ABSTRACT
Aim: To ascertain whether killer cell immunoglobulin-like receptors (KIR) genes polymorphisms and HLA-I ligands are associated with COVID-19 in Saudi Arabia. Methods: Eighty-seven COVID-19 patients who tested positive for SARS-CoV-2 and one hundred and fourteen healthy controls were enrolled in this study for genotyping of the 16 KIR genes, HLA-C1 and -C2 allotypes and HLA-G 14-bp indels polymorphisms using the sequence specific primer polymerase chain reaction (SSP-PCR) method. KIR genotype frequency differences and combination KIR-HLA-C ligand were tested for significance. Results: Framework genes KIR2DL4, KIR3DL2, KIR3DL3, and KIR3DP2 were present in all individuals. The frequencies of KIR2DL2 and KIR2D4 were higher in COVID-19 positive patients than in healthy individuals. The frequencies of the combination KIR2DL2-HLA-C2 was also significantly higher in patients affected by COVID-19 compared with healthy controls. Conclusion: It was found that the inhibitory KIR2DL2 gene in isolation or combined with its HLA-C2 ligand could be associated with susceptibility to COVID-19 in the Saudi population.
ABSTRACT
The thymus is the main lymphoid organ that regulates the immune and endocrine systems by controlling thymic cell proliferation and differentiation. The gland is a primary lymphoid organ responsible for generating mature T cells into CD4+ or CD8+ single-positive (SP) T cells, contributing to cellular immunity. Regarding humoral immunity, the thymic plasma cells almost exclusively secrete IgG1 and IgG3, the two main complement-fixing effector IgG subclasses. Deformity in the thymus can lead to inflammatory diseases. Hassall's corpuscles' epithelial lining produces thymic stromal lymphopoietin, which induces differentiation of CDs thymocytes into regulatory T cells within the thymus medulla. Thymic B lymphocytes produce immunoglobulins and immunoregulating hormones, including thymosin. Modulation in T cell and naive T cells decrement due to thymus deformity induce alteration in the secretion of various inflammatory factors, resulting in multiple diseases. Influenza virus activates thymic CD4+ CD8+ thymocytes and a large amount of IFNγ. IFNs limit virus spread, enhance macrophages' phagocytosis, and promote the natural killer cell restriction activity against infected cells. Th2 lymphocytes-produced cytokine IL-4 can bind to antiviral INFγ, decreasing the cell susceptibility and downregulating viral receptors. COVID-19 epitopes (S, M, and N proteins) with ≥90% identity to the SARS-CoV sequence have been predicted. These epitopes trigger immunity for antibodies production. Boosting the immune system by improving thymus function can be a therapeutic strategy for preventing virus-related diseases. This review aims to summarize the endocrine-immunoregulatory functions of the thymus and the underlying mechanisms in the prevention of COVID-19.