Immune system parameters in chronic opisthorchiasis patients related to genes polymorphisms associated with developing ischemic heart disease

To identify the features of immune system functioning in patients with chronic opisthorchiasis coupled to mutant gene loci associated with arterial hypertension predisposition, comprehensive studies on innate and adaptive immunity were conducted. The state of neutrophil engulfment and bactericidal activity was assessed. The phenotype of lymphocytes was determined by flow cytometry. The humoral arm of the immune system was assessed by quantitating total immunoglobulins of classes M, G, A and E. Gene polymorphisms were detected by pyrosequencing. The predisposition to arterial hypertension development was assessed by assessing polymorphisms in the gene loci: ARDB2 rs1042713; AGT rs4762; AGT rs699; AGTR1 rs5186; NOS3 rs1799983. In patients with chronic opisthorchiasis with and without polymorphisms AGT rs4762 and AGTR1 rs5186, had no difference in immune response. Patients with vs. without ARDB2 rs1042713 had suppressed humoral (reduced total IgE) along with activated innate immune response in chronic opisthorchiasis (increased absolute count of leukocytes and monocytes). In the group with the rare AGT rs699 vs. common allele there was a decrease in the percentage of lymphocytes, a lower total IgM level and increased percentage of B lymphocytes. Immune indicators in patients with chronic opisthorchiasis with vs. without rs1799983 mutation in the NOS3 gene had higher neutrophil bactericidal potential (stimulated nitrosine tetrazolium test (NST test)) along with percentage of T-helper cells (CD4+).

Immunological Parameters in Patients With Chronic Opisthorchiasis Coupled to Mutant Genes Associated With Predisposition to Arterial Hypertension Development

Grigorieva,

Stepanova,

Stepanova T.F.

et al. 2024

IImmunological parameters in patients with chronic opisthorchiasis bearing gene mutations associated with osteoporosis-predisposition

Kurlaeva,

Stepanova,

Stepanova

et al. 2023

To identify the features of the immune system functioning in patients with chronic opisthorchiasis bearing mutations in loci associated with predisposition to developing osteoporosis, comprehensive studies of cellular and humoral arms were carried out. The state of the phagocytic system was assessed by assessing absorption, metabolic activity and reactive oxygen species formation to restore nitrosine tetrazolium (spontaneous and stimulated NST test). The phenotype of lymphocytes was determined by flow cytometry. The humoral immune arm was evaluated by the number of immunoglobulin classes M, G, A and E. Differences in the functional state of various arms of the immune system were revealed. In patients with chronic opisthorchiasis in the presence of rs1544410 polymorphism of the gene encoding the intracellular vitamin D receptor, the relative number of T-helper cells is significantly lower than in the group with the normal allele. In the presence of rs1800012 polymorphism of the gene encoding the 1-chain of type I collagen, the absolute lymphocyte count is significantly higher, spontaneous and stimulated NST test were lower, the number of DN-T lymphocytes is significantly lower (both in relative and absolute values). In the presence of the rs3736228 mutation of the gene encoding the transmembrane low-density lipoprotein receptor, the level of myeloperoxidase and the neutrophil stimulation index are lower, the absorption activity of neutrophils is higher. The presence of the rs2234693 mutation for estrogen receptor gene leads to significantly increased level of stimulated NST test and IgG concentration. Thus, patients with chronic opisthorchiasis bearing mutations in the COL1 A1, LRP5, ESR1(rs2234693) genes, have altered both nonspecific innate reactions and parameters of the adaptive immune arm; mutation of the VDR gene s9lely affects adaptive immunity. Analysis of the results suggests that the presence of mutations associated with the development of osteoporosis has a modulating effect on the immune response in chronic opisthorchiasis invasion. The identification of polymorphic genes associated with metabolic disorders of bone tissue and the study of the immunological profile in patients with chronic opisthorchiasis invasion will allow to implement an individual approach in the treatment of such patients.

Immune system parameters in patients with chronic opistorchiasis based on genetic polymorphism associated with carbohydrate and lipid metabolism disorders

Bakshtanovskaya,

Grigorieva,

Stepanova

et al. 2024

Self Cite

A study assessing differences in the immunopathogenesis of chronic opisthorchiasis with or without genetic polymorphisms in patients associated with predisposition to type II diabetes mellitus and lipid metabolism disorders was carried out. Venous blood samples from 89 patients were collected to analyze immunological parameters and genetic polymorphisms by using pyrosequencing. In the presence of mutations affecting regulation of carbohydrate metabolism, patients with opisthorchiasis had less pronouncedly increased phagocytic activity, a lower monocyte count, higher total T-lymphocyte count, lower T-cytotoxic cell and B-lymphocyte counts, lower IgA, IgG but higher IgM concentration. This indicates a moderately compromised nonspecific resistance, imbalanced effector T- and B-immunity, but in most cases (PPARG, TCF7L2 rs12255372, CDKAL1, CDKN2A/2B, SLC30A8) aggravated humoral immune reaction to invasion particularly revealed by lower B-lymphocyte count. The presence of polymorphisms that alter lipid metabolism regulation bidirectionally affects the parameters of immune response. An increased B-lymphocyte count and other indicators of humoral immune activation to invasion, which are detected in groups with mutations in the APOE (rs429358), PCSK9, ABCA1, APOC3 rs2854117 genes, can contribute to a more effective response to sustained antigenic stimulation. Changes in the T-lymphocytes subpopulations, characteristic of opisthorchiasis invasion, are aggravated in the presence of mutations in the PCSK9, ABCA1, and APOC3 rs2854117 genes. Mutations in the genes APOC3 rs5128, LPL rs268 activate patients’ nonspecific resistance, although this effect may also be associated with exhaustion of neutrophil bactericidal reserve. In general, minor alleles of the APOE (rs429358), APOC3 rs2854117, LPL rs268, LPL rs328, PON1 rs662 genes can be considered “protective” for the immunopathogenesis of chronic opisthorchiasis. Thus, patients with chronic opisthorchiasis with different genotypes predisposing to carbohydrate and lipid metabolism disorders had significant differences in immune system parameters, which can also affect the disease course. Mutations in different loci of the PCSK9, ABCA1, APOE, APOC3, and PON1 genes have opposite effects on the analyzed immune parameters. In the presence of mutations in other genes (PPARG, TCF7L2 rs12255372, CDKAL1, CDKN2A/2B, SLC30A8, LPL), opisthorchiasis invasion leads to more pronounced alterations in immune response; mutations in the lipoprotein lipase gene may have some “protective” immune-related effect in opisthorchiasis. The effect of all studied genetic polymorphisms associated with a predisposition to developing type II diabetes mellitus was predominantly negative.