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

2020 ◽  
Vol 66 (2) ◽  
pp. 33-41
Author(s):  
Margarita A. Dudina ◽  
Andrey Savchenko ◽  
Sergey A. Dogadin ◽  
Ivan I. Gvozdev

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 40.713.2, 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.

2010 ◽  
Vol 31 (7) ◽  
pp. 1238-1241 ◽  
Author(s):  
P. Vodicka ◽  
Z. Polivkova ◽  
S. Sytarova ◽  
H. Demova ◽  
M. Kucerova ◽  
...  

2021 ◽  
Vol 67 (6) ◽  
pp. 39-49
Author(s):  
M. A. Dudina ◽  
S. A. Dogadin ◽  
A. A. Savchenko ◽  
V. D. Belenyuk

BACKGROUND: Effective control of autoimmune inflammation in Graves’ disease determines necessity to study the T helper (Th) and cytotoxic T-lymphocytes dysfunction, as well as the level of regulatory T-cells (Treg) activation in patients with Graves’ disease on thyrostatic medication, which will clarify the immunomodulatory effects of long-term thiamazole treatment serve as targets for more specific therapies.AIM: To study the phenotypic composition of T-lymphocytes in the peripheral blood of patients with Graves’ disease to assess the direction of immune response depending on thimazole-induced euthyroidism duration.MATERIALS AND METHODS: A single-center, cohort, continuous, open-label, controlled trial was conducted to assess the phenotypic composition of T-lymphocytes in peripheral blood in women with Graves’ disease on long-term thiamazole treatment. The phenotypic composition of T-lymphocytes was determined by flow cytometry using direct immunofluorescence with conjugated FITC monoclonal antibodies depending on the duration of thimazole-induced euthyroidism of long-term thiamazole treatment.RESULTS: The study included 135 women with Graves’ disease, mean age 43.09±12.81 years, 120 (88.91%) with a relapse of the disease and 15 (11.09%) with newly diagnosed hyperthyroidism. An increase of activated CD3+CD4+CD25+ was found in patients with Graves’ disease with a duration of thimazole-induced euthyroidism 5–8 months and 9–12 months, respectively, Me=0.94 (0.48–1.45), p=0.020) and Me=0.95 (0.41–1.80), p=0.025), in control group — Me=0.12 (0.03–0.68). Compared to the control an increase of CD4+CD25+CD127Low (Treg) was found in patients with a duration of thimazole-induced euthyroidism 5–8 and 9–12 months. The content of Treg in peripheral blood in Graves’ disease patients with a duration of thimazole-induced euthyroidism more than 12 months decreases, but remains elevated relative to the control.CONCLUSION: In patients with Graves’ disease with a duration of thimazole-induced euthyroidism 5–8 months and 9–12 months the level of Treg has been increased. The increase of activated Th (CD3+CD4+CD25+) persists independently of thimazole-induced euthyroidism. In patients with Graves’ disease with a duration of thimazole-induced euthyroidism for more than 12 months, there is a compensatory increase in regulatory T-lymphocyte, and the total number of T-helpers is restored to the control.


1989 ◽  
Vol 69 (3) ◽  
pp. 648-653 ◽  
Author(s):  
VIOLAINE GUERIN ◽  
MARIE-CHRISTINE BENE ◽  
CORINNE AMIEL ◽  
PIERRE HARTEMANN ◽  
JACQUES LECLERE ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1896-1896
Author(s):  
Duck Cho ◽  
Mark H. Yazer ◽  
Myung-Geun Shin ◽  
Jong-Hee Shin ◽  
Soon-Pal Suh ◽  
...  

Abstract A chimera is an organism whose DNA is derived from multiple zygotes whereas a mosaic individual’s DNA is entirely derived from a single zygote. We report a case of a chimera who also had cytogenetic features of mosaicism. A 39-year old father of one child, healthy, morphologically normal Korean male with apparent B3 blood group was identified at the time of blood donation. On forward typing 50% of his RBCs were strongly agglutinated by monoclonal anti-B in the manual tube method. The remaining RBCs were type O. Reverse typing revealed a strong anti-A. Complete ABO exon and flanking intronic region sequencing unexpectedly revealed an O01/O02 genotype. He had never been transfused nor received a BMT, and denied having a twin. Chimerism or mosaicism was suspected so additional specimens were collected from the propositus and his parents. Extended RBC phenotyping of the propositus by the gel card technique using monoclonal reagents revealed mixed field agglutination in the M, Kpb, Lub and Jka antigens. B allele haplotype-specific PCR, and exon 6 and 7 cloning and sequencing performed on genomic DNA from the propositus revealed a third ABO allele, B101. Sequencing of exons 6 and 7 and flanking intronic regions of his parents’ ABO alleles revealed a B101 allele in both parents along with an O01 allele (maternal) and an O02 allele (paternal). A total of 9 STR loci were analyzed on DNA extracted from blood, buccal swabs and hair from the propositus and on DNA isolated from peripheral blood lymphocytes from both his parents. Four loci demonstrated a pattern consistent with a double paternal DNA contribution, thus confirming the presence of chimerism (Table 1). Sequence-based typing of HLA class I and II loci was performed on DNA from peripheral blood lymphocytes from these 3 family members but revealed only a single allelic contribution from both parents in the propositus. The propositus’ karyotype revealed a mosaic pattern with 32/50 metaphases demonstrating 46, XY and 18/50 metaphases demonstrating 47, XYY. Overall, an extra paternal set of DNA markers was demonstrable by STR analysis in tissues arising from different germ layers. The propositus is thus a dispermic chimera most likely resulting from parthenogenetic division of the ovum and its subsequent fertilization by two spermatozoa: one with a 23, Y DNA complement and the second with a different 24, YY complement. This would explain the apparent single maternal DNA contribution. Alternatively a non-dysjunction event producing the mosaic 47, XYY karyotype could have occurred after fertilization. Given the mixed field blood group his ABO genotype is most likely B101/O01 and O01/O02. Consistent with other cases of mosaic 47, XYY syndrome our propositus is healthy, morphologically normal and fertile. This is the first case of a dispermic chimera with mosaic 47, XYY syndrome detected at the time of blood donation. STR results demonstrating a double paternal DNA contribution in disparate tissues DNA polymorphism Father Mother Propositus (blood) Propositus (buccal swab) Propositus (hair) D3S1358 15,16 16,17 15,16,17 15,16,17 15,16,17 D5S818 10,12 9,13 10,12,13 10,12,13 10,12,13 D13S317 12,14 8,9 9,12,14 9,12,14 9,12,14 D18S51 16,19 14,15 15,16,19 15,16,19 15,16,19


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