Neutrophils, or called neutrocytes, are a type of white blood cells that help combat infections by bacteria, viruses, or other organisms. These cells travel to the site of infection when a pathogen invades the body, and they contain toxic chemicals that can effectively kill the pathogen. However, under certain conditions, neutrophils can also cause autoimmune diseaseas. For example, inappropriate activation of neutrophils plays a pathological role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Previous studies have implicated EMA4D (a protein that regulates immune responses) in autoimmunity. However, so fat the role of EMA4D in AAV remains elusive.
According to a study published Annals of the Rheumatic Diseases, the SEMA4D protein normally inhibits neutrophil activation. In AAV, however, the inhibition is broken down, triggering inflammation and disease. These results suggest that SEMA4D could be a biomarker and therapeutic target for AAV. The study is led by researchers from Osaka University Graduate School of Medicine, World Premier International Immunology Frontier Research Center, and AMED–CREST in Japan.
To identify the functions of SEMA4D in neutrophil activation AAV pathogenesis, the team examined blood samples from patients with AAV and healthy individuals, and wild-type and SEMA4D -/- mice neutrophils. They found that blood levels of SEMA4D were increased in AAV patients and were associated with disease activity scores. Moreover, cell-surface expression of SEMA4D was decreased in neutrophils from AAV patients. The researchers concluded that "SEMA4D has potential as a serological marker of AAV, and represents a promising therapeutic target for clinical management of neutrophil-mediated autoimmune vasculitis." (Cusabio provides EMA4D related proteins and antibodies.)