Measuring ANCA Levels in Sputum May Improve EPGA Diagnosis, Management, Study Suggests

Most patients with eosinophilic granulomatosis with polyangiitis (EGPA) test positive for anti-neutrophil cytoplasmic autoantibodies (ANCAs) in sputum samples, even if they show no signs of them in their blood, researchers from Canada and the United States found.

These patients have more severe lung involvement, the study shows, suggesting that measuring ANCA levels in sputum may offer some diagnostic value.

The study, “Sputum ANCA in serum ANCA-negative eosinophilic granulomatosis with polyangiitis (eGPA),” was published in the American Journal of Respiratory and Critical Care Medicine.

EGPA is a kind of small vessel inflammatory disease caused by the overproduction of ANCAs. In up to 60 percent of patients, however, ANCAs are undetectable in the blood.

Because the disease mainly affects the lungs, the researchers in this study hypothesized that sputum could serve as a better candidate for ANCA testing, especially in those whose lungs have been severely affected.

To test this, they examined serum and sputum samples from 23 EGPA patients and compared them with those from 19 patients with severe asthma and 13 healthy controls.

Consistent with prior findings, only 44% of EGPA patients tested positive for ANCAs in their serum. Of those 10 patients, seven were also positive for sputum-ANCAs.

Interestingly, sputum-ANCA was positive for 79% of patients who had tested negative for serum-ANCA.

Patients positive for sputum-ANCA all had respiratory symptoms, and 94% had asthma. However, only 50% of patients with negative sputum-ANCA had asthma, representing a statistically significant difference.

Researchers also found the presence of inflammatory molecules, or cytokines, specific to lung inflammation, CXCL8, CCL24, and CXCL12, in the sputum samples from positive sputum-ANCA patients.

Both of these findings strengthened the team’s hypothesis that sputum-ANCA could be a representation of increased respiratory discomfort in EGPA patients who are serum ANCA-negative, the authors wrote.

The team found that, in the laboratory, the antibodies derived from the sputum samples of ANCA-positive EGPA patients were able to form extracellular traps, an immune defense strategy characteristic of autoimmune conditions like EGPA.

“This study provides the first report of ANCA detection in sputum samples, and evidence of a possible localized autoimmune process in the airways of eGPA patients with heightened respiratory complications, irrespective of their serum ANCA status,” the authors said.

“Investigating localized autoimmunity may lead to the discovery of novel pathomechanisms, therapeutic targets, and optimal biomarkers for diagnosing and managing eGPA,” they conclude.