Blood GFAP levels linked to AAV disease activity, kidney involvement
Findings point to protein as possible biomarker to predict disease course
Low blood levels of glial fibrillary acidic protein (GFAP) are linked to more active disease and a higher risk of kidney failure in newly diagnosed ANCA-associated vasculitis (AAV), a study finds.
The findings point to GFAP as a potential blood biomarker to predict the course of AAV early and tailor treatment.
“Although further validation is required, we propose that [blood] GFAP could serve as a valuable complementary biomarker for newly diagnosed AAV patients, particularly those with suspected [kidney] involvement,” wrote researchers in South Korea.
The study, “Serum Glial Fibrillary Acidic Protein Can Predict Cross-Sectional Vasculitis Activity by Reflecting Renal Involvement in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis,” was published in Medicina.
In the autoimmune condition AAV, inflammation in small blood vessels leads to damage and symptoms in the kidneys and other organs. Most cases are associated with the production of self-reactive antibodies, called ANCAs.
GFAP is most abundant in the brain and spinal cord, where it’s part of the structure that helps certain cells maintain their shape. Because it can be shed into the bloodstream with nervous system damage, it’s been used as a biomarker of neurological diseases.
“Interestingly, GFAP has also been detected in non-neurological tissues such as the kidneys, skin, and liver, suggesting that [blood] GFAP could potentially serve as a biomarker for AAV by reflecting inflammation in these affected organs,” the researchers wrote.
Link between GFAP, AAV disease activity
To test this, they analyzed blood GFAP levels and their potential link to disease activity and kidney involvement in 74 AAV patients (42 women, 32 men), who were diagnosed at a median age of 63.5. Regarding the AAV types, nearly half (47.3%) had microscopic polyangiitis, 31.1% had granulomatosis with polyangiitis, and 21.6% had eosinophilic granulomatosis with polyangiitis.
At their diagnosis, the patients’ median GFAP blood levels were 259.4 picograms per milliliter (pg/mL). Disease activity was measured using the Birmingham Vasculitis Activity Score (BVAS), where a higher score indicates more active disease. The’ median BVAS at diagnosis was 5 points.
Most patients were treated with glucocorticoids (98.6%), which are anti-inflammatory and immunosuppressive medications. Cyclophosphamide (63.5%) was another commonly used immunosuppressant, followed by azathioprine (60.8%).
Over a median follow-up of a little more than two years, six patients (8.1%) died and 17 (23%) developed kidney failure.
Lower blood levels of GFAP at diagnosis were significantly linked to higher BVAS, indicating more active disease, and to higher blood levels of C-reactive protein, a biomarker of inflammation. Lower GFAP levels were also significantly associated with higher scores in BVAS’ general manifestation item, kidney manifestation, and two minor items of kidney involvement, high urine levels of protein (proteinuria) and blood (hematuria), indicating more severe kidney problems.
A GFAP cutoff value of 194.9 pg/mL at diagnosis could predict progression to kidney failure with a sensitivity of 73.7% and a specificity of 52.9%, further statistical analyses showed. A test’s sensitivity is its ability to correctly identify those people with a given condition, while its specificity refers to correctly identifying those without it.
A significantly greater proportion of patients with GFAP levels at or below the cutoff value had kidney failure during follow-up over those with higher levels (37.5% vs. 16%).
Furthermore, having GFAP levels up to 194.9 pg/mL at diagnosis was significantly linked to a more than three times higher risk of progression to kidney failure during follow-up, suggesting GFAP levels at diagnosis could represent a blood biomarker to predict disease activity and the risk of complications.
“This study is the first to demonstrate that [blood] GFAP at diagnosis can predict … vasculitis [blood vessel inflammation] activity by reflecting the extent of [kidney] involvement in patients with AAV,” wrote the researchers, who noted the data also suggest blood GFAP levels at diagnosis “could potentially, albeit partially, predict progression to [kidney failure] during follow-up in these patients.”
“Future research on GFAP could focus on its ability to track disease progression in vasculitis, its broader utility across different forms of vasculitis, and its potential as a predictor of therapeutic response,” they wrote.
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