An analysis of the gene expression and gene pathways in different tissues affected by ANCA vasculitis has provided new information about the mechanisms involved in disease progression, a study says.
The study, “Gene Expression Pathways across Multiple Tissues in Antineutrophil Cytoplasmic Antibody-associated Vasculitis Reveal Core Pathways of Disease Pathology,” was published in the Journal of Rheumatology.
ANCA-associated vasculitis is a chronic autoimmune disease caused by antibodies called anti-neutrophil cytoplasm antibodies (ANCAs) that attack neutrophils, a type of immune cells, instead of external pathogens. When under attack, neutrophils break, causing inflammation and damage to the blood vessels.
ANCA vasculitis types are categorized depending on the organs affected. Some manifestations are multisystemic and affect various organs, as is the case of granulomatosis with polyangiitis (GPA) — affecting the lungs, kidneys, sinuses, nose, eyes, and ears — and microscopic polyangiitis (MPA), which affects the kidneys, skin, nerves, lungs, and joints.
Although it is known that ANCAs lead to the symptoms of ANCA vasculitis, the underlying mechanisms causing this immune system malfunction are unclear. Factors such as infectious diseases, medications, activation of gene networks that trigger inflammation, and genetic predisposition seem to be involved in disease development.
To test the hypothesis that there are genes and gene networks involved in all cases of ANCA vasculitis, investigators searched patterns of gene expression in samples of MPA or GPA patients that showed symptoms in different tissues, the orbit, white blood cells, and the sinuses.
Only four genes were involved in all tissues, but the researchers found 28 gene pathways — networks of genes involved in the same biological process — that were common to all tissues. These gene pathways were involved in immune responses, the interaction between blood vessel walls, cellular signaling, tissue damage and repair, infectious diseases, and platelet activation.
“This is the first analysis of gene expression pathways in common across multiple tissues in AAV (ANCA-associated vasculitis), to our knowledge,” the investigators said. “The results of our analysis support the central roles of an infectious trigger, molecular mimicry — when the body produces molecules that are so similar to molecules produced by pathogens that it triggers an immune response — and the dysregulation of (different) immune mechanisms in AAV.”
They also noted that “other pathways, (such as platelet activation and blood vessel communication), have not previously been implicated in AAV, and thus they may offer novel insights into disease pathogenesis.”
Future studies focusing on these common pathways may result in the development of new markers and therapeutic strategies for ANCA vasculitis patients.