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

Abstract

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.