Elevated soluble CD226 in Takayasu arteritis is useful for differentiation from giant cell arteritis, disease activity assessment, and prognosis prediction

Abstract

Takayasu arteritis (TAK) is characterized by vascular injury, in which endothelial cells and immune cells including natural killer cells, have key roles. CD226 is an activating receptor expressed on natural killer cells and T cells, and the soluble form of CD226 (sCD226) is increased in diseases involving these cells. Therefore, we investigated the utility of serum sCD226 as a biomarker for TAK. Serum sCD226 levels were measured using an enzyme-linked immunosorbent assay in 34 TAK patients and 21 giant cell arteritis (GCA) patients. The associations between sCD226 levels and the angiographic classification, disease activity, and prognosis of TAK were analyzed. Serum sCD226 levels were significantly higher in TAK patients than in GCA patients. In patients with TAK, serum sCD226 levels were significantly elevated in the group of type Ⅴ compared with type Ⅰ to Ⅳ. Serum sCD226 levels were also elevated in patients with active TAK and in those with poor responses to corticosteroids. Moreover, the cumulative probability of relapse was increased in patients with high sCD226 levels. Serum sCD226 levels differentiated TAK from GCA and were associated with disease activity and relapse of TAK. Thus, serum sCD226 might be a useful biomarker for the management of TAK.

Keywords: Takayasu arteritis; biomarkers; disease activity; giant cell arteritis; soluble CD226.

Figure 1.

Serum sCD226 levels in patients with Takayasu arteritis and giant cell arteritis. Serum sCD226 levels were compared between patients with TAK and GCA. Each data point represents a single subject. The horizontal lines show the median. Statistical differences among groups were evaluated using the Mann–Whitney U test. GCA = giant cell arteritis, sCD226 = soluble CD226, TAK = Takayasu arteritis.

Figure 2.

Serum sCD226 levels in patients with Takayasu arteritis. Serum sCD226 levels were compared between the group of type Ⅰ to Ⅳ and type Ⅴ in TAK patients. Each data point represents a single subject. The horizontal lines show the median. Statistical differences among groups were evaluated using the Mann–Whitney U test. sCD226 = soluble CD226, TAK = Takayasu arteritis.

Figure 3.

Serum sCD226 levels in patients with Takayasu arteritis. Serum sCD226 levels were compared between active and inactive TAK patients. Each data point represents a single subject. The horizontal lines show the median. Statistical differences among groups were evaluated using the Mann–Whitney U test. sCD226 = soluble CD226, TAK = Takayasu arteritis.

Figure 4.

Serum sCD226 levels in drug-naive patients with active Takayasu arteritis. Serum sCD226 levels were compared between patients with good and poor responses to corticosteroids. Each data point represents a single subject. The horizontal lines show the median. Statistical differences among groups were evaluated using the Mann–Whitney U test. sCD226 = soluble CD226.

Figure 5.

Kaplan–Meier analysis of the cumulative probability of relapse. Curves were compared between patients with TAK having high and low sCD226 levels using log-rank tests. sCD226 = soluble CD226, TAK = Takayasu arteritis.