5 Genes Identified as Biomarkers in AAV-related Kidney Damage
Genetic biomarkers and immune pathways related to kidney damage in people with ANCA-associated vasculitis (AAV) were identified in a recent study.
The five identified biomarker genes may be involved in the progression of kidney damage through immune system signaling, its researchers said.
The study, “Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis,” was published in Frontiers in Immunology.
AAV is characterized by the immune system mistakenly attacking blood vessels throughout the body. While many organs can be affected, the kidneys are particularly susceptible.
AAV-associated glomerulonephritis (AAV-GN), or inflammation in the blood vessel network that filters waste from the kidneys, is a serious consequence of AAV that can result in kidney failure.
“A deeper understanding of the molecular mechanisms associated with the occurrence and progression of AAV-related kidney damage is of great significance for early diagnosis and treatment of the disease and the identification of new therapeutic targets,” the researchers wrote.
Immune pathways have been implicated in AAV progression, however their direct relationship to AAV-GN remains unclear.
To identify possible pathways that may be involved in AAV-GN, researchers in China examined differences in gene expression and immune pathways between samples from 37 AAV-GN patients and 24 healthy people serving as controls. Gene expression, also called gene activity, is the process by which information in a gene is converted to create a product, like a protein.
Genetic analyses showed that hundreds of genes had different expression levels in AAV-GN patients compared to healthy controls, with 365 genes being more highly expressed in AAV-GN, and 295 having a lower expression.
Among all the genes, five were identified as potential biomarkers for AAV-GN. Specifically, TAPBP, TMEM184B, BGN, CYP3A5, and SLC12A3 each showed strong diagnostic value, meaning their expression levels were predictive of the disease. TAPBP, TMEM184B, and BGN showed increased expression in AAV-GN, whereas CYP3A5 and SLC12A3 had decreased expression.
Of these five, TAPBP, BGN, and CYP3A5 have been previously associated with inflammatory conditions, supporting their role in AAV-GN, but the roles of TMEM184B and SLC12A3 remain to be explored, the researchers noted.
In addition, many of the 365 genes with increased expression in AAV-GN were associated with immune and inflammatory responses, supporting a role for the immune system in the progression of AAV-associated kidney disease.
An analysis of immune cell infiltration showed that several types of immune cells — including monocytes, T-cells, B-cells, and T-helper cells — are more prevalent in AAV-GN than in healthy tissues. “These results further demonstrated the crucial role played by these immune cells in the progression of ANCA-GN,” the researchers wrote.
Infiltration of several immune cell types were each correlated with higher expression of TMEM184B, TAPBP, and BGN and lower expression of CYP3A5 and SLC12A3.
This means that CYP3A5, SLC12A3, BGN, TAPBP, and TMEM184B “may be involved in the progression of ANCA-GN through immune-related signal pathways,” the researchers wrote.
“In terms of follow-up studies, prospective and large-sample studies will be used to further screen for diagnostic markers with high sensitivity and specificity for ANCA-GN to reduce invasive testing and provide a reference for early diagnosis and targeted drug research for ANCA-GN,” they concluded.