Usefulness to quantify serum KL-6 levels to follow up uveitic patients with sarcoidosis

Background: KL-6 is a human glycoprotein secreted by type II alveolar cells in lung, and its serum levels increase in pneumonia of various causes. We previously reported that serum KL-6 levels in the uveitis patients with sarcoidosis were significantly higher than that of other uveitis and healthy controls. And combined measurement of serum KL-6 and angiotensin converting enzyme (ACE) was useful to screen uveitic patients to diagnose sarcoidosis. The purpose of the present study is to investigate the clinical usefulness of quantifying serum KL-6 levels for following up the patients with sarcoidosis. Patients & Mathods: Sera were obtained from 36 uveitic patients diagnosed as sarcoidosis and same number of healthy volunteers. To examine the influence of systemic medication, we collected blood samples from four more sarcoidosis patients additionally, who were systemically treated with corticosteroid or angiotensin converting enzyme (ACE) inhibitor, an anti-hypertensive drug. Serum concentration of KL-6 was measured by a human KL-6 electrochemiluminescence immunoassay (ECLIA). Results: The mean KL-6 concentrations of sarcoidosis patients and healthy controls were 449.3 ± 66.3 (mean ± SE) and 192.1 ± 11.3, respectively. The average levels of serum KL-6 were significantly elevated in sarcoidosis than helthy control subjects (p<0.001), and there were significant correlations between serum KL-6 and ACE levels in the patients with sarcoidosis (r=0.70 and p<0.0001). Moreover, serum KL-6 concentrations were less affected by systemic corticosteroid, and unaffected by ACE inhibitory drugs in contrast to ACE levels. Conclusions: Measurement of serum KL-6 in the uveitic patients may be useful to follow up the diagnosed sarcoidosis as well as diagnosing sarcoidosis, because the serum KL-6 level was correlated to ACE well, and less affected by systemic medication than ACE levels. 2 Introduction KL-6 (Krebs von den Lungen-6) is a high molecular weight mucinous glycoprotein discovered as pulmonary adenocarcinoma-related antigen, and KL-6 monoclonal antibody reacts to sugar moiety of MUC-1 [22]. MUC-1 mucin exists in mucosal epithelium of the respiratory and digestive systems, as well as epithelial cells of cornea and conjunctiva [12]. It was reported that the biochemical properties of KL-6 are similar to those of other MUC-1 mucins [10]. In normal lung tissue, KL-6 appears on type II pneumonocytes, respiratory bronchiolar epithelial cells, and bronchial gland cells [22]. Today, it is classified as Cluster 9 antigen (MUC-1) under the pulmonary cell antigen cluster classification, proposed at the 3rd International Workshop on Lung Tumor and Differentiation Antigens [30]. Measurement of serum KL-6 levels is now widely accepted in Japan as a diagnostic examination to monitor the activity of lung diseases, such as idiopathic interstitial pneumonia [21], radiation pneumonia [5], pneumonia following bone marrow transplantation [1], Pneumocystis carinii pneumonia in the immunocompromised host [6], pediatric respiratory diseases [11, 26], breast cancer [29], Amiodarone-induced pulmonary toxicity [3], Mycoplasma pneumonia [27], interstitial pneumonia associated with collagen diseases [25], and pulmonary sarcoidosis [21], Also, we recently demonstrated that serum KL-6 levels are