Clinical Significance of Serum Levels of a Carbohydrate Antigen, Sialyl SSEA-1, in Patients with Fibrosing Lung Disease

Abstract

Serum levels of sialyl SSEA-1 antigen, a carbohydrate antigen, were measured by radioimmunoassay in 142 patients with nonmalignant lung diseases. In 20 of 41 patients with fibrosing lung disease, either idiopathic or associated with collagen disease, the serum sialyl SSEA-1 levels were abnormally elevated. In patients with other lung diseases, the serum levels were almost within normal limits, less than 38.0 units/ml. In fibrosing lung disease the serum levels ranged from 13.8 to 147.0 units/ml and were largely concurrent with the degree of disease activity. The therapeutic effects of corticosteroid, which were evaluated with clinical-radiographic-physiologic scores and survivals in the patients with elevated serum levels, were significantly lower than those of the patients with the normal range of antigen levels. An immunohistochemical study performed on autopsied lungs from five patients with fibrosing lung disease indicated that the antigen was selectively expressed in the pulmonary epithelial cells that covered the remodeling alveolar septi in the lungs. No antigen was detectable by immunostaining in normal pulmonary epithelium among five normal lungs. From these findings, it is thought that the elevated levels of serum sialyl SSEA-1 may be derived from proliferating epithelial cells that were dominant in the late stage of fibrosing lung disorders. The measurements of serum sialyl SSEA-1 in patients with fibrosing lung disease may be clinically useful in establishing the degree of disease activity that has an influence on patient prognosis and therapeutic response.

Serum sialyl Lewis X-i antigen in lung adenocarcinoma and idiopathic pulmonary fibrosis

“…However, the carbohydrate antigens including sialyl Lewis X-i antigen are also increased in some patients with nonmalignant lung diseases such as IPF without coexistent malignancy. [8][9][10][11][12] There is as yet no test to make a specific diagnosis in patients with raised levels of the antigen. When increased serum levels of the antigen are found in patients with IPF without a suspicious mass on the chest CT scan, further invasive and costly tests are often considered to rule out adenocarcinoma originating from other organs.…”

“…[3][4][5][6][7] Serum levels of the carbohydrate antigens are, however, also raised in some patients with non-malignant lung diseases such as idiopathic pulmonary fibrosis (IPF), bronchiectasis, and diffuse panbronchiolitis without coexistent malignancy. [8][9][10][11][12] IPF is defined as diffuse interstitial pulmonary fibrosis of unknown aetiology which has a chronic progression. [13][14][15][16] In patients with IPF the incidence of lung cancer is much higher than that in the general population 17 so, when increased serum levels of the antigen are seen in patients with IPF, further invasive and costly tests are often undertaken to rule out adenocarcinoma of the lung or other organs.…”

Serum biomarkers in interstitial lung diseases

“…Elevated circulating levels of these antigens have been associated with neoplastic transformation and metastases and therefore been used as tumor markers in the diagnosis of lung adenocarcinoma [34,35]. Serum levels of carbohydrate antigens have been found, however, also raised in some patients with non-malignant lung diseases such as IPF [36], tuberculosis [37] and diffuse parabronchiolitis [38] and moreover immunohistochemical analysis demonstrated their presence in the hyperplastic bronchiolar epithelium, on the surface epithelium cells and on exudates in air space. Repeated damage to the lungs may force these antigens into the blood circulation resulting to the elevated serum levels of these markers detected in these patients.…”

Spatiotemporal Immunolocalization of Stage-Spacific Embryonic Antigen-1 and Related Antigens in the Developing Trachea and Lung of Fetal Hamsters.

“…Since this antigen is a ligand of endothelial cell adhesion molecules and positive immunostaining was only seen during the fetal period, this oncodevelopmental antigen may play a significant role in alveolar differentiation/determination. In human lung fibrosis, regenerating epithelium shows positive immunoreactivity for sialyl SSEA-1 [26], and the expression of the antigen is also supposed to function in reconstructing alveolar epithelial-endothelial relationships. Although 4-day culture did not allow the lung tissue to differentiate into alveolar cells, peripheral developing epithelium showed stronger staining than did stem epithelium.…”