritis. Laboratory parameters confirmed the presence of local inflammation in patients with asthma without obvious symptoms of a systemic inflammatory response, while in patients with arthritis, inflammatory changes in the joints were accompanied by an increased C-reactive protein level, indicating a systemic reaction of the body in response to inflammatory stimuli.

CONCLUSIONS: Thus, the state of the Th1/Th2 balance is assumed as one of the significant regulators that determined the extracellular DNA concentration in the blood. According to the proposed hypothesis, the shift in this ratio toward the predominance of Th1 cells should promote the development of inflammatory processes in the body and increase the amount of extracellular DNA, while a shift in the balance of helpers toward the dominance of Th2 lymphocytes should suppress these processes and consequently decrease the extracellular DNA in the blood.

Keywords

extracellular DNA / inflammation / rheumatoid arthritis / asthma / neutrophilic leukocytes / netosis / myelopyroxidase / proinflammatory cytokines

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Funding

«Изучение иммунопатогенеза фенотипов социально значимых заболеваний человека и полиморбидности как основа для разработки новых методов персонифицированной диагностики и лечения»“Study of the immunopathogenesis of phenotypes of socially significant human diseases and multimorbidity as the basis for the development of new methods of personalized diagnosis and treatment”(РК № 122012000366-9)

RIGHTS & PERMISSIONS

Volskiy N.N., Demchenko E.N., Goiman E.V., Kozlov V.A., Gavrilova E.D.