Clinical Significance of B7-H4 in Peripheral Blood of Patients With Myasthenia Gravis.

Increased mB7-H4 expression in relapsing myasthenia gravis patients may indicate disease activity, but it does not independently predict relapse risk.

Summary and findings

This study investigated changes in membrane-bound B7-H4 (mB7-H4) expression and soluble B7-H4 (sB7-H4) levels in the peripheral blood of patients with acetylcholine receptor antibodies-positive myasthenia gravis (MG) across different disease phases. The study included AchR-Ab-positive MG patients at baseline, relapse, and remission stages, along with healthy controls. Significant differences were observed in mB7-H4 expression and sB7-H4 levels between patient groups and healthy controls.

Abstract

<h4>Objectives</h4>This study aimed to systematically investigate the dynamics changes in membrane-bound B7-H4 (mB7-H4) expression and soluble B7-H4 (sB7-H4) levels in the peripheral blood of patients with acetylcholine receptor antibodies (AchR-Ab)-positive myasthenia gravis (MG) across different disease phases, and to explore their clinical significance.<h4>Methods</h4>AchR-Ab-positive MG patients at baseline, relapse, and remission stages, along with age- and sex-matched healthy controls (HCs), were enrolled. Peripheral blood was obtained from all participants. mB7-H4 expression on circulating immune cell subsets was determined by flow cytometry, while plasma sB7-H4 concentration was quantified using enzyme-linked immunosorbent assay (ELISA).<h4>Results</h4>Compared to HC, patients with relapsing MG exhibited significantly increased mB7-H4 expression on CD4⁺ T cells and CD14⁺ monocytes (p < 0.05). In contrast, plasma sB7-H4 levels were markedly decreased in relapsing-MG patients relative to HC (p < 0.05). Among MG subgroups, mB7-H4 expression on CD4⁺ T cells was significantly higher in relapsing-MG patients than in those at baseline or in remission (p < 0.05). Conversely, plasma sB7-H4 levels were significantly lower in both relapsing and remitting patients compared with the baseline-MG group (p < 0.05). Within the relapsing-MG patients, patients with abnormal thymic pathology exhibited significantly lower sB7-H4 levels than those with a normal thymus (p < 0.05). Correlation analyses demonstrated that mB7-H4 expression on CD14⁺ monocytes was positively correlated with quantitative MG scores (QMGs; r = 0.544, p = 0.020), whereas sB7-H4 levels were negatively correlated with QMGs (r = -0.417, p = 0.016). Immunosuppressive treatment did not significantly affect sB7-H4 levels compared with pre-treatment values (p > 0.05). Univariate analysis identified elevated mB7-H4 expression on CD4⁺ T cells as a potential risk factor for MG relapse. However, this association did not remain significant after multivariate adjustment for confounders variables.<h4>Conclusions</h4>During MG relapse, inflammatory activation may engage the B7-H4 pathway, characterized by increased mB7-H4 and decreased sB7-H4 levels, which may cooperatively contribute to immune suppression and serve as a compensatory protective mechanism. B7-H4 expression appears to be associated with disease severity. Thymic abnormalities may contribute to the downregulation of sB7-H4, whereas immunosuppressive treatment may not significantly modify its circulating levels. Although increased CD4⁺ B7-H4 expression is associated with relapse, it does not represent an independent predictor of relapse risk.

Key findings

• Not reported in abstract.

Limitations

• Not reported in abstract.

Elsewhere in the Thymulin (Facteur Thymique Serique) corpus