Testing iron protein in blood may improve AAV monitoring and care
Levels of transferrin may be useful marker for tracking disease activity
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Blood levels of transferrin (Tf), a protein that transports iron in the body, may serve as a useful biomarker for tracking the activity, treatment response, and outcomes of ANCA-associated vasculitis (AAV).
That’s according to a new study by researchers in China that found that individuals with active AAV had markedly lower transferrin levels — as seen in blood tests — than patients in remission or healthy individuals. Such lower Tf levels were associated with more severe inflammation and poorer kidney function, as well as reduced rates of remission and survival, the scientists noted.
“Low transferrin levels indicate poor prognosis in patients with ANCA-associated vasculitis,” the researchers wrote. “Our results indicate that [blood] Tf levels are decreased in patients with AAV and are associated with adverse clinical outcomes.”
Using Tf as a biomarker may help in improving AAV care, the team noted.
“These findings suggest that Tf may hold significant value in clinical assessment and disease monitoring,” the scientists wrote.
The study, “Association of transferrin levels with clinical outcomes in ANCA-associated vasculitis,” was published in the journal Clinical Rheumatology.
AAV is caused by the production of self-targeting antibodies called ANCAs, which abnormally activate neutrophils, a type of immune cell. This triggers inflammation in neighboring small blood vessels, leading to organ damage, particularly of the lungs and kidneys.
Tf levels were significantly lower in those with active AAV
Tf is a protein in the blood that carries and delivers iron to tissues and cells throughout the body. It is also a so-called negative acute-phase protein, meaning its levels fall, rather than rise, during inflammatory responses.
According to the researchers, however, “systematic research on dynamic changes of Tf in AAV, and their associations with disease activity and clinical outcomes remains limited.”
To fill this knowledge gap, scientists from Shanghai Jiao Tong University School of Medicine retrospectively analyzed the medical records of 162 AAV patients who had blood test results for Tf and a two-year follow-up. Among them, 130 had active disease and 32 were in remission.
The study also included 32 healthy individuals and 67 people with two other types of bodywide vasculitis, or blood vessel inflammation: 34 with Behcet’s disease and 33 with large blood vessel vasculitis.
Overall, the mean blood Tf levels were significantly lower in AAV patients than in those with other types of body-wide vasculitis, the researchers found.
Within the AAV group, those with active disease had significantly lower mean Tf levels than those in remission (161.12 vs. 225.16 mg/dL), and the remission group had significantly lower levels than healthy controls (225.16 vs. 279.84 mg/dL). Following treatment, mean Tf levels in AAV patients rose significantly, the data showed.
Tf performed well at distinguishing AAV patients with active disease from those in remission. The iron transport protein had a sensitivity — the ability to correctly identify active AAV patients — of 93.75%. Its specificity, or ability to correctly rule out those without active disease, was 75.38%.
Blood Tf levels also showed strong ability to discriminate AAV patients in remission from healthy controls, with a sensitivity of 71.88%, and a specificity of 90.63%.
Moreover, the protein “showed superior discriminative ability compared” with other standard blood-based AAV markers, the researchers noted.
The Tf test’s discriminative potential outperformed that of ESR, or erythrocyte sedimentation rate, a measure of inflammation, and C-reactive protein (CRP), another inflammation marker. It also was superior to creatinine, a measure of kidney function, and immune cell counts.
Low iron transport protein levels tied to worse outcomes
Among those with active AAV, Tf levels were significantly lower in those with impaired kidney function, low red blood cell counts due to chronic kidney disease, fever, lung involvement, or elevated blood pressure in the lungs.
Further statistical analyses showed that low Tf levels were significantly associated with elevated levels of several markers of inflammation, including ESR, CRP, and more severe kidney and lung disease.
Conversely, low Tf levels were significantly linked with reduced kidney function and low levels of other markers. These included hemoglobin, the oxygen-carrying protein in red blood cells, and total iron-binding capacity, a measure of how much iron the blood can carry.
Following those results, the researchers divided the AAV patients into a low-Tf group and a high-Tf group, based on a cut-off value of 161.12 mg/dL. The two groups differed significantly across many factors, including age, immune cell count, red blood cell count, hemoglobin, CRP, ESR, creatinine, and total iron-binding capacity. They also differed in their Birmingham Vasculitis Activity Score, which serves as a validated measure of disease activity.
Total iron-binding capacity showed the strongest ability to differentiate between the two groups, with an accuracy of 93.54%.
These findings suggest that [blood] Tf not only reflects disease activity but may also be closely associated with long-term clinical outcomes, providing valuable information for prognostic assessment in AAV.
Over a two-year follow-up period, patients in the low Tf group experienced worse outcomes than those in the high Tf group, including significantly lower overall survival, the researchers noted. Among those still living, there were higher rates of kidney failure and lower rates of disease remission.
A statistical analysis that accounted for potentially influencing factors confirmed that Tf was an independent predictor of death and remission. Adding Tf levels to a model combining creatinine and CRP to estimate the risk of death significantly improved its predictive performance.
“These findings suggest that [blood] Tf not only reflects disease activity but may also be closely associated with long-term clinical outcomes, providing valuable information for prognostic assessment in AAV,” the team wrote.
