GPX-3 may be blood biomarker of AAV disease activity: Study
Lower enzyme levels linked to blood vessel damage at diagnosis
Lower blood levels of glutathione peroxidase-3 (GPX-3), an antioxidant enzyme, are significantly associated with greater disease activity and blood vessel damage in people with ANCA-associated vasculitis (AAV), a study found.
“We demonstrated that [blood] GPX-3 concentration at diagnosis has the potential to be a novel biomarker that can assess and estimate activity and damage caused by AAV, although it is confined to the time of diagnosis,” the researchers wrote.
The study, “Serum glutathione peroxidase-3 concentration at diagnosis as a biomarker for assessing disease activity and damage of antineutrophil cytoplasmic antibody-associated vasculitis at diagnosis,” was published in Frontiers in Molecular Biosciences.
AAV is a group of autoimmune diseases characterized by inflammation and damage to small blood vessels in tissues in organs, most commonly the lungs, kidneys, and skin. AAV is caused in most cases by ANCAs, self-reactive antibodies that bind to enzymes in neutrophils, a type of immune cell, overly activating the cells.
Oxidative stress, a type of cellular damage that results from an imbalance between the production of potentially harmful free radicals and the cells’ antioxidant defenses, is also thought to contribute to the blood vessel inflammation and damage that marks AAV.
Disease activity and GPX-3
GPX-3 suppresses inflammatory responses and helps protect cells from oxidative stress, with its levels in the blood being considered a biomarker of inflammation severity.
While “it could be speculated that [blood] GPX-3 concentration may be inversely associated with the current degree of [blood vessel] inflammation and damage in patients with AAV, the researchers wrote, “no study has elucidated” this.
To evaluate the clinical usefulness of blood GPX-3 levels in AAV, the team of researchers at Yonsei University College of Medicine in South Korea retrospectively analyzed laboratory and clinical data from 71 newly diagnosed and untreated AAV patients followed at their university hospital.
The participants, 45 women and 26 men, had a median age of 63, and had different AAV types. Nearly half (49.3%) were diagnosed with microscopic polyangiitis, 32.4% had granulomatosis with polyangiitis, and 18.3% had eosinophilic granulomatosis with polyangiitis.
Most (57.7%) had ANCAs against the myeloperoxidase enzyme, while 15.5% had ANCAs targeting the proteinase 3 enzyme, and 4.2% had both.
Nearly one-third of the patients (32.4%) also had high blood pressure, 21.1% had type 2 diabetes, and 18.3% had abnormal levels of fats in the blood.
At diagnosis, blood GPX-3 levels were not significantly associated with patients’ sex, AAV type, ANCA type, or coexisting conditions.
However, higher blood GPX-3 levels were significantly associated with higher blood levels of hemoglobin, the protein in red blood cells that carries oxygen, and albumin, a molecule that is reduced with inflammation. Lower GPX-3 levels were significantly linked to higher levels of a marker of inflammation called C-reactive protein.
Lower blood GPX-3 levels were significantly associated with higher values in the Birmingham Vasculitis Activity Score (BVAS), reflecting higher disease activity, and the Vasculitis Damage Score (VDI), indicating greater blood vessel damage.
Based on these results, patients were divided according to the presence or absence of each of the nine organ-involvement items in the BVAS score, and their GPX-3 levels were compared.
The researchers found that while having general symptoms and/or organ-specific manifestations was generally associated with lower GPX-3 levels than their absence, these level differences only reached statistical significance for general manifestations.
“We conclude that the correlation between [blood] GPX-3 concentration and BVAS may be based on the sum of the cumulative contributions of several organ involvements … rather than that of specific organ invasion by AAV,” they wrote.
During follow-up, 17 patients (23.9%) developed kidney failure, four (5.6%) had strokes, and one (1.4%) had acute coronary syndrome, a range of conditions marked by reduced blood flow to the heart. Six patients (8.5%) died.
The team found that blood GPX-3 levels at diagnosis were not significantly associated with any of these poor outcomes or death.
“We demonstrated for the first time that [blood] GPX-3 concentration at diagnosis correlates with vasculitis activity and damage at diagnosis in patients with AAV, suggesting a possible role of [blood] GPX-3 as a complementary biomarker for assessing AAV activity in real clinical practice,” the researchers wrote.
Larger studies, following patients over time and pairing serial clinical data with blood samples, “will provide more reliable and dynamic information on the clinical significance of [blood] GPX-3 concentration for not only assessing activity and damage at diagnosis but also predicting and monitoring the prognosis during follow-up in patients with AAV,” the team concluded.
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