Semaphorin 4A as a Potential Biomarker for Diagnosis of Systemic Lupus Erythematosus

ABSTRACT

Background

Semaphorin 4A (Sema4A) is an immunoregulatory molecule that is closely related to the pathogenesis of some autoimmune diseases. However, the relationship between Sema4A and systemic lupus erythematosus (SLE) remains unknown. We therefore aimed to investigate the expression and clinical value of Sema4A in SLE patients.

Methods

Patients with SLE, rheumatoid arthritis (RA), and healthy controls (HC) were enrolled. The whole blood samples were collected from SLE (83), RA (29) and HC (85), and the expression of Sema4A on several types of leukocytes in peripheral blood was detected by flow cytometry. The serum samples were collected from SLE(77), RA (23) and HC (63), and the concentrations of soluble Sema4A in plasma were detected by ELISA. The diagnostic value of membrane-bound and soluble Sema4A in SLE patients was evaluated using a receiver operating characteristic (ROC) curve.

Results

The concentration of soluble Sema4A was significantly higher in plasma from SLE patients compared to that from HC and RA patients. In SLE patients, the ratio of CD4+CD11c+ myeloid dendritic cells (mDCs) expressing Sema4A increased significantly, and the levels of soluble Sema4A and membrane-bound Sema4A were negatively correlated with the levels of C3 and C4, respectively. The same result was observed for membrane-bound Sema4A on CD4+CD11c+ mDCs cells. In addition, the level of soluble Sema4A negatively correlated with the concentration of hemoglobin (Hb). Importantly, the expression ratio of membrane-bound Sema4A on CD4+CD11c+ mDCs was positively correlated with systemic lupus erythematosus disease activity index (SLEDAI). Finally, we revealed that soluble and membrane- bound Sema4A had high sensitivity and specificity for diagnosis of SLE, and had a greater ability to distinguish between SLE and RA.

Conclusion

Sema4A has potential as a new diagnostic biomarker for SLE, and is promising for distinguishing between SLE and RA.

KEYWORDS:

• Diagnostic efficacy
• rheumatoid arthritis
• Sema4a
• systemic lupus erythematosus

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated and analyzed during this study are included in this published article. Please contact the authors for data requests.

Ethical approval

This research was approved by Medical Ethics Committee of Affiliated Hospital of North Sichuan Medical College (File Number: 2021ER015–1).

Additional information

Funding

This work was supported by Science and Technology Project of Sichuan (2019YJ0392), Science and Technology Project of Nanchong (20SXQT0022), Research and Development Plan of North Sichuan Medical College (CBY20-QA-Z14).