Progranulin Protein Levels in Blood May Predict AAV Severity

Somi Igbene, PhD avatar

by Somi Igbene, PhD |

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Blood levels of progranulin — a protein involved in cell development, cell growth, and wound healing — may predict the severity of ANCA-associated vasculitis (AAV), a new observational study suggests.

According to researchers, serum progranulin, or the protein’s levels in the bloodstream, “could be used as a predictive marker for high activity of AAV.”

The study, “Serum progranulin as a predictive marker for high activity of antineutrophil cytoplasmic antibody-associated vasculitis,” was published in the Journal of Clinical Laboratory Analysis.

Progranulin can function as either an anti-inflammatory or pro-inflammatory protein, depending on the immune response.

For instance, in systemic lupus erythematosus or SLE, the most common form of lupus, progranulin acts as a pro-inflammatory protein, encouraging the release of proteins that propagate inflammation. Conversely, in rheumatoid arthritis and psoriasis — a skin disease that causes red, itchy, scaly patches — it acts as an anti-inflammatory protein, stimulating the release of proteins that dampen inflammation.

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It remained unclear, however, how progranulin contributes to inflammation in AAV and whether it reflects the severity of AAV. Now, scientists in Korea investigated if progranulin could predict ANCA severity.

A total of 58 adults with AAV were selected from the Severance Hospital AAV cohort, a prospective and observational group of patients with different types of AAV. Among the types evaluated in this study were microscopic polyangiitis, known as MPA, granulomatosis with polyangiitis, or GPA, and eosinophilic granulomatosis with polyangiitis, called EGPA.

All participants provided demographic data, disease details including organ involvement, and blood samples to measure various biochemical markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum progranulin levels.

Participants also completed various health surveys, including the Short-Form 36-item health survey physical and mental component (SF-36 PCS and SF-36 MCS), Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and vasculitis damage index (VDI).

The median age of the patients was 63, and 32.8% were male. A total of 50% had MPA, 29.3% GPA, and 20.7% EGPA. Most of the participants had organ involvement, with the lungs (72.4%), kidneys (55.2%), and ear, nose, and throat (43.1%) being the most affected. Many participants (43.1%) also reported general symptoms.

Serum progranulin was positively linked to BVAS, FFS, ESR, and CRP levels, but negatively linked with SF-36 PCS, indicating that higher levels of progranulin seem to be associated with worse disease activity.

Protein levels in the blood also were significantly linked to patients’ general symptoms score and kidney involvement. Notably, participants with general symptoms had significantly higher median serum progranulin than participants without such symptoms. However, there was no difference in serum progranulin levels between those with and without kidney involvement.

The median serum progranulin of the patient group analyzed was 49.0 nanograms (ng)/ml. Based on calculations, the scientists defined two progranulin cut-off points — 55.16 ng/ml and 43.01 ng/ml — to predict AAV severity.

With 55.16 ng/ml as the cut-off point, predictability was more specific. However, sensitivity was greater with 43.01 ng/ml as the cut-off point. Moreover, neither cut-off could independently predict AAV severity. Despite this, serum progranulin levels higher than both 55.16 ng/ml and 43.01 ng/ml were significantly linked with severe AAV.

“We estimated the optimum cut-off value of serum progranulin for predicting severe AAV and found two cut-offs, one with high sensitivity and the other with high specificity. We demonstrated that the two cut-off values showed a significant relative risk for … severe AAV,” the researchers wrote.

One limitation of the study highlighted by the researchers was its small sample size, of just fewer than 60 participants. That led to an inability to obtain generalized conclusions that could apply to real-life settings, the team said.

“A future study with a larger cohort of AAV patients will not only validate these results but also provide more reliable information on the clinical implications of changes in serum progranulin observed in AAV patients,” the researchers wrote.

Overall, the study suggests that “progranulin might play an anti-inflammatory role in AAV,” the team concluded.