Soluble IL-7R alpha in blood seen as possible biomarker of AAV activity

Higher levels of receptor protein portion tied to less active disease

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Higher blood levels of soluble interleukin 7 receptor subunit alpha (sIL-7R alpha) — a portion of a receptor protein involved in inflammation — significantly associate with lower disease activity in people with ANCA-associated vasculitis (AAV), a small study found.

These preliminary findings suggest that the soluble receptor protein “can be an additional and useful biomarker for assessing the simultaneous activity or predicting future negative changes in activity in patients with AAV,” the researchers wrote.

The study, “Serum soluble interleukin-7 receptor alpha levels are negatively correlated with the simultaneous activity of antineutrophil cytoplasmic antibody-associated vasculitis,” was published in Clinical and Experimental Rheumatology.

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Study involving 60 people with various types of ANCA-associated vasculitis

AAV is an autoimmune disease marked by inflammation and damage to small blood vessels. The disease is caused by the production of self-reactive antibodies called anti-neutrophil cytoplasmic antibodies or ANCAs that lead immune cells to mistakenly attack cells lining the blood vessels.

Disease activity or severity can be measured using the Birmingham Vasculitis Activity Score (BVAS), in which higher scores indicate greater disease activity. However, it would be useful to identify a biomarker in the blood, or other bodily fluid, that could reflect disease activity and response to treatment.

A team of researchers in the Republic of Korea may have identified one such biomarker.

IL-7 is a pro-inflammatory molecule that exerts its actions by binding to a receptor protein, called IL-7R, located at the surface of immune cells. The receptor is made up of two components: IL-7 receptor alpha-chain and common cytokine receptor gamma-chain.

Both IL-7 and IL-7R alpha have been implicated in the development of several autoimmune diseases. A soluble form of IL-7R alpha, which forms when the protein receptor is cut off from the surface of cells, can also be detected in blood, but its role “remains controversial,” the researchers wrote.

The molecule may either reduce or promote IL-7 activity. Previous studies in rheumatoid arthritis, another autoimmune disease, suggested sIL-7R alpha can be used as a biomarker of inflammation, since certain cells release it in response to pro-inflammatory molecules.

The researchers investigated whether blood sIL-7R alpha levels could reflect AAV activity, as assessed with BVAS.

They drew on data from 60 AAV patients in the Severance Hospital ANCA-associated Vasculitides cohort, a study following people with all types of AAV. A total of 29 patients had microscopic polyangiitis, 19 had granulomatosis with polyangiitis, and 12 had eosinophilic granulomatosis with polyangiitis.

At study’s start, patients’ mean age was 63, and 21 (35%) were women. For most of them (75%), the disease has been newly diagnosed, while for 15 patients (25%), their disease had relapsed.

Patients’ blood was drawn at two points in time: at the highest BVAS score before treatment initiation (early high) and at the lowest BVAS score after treatment (late low).

A median of 13.5 months separated the early high to late low timepoints, and the median BVAS score in the early high point was 7.5 points higher than that in the late low point (11.5 vs. four points).

Lower BVAS scores significantly linked with higher sIL-7R alpha levels

In turn, blood levels of sIL-7R alpha were significantly lower in the early high point than in the late low point (15.2 vs. 18.2 nanograms per milliliter). This tendency was observed across all AAV types.

Notably, higher sIL-7R alpha levels were significantly associated with lower BVAS scores, indicating less disease activity. When looking at specific scale domains, this significant link was observed for BVAS’ general and nervous system domains.

Lower blood sIL-7R alpha levels also showed a significant link to a faster erythrocyte sedimentation rate and higher levels of C-reactive protein — two markers of ongoing inflammation in the body.

When the researchers analyzed potential differences in the proportion of immune T-cells carrying surface-bound IL-7R alpha, they found that it was significantly lower in the early high point (62.6% vs. 78.6%).

This difference was even greater when looking at a specific type of T-cells called cytotoxic, meaning they have the ability to kill infected, cancer, and foreign cells (29.5% vs. 63.9%).

Blood sIL-7R alpha levels in patients at the early high point also were significantly lower than in 60 healthy people (15.2 vs. 27.1 nanograms per milliliter).

These findings suggest that higher levels of IL-7 in circulation “may provoke major organ damages as a proinflammatory [molecule], leading to an increase in BVAS, and may paradoxically act as a suppressor” and lower the production of membrane-bound and soluble IL-7R alpha, the team wrote.

“Our results offer new insights into the potential immunological role of [sIL-7R alpha] in AAV and provide novel biomarkers of disease activity in AAV,” the researchers concluded.