A recent study published in Medicine (Baltimore) found that elevated soluble CD226 levels in Takayasu arteritis (TAK) proved useful for differentiation from giant cell arteritis, disease activity assessment, and prognosis prediction. The investigation focused on serum sCD226 as a biomarker for TAK, a condition characterized by vascular injury involving endothelial cells and immune cells, particularly natural killer cells.
The study examined serum sCD226 levels using enzyme-linked immunosorbent assay in 34 TAK patients and 21 giant cell arteritis (GCA) patients. The analysis revealed significantly higher serum sCD226 levels in TAK patients compared to GCA patients. According to angiographic classification, within the TAK patient group, serum sCD226 levels were significantly elevated in type V classification compared to types I through IV. The findings demonstrated that serum sCD226 levels were elevated in patients with active TAK and in those showing poor responses to corticosteroid treatment. The study also identified an increased cumulative probability of relapse in patients with high sCD226 levels, suggesting prognostic value.
The research established that serum sCD226 levels successfully differentiated TAK from GCA and showed associations with disease activity and relapse patterns in TAK. The elevated serum sCD226 levels in TAK patients correlated with disease activity and disease relapse, indicating potential clinical utility for disease monitoring and management strategies.
CD226, a member of the immunoglobulin superfamily, plays a pivotal role in regulating diverse immunological processes. It is broadly expressed on both immune and non-immune cells, with predominant expression on natural killer (NK) cells and T cells. Through interaction with its ligands CD155 and CD112, CD226 activates signalling pathways that influence T cell differentiation and effector functions, while also promoting NK cell activation and cytotoxicity. Genetic polymorphisms and altered CD226 expression have been strongly linked to susceptibility to autoimmune, infectious, and allergic diseases, as well as cancer progression. Accumulating evidence underscores the potential of CD226 as a promising therapeutic target in immune-mediated disorders.
A soluble form of CD226 (sCD226), generated by shedding of the membrane-bound CD226 (mCD226) into human serum, has been identified. The potential of sCD226 as a biomarker has been reported in acute graft-versus-host disease as well as in several types of cancers. In autoimmune diseases, recent evidence demonstrated that serum sCD226 levels correlate with disease activity in rheumatoid arthritis, and are elevated in patients with active systemic lupus erythematosus, where they are further associated with both disease activity and prognosis.
The biomarker showed promise for distinguishing TAK from similar vasculitic conditions while providing insights into disease progression and treatment response patterns. Monitoring serum sCD226 levels demonstrated potential for contributing to precise clinical management of TAK patients.
References
- Nakano M, Ayano M, Fukui S, Iwanaga N, Tatsutani T, Takaki-Kuwahara A, Kimoto Y, Akahoshi M, Migita K, Kawakami A, Tada Y, Niiro H. Elevated soluble CD226 in Takayasu arteritis is useful for differentiation from giant cell arteritis, disease activity assessment, and prognosis prediction. Medicine (Baltimore). 2025 Jun 20;104(25):e42844.
- Liu K, Liu Y, Xiong H, Ning Z. The Immune Regulatory Functions of CD226 and Its Implications in Immune-Mediated Diseases. Biomolecules. 2025 Jul 14;15(7):1007.
- Mosaad YM, El-Toraby EE, Tawhid ZM, Abdelsalam AI, Enin AF, Hasson AM, Shafeek GM. Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity. Immunol Invest. 2018 Apr;47(3):264-278.
- Nakano M, Ayano M, Kushimoto K, Kawano S, Higashioka K, Inokuchi S, Mitoma H, Kimoto Y, Akahoshi M, Ono N, Arinobu Y, Akashi K, Horiuchi T, Niiro H. Association of elevated serum soluble CD226 levels with the disease activity and flares of systemic lupus erythematosus. Sci Rep. 2021 Aug 9;11(1):16162.