The activity of NAD- and NAD(P)-dependent dehydrogenases in lymphocytes of peripheral blood in Graves’ disease

BACKGROUND: The regulatory effect of thyroid hormones on the metabolism of the immune system cells (activation of oxidative processes, separation of oxidative phosphorylation and increased protein synthesis) depends on their number. Changes in the activity of intracellular enzymes in Graves’ disease (GD) can determine the mechanisms of maintaining autoimmune inflammation in relapse of the disease. The exact role of NAD(P)-dependent dehydrogenases in the development and maintenance of immune response in GD is still poorly investigated.

AIMS: To study the activity of NAD(P)-dependent dehydrogenases in lymphocytes of peripheral blood in patients with manifestation and relapse of GD to clarify the mechanisms of development and progression of the autoimmune process.

METHODS: A single-center, cohort, prospective, continuous, observational, open-label, controlled trial was conducted to evaluate the lymphocytes NAD(P)-dependent activity in 151 women with GD and hyperthyroidism, mean age 40.7±13.2, 52 (37.14%), who were on follow-up at the endocrinology center of Krasnoyarsk Regional clinical hospital from 2016 to 2019. The NAD(P)-dependent dehydrogenases activity measured using biochemiluminescence method.

RESULTS: In patients with newly diagnosed of GD, relative to the control values and levels detected in relapse group we observe the increase of G6PDH and decrease of NADH-LDH. In GD relapse group compare to the control range in blood lymphocytes decreases the activity of LDH and NAD(P)-ICDH. In patients with newly diagnosed GD, two positive сorrelation were found: between fT3 level and MDG activity (r=0.90, p=0.037), and between fT4 level and NAD(P)-ICDH activity (r=0.82, p=0.007). In patients with relapse of GD positive relationships between the concentration of TSH and the activity of LDH (r=0.73, p=0.039), and MDH (r=0.93, p=0.002), as well as in a pair of fT4 and NADGDH (r=0.70, p=0.036) were revealed.

CONCLUSION: The established differences in the activity of NAD(P)-dependent dehydrogenases in peripheral blood lymphocytes in patients with manifestation and relapse of GD can reflect in the first case the response of immune cells to a functional-regulatory signal with the development of hyperthyroidism, and in the second case, adaptive changes with the progression of autoimmune process.

Graves’ disease, immunopathogenesis, thyrostatic therapy, lymphocytes, intracellular metabolism, NAD - and NAD(P)-dependent dehydrogenases

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