Omalizumab stops proliferation, transformation of fibrocytes in severe allergic asthma

The anti-immunoglobulin (Ig) E therapy omalizumab lessens the number of circulating fibrocytes, cell and number of fibrocytes, and α-smooth muscle actin (α-SMA)⁺ fibrocytes after 3–7 days of culture in patients with severe allergic asthma (SAA), a study has shown.

Interleukin (IL)-33 and IL-13 are associated with the effectiveness of omalizumab in inhibiting fibrocyte activation contributing partly to the clinical benefits in reducing lamina propria and basement membrane thickening.

In this study, the investigators examined the effects of anti-IgE therapy on fibrocyte activities. They measured the expression of CCR7, CXCR4, ST2, and α-SMA in both circulating and cultured fibrocytes from all patients with asthma and repeated this after omalizumab treatment in SAA. In response to anti-IgE therapy, fibrocytes recruitment, proliferation, and transformation were also measured.

Omalizumab significantly improved asthma control and pulmonary function in T2-high SAA, as shown by a reduction in serum levels of IL-33 and IL-13. It also downregulated CXCR4 and CCR7 expressions of fibrocytes, potentially curbing fibrocyte recruitment into the lungs. In addition, omalizumab suppressed the increased number of fibrocytes and α-SMA⁺ fibrocytes within the cultured nonadherent non-T (NANT) cells after 3–7 days of culture.

The effectiveness of omalizumab in inhibiting fibrocyte recruitment, proliferation, and myofibroblast transformation through IL-33/ST2 axis was driven by the decrease in serum IL-33 levels. Moreover, the elevated IL-13 expression in SAA patients boosted the effects of IL-33 by increasing ST2 expression.

“Circulating fibrocytes act as precursors of myofibroblasts, contribute to airway remodelling in chronic asthma, and migrate to injured tissues by expressing CXCR4 and CCR7,” the investigators said. “Anti-IgE therapy improves SAA control and airway remodelling in T2-high SAA.”