Vitamin D deficiency leads to the abnormal activation of the complement system

Abstract

Vitamin D deficiency can damage the human immune system, and the complement system is a key component of the immune system. This study aimed to elucidate the mechanism by which vitamin D affects the immune system by analyzing the changes in the protein expression of the complement system under different vitamin D levels. We selected 40 participants and divided them into three groups according to their serum levels of 25-hydroxyvitamin D (25(OH)VD): group A, 25(OH)VD ≥ 40 ng/mL; group B, 30 ng/mL ≤ 25(OH)VD < 40 ng/mL; and group C, 25(OH)VD < 30 ng/mL. Serum samples were subjected to biochemical analysis, followed by proteomic analysis using high-throughput untargeted proteomic techniques. Vitamin D deficiency increased the levels of fasting blood sugar, fasting serum insulin, and homeostasis model assessment (HOMA) of insulin resistance and decreased the secretion of HOMA of β-cell function, which led to insulin resistance and glucose metabolism disorder. Moreover, vitamin D deficiency resulted in the abnormal expression of 56 differential proteins, among which the expression levels of complement factor B, complement component C9, inducible co-stimulator ligand, and peptidase inhibitor 16 significantly changed with the decrease in vitamin D content. Functional enrichment analysis of these differential proteins showed that they were mainly concentrated in functions and pathways related to insulin secretion and inflammation. In conclusion, vitamin D deficiency not only contributes to insulin resistance and glucose metabolism disorder but also causes abnormal protein expression, resulting in the abnormal activation of the complement system. This study provides a novel theoretical basis for further studies on the relationship between vitamin D and the immune system.

Reeling in complement in transplant‐associated thrombotic microangiopathy: You're going to need a bigger boat

“…Vitamin D deficiency can lead to abnormal complement activation and cause endothelial injury. 69,70 Vitamins D, A, C can also influence endothelial cell and platelet activation. [71][72][73] Vitamin A and D deficiencies have been shown…”

“…The discovery of novel immunomodulating therapies is exciting but we must not neglect the basic biology of nutrition, vitamins, and essential elements. Vitamin D deficiency can lead to abnormal complement activation and cause endothelial injury 69,70 . Vitamins D, A, C can also influence endothelial cell and platelet activation 71–73 .…”

High-Dose Vitamin D Supplementation Significantly Affects the Placental Transcriptome

“…Reflecting the heterogeneity of the samples evident from the PCA, only six genes were, however, identified as differentially expressed following false discovery correction at 10% (Figure 2 and Supplementary Table S1). Interestingly, these six genes included PTH, encoding the parathyroid hormone-a key regulator of the vitamin D metabolism [33]-and C2 encoding the complement component 2, a regulator of the complement system which has previously been connected to vitamin D status [34]. Further supporting the existence of a functional connection, an enrichment analysis of the transcription factor binding site in the promotor sequence of nominally significant DEGs compared to non-DEGs showed the most signifi-cant enrichment for the binding site of the Vitamin D-binding protein (VDBP) (p = 0.004).…”

“…differentially expressed following false discovery correction at 10% (Figure 2 and Supple-mentary Table S1). Interestingly, these six genes included PTH, encoding the parathyroid hormone-a key regulator of the vitamin D metabolism [33]-and C2 encoding the complement component 2, a regulator of the complement system which has previously been connected to vitamin D status [34]. Further supporting the existence of a functional connection, an enrichment analysis of the transcription factor binding site in the promotor sequence of nominally significant DEGs compared to non-DEGs showed the most significant enrichment for the binding site of the Vitamin D-binding protein (VDBP) (p = 0.004).…”