Higher Levels of 2 Autoantibodies Could Help Diagnose CTEPH and PAH, Study Suggests

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) have higher serum levels of antibodies against the EDX2 and PHAX proteins, according to research which suggests that these autoantibodies could be used as diagnostic tools for both diseases.

The study, “Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension,” was published in the journal PLOS ONE.

Although factors such as infection, inflammation, and genetic susceptibility may play a role in CTEPH development, specific and non-invasive biomarkers have not been identified.

Circulating autoantibodies have been detected in cardiovascular diseases, including atherosclerosis and coronary artery disease. However, the presence of autoantibodies in CTEPH and PAH patients has not been thoroughly explored.

Therefore, a research team from Chiba University and the Kashiwado Memorial Foundation, in Japan, used a protein array — a method to assess interactions between proteins — to analyze the levels of autoantibodies in the serum of patients with CTEPH and PAH. Serum samples were collected from patients diagnosed with these diseases at Chiba University Hospital between 2001 and 2015.

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The team first identified 34 proteins in the blood that were strongly recognized by antibodies in patients with CTEPH, compared with healthy volunteers. Researchers then predicted 63 sites recognized by the antibodies (epitope sites) in the 34 proteins selected.

These 63 epitopes were then used to analyze antibody levels in blood samples from 48 additional CTEPH patients and 48 healthy donors. Results showed that the serum levels of autoantibodies against four specific peptides seemed higher in CTEPH patients.

Of these, the levels of antibodies against EXD2 and PHAX were significantly higher in CTEPH patients in a subsequent screening.

The team then analyzed possible correlations between the antibody levels and clinical data of the patients. They found that the levels of antibody against EXD2 had a mild negative correlation with arterial oxygen pressure in CTEPH patients, meaning that higher antibody levels were associated with lower arterial pressure.

Also, the levels of this antibody decreased after successful pulmonary endarterectomy — a surgery to remove blood clots from the pulmonary arteries, which is often performed on CTEPH patients.

Similar to CTEPH patients, the serum antibody EXD2 and PHAX levels were also higher in 65 patients with PAH, particularly those with idiopathic PAH and PAH associated with connective tissue disease, which suggests that “EXD2 and PHAX may be markers associated with PH in general,” the researchers wrote.

“In conclusion, patients with CTEPH and PAH had higher titers for autoantibodies to EXD2 and PHAX,” the team wrote.

“Further investigations focused on the production of these autoantibodies might give us information on the etiology of CTEPH and PAH, as well as prove the utility of these autoantibodies as a new diagnostic tool,” they added.