1 A 10% relative decline in FVC or a 5% to 10% relative decline in FVC and a 15% relative decline in DLCO over a 2-year period. identified as an independent factor associated with variability in KL-6 levels in different models of multiple regression analysis. We failed to demonstrate correlations between trends for KL-6 level changes during the 6 months after SSc diagnosis and ILD progression over 2 years JAK3 covalent inhibitor-1 in patients with SSc-ILD. Serum KL-6 levels fluctuate in SSc patients with JAK3 covalent inhibitor-1 ILD, especially in those with extensive disease, but the clinical utility of a serial KL-6 level measurement remains uncertain. = JAG2 110)= 64) 1 0.01 between all patients with SSc and patients with SSc-ILD. NA: not applicable; ILD: interstitial lung disease; dcSSc: diffuse cutaneous SSc; RNAP III: RNA polymerase III; RNP: ribonucleoprotein; HRCT: high-resolution computed tomography; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide; CRP: C-reactive protein, KL-6: Krebs von den Lungen-6. 3.2. Factors Associated with the Variability of Serial KL-6 Levels The distribution of serum KL-6 levels at SSc diagnosis was highly variable, ranging from 149.8 to 4251.0 U/mL. The serum KL-6 levels changed over time in a group of patients but remained stable in the remaining patients; the CV over 2 years ranged from 0.055 to 0.473. We first examined the JAK3 covalent inhibitor-1 factors associated with the CV of serial KL-6 levels in the 110 patients with SSc (Table 2). As a result, the presence of ILD, dcSSc, positive anti-topo I antibodies, unfavorable anticentromere antibodies, an increased ILD extent shown on HRCT, extensive disease, low FVC, low DLCO, a high KL-6 level at baseline and any immunomodulatory treatment were associated with a wide range of variability. Table 2 Simple regression analysis to identify the factors associated with variability of KL-6 levels over 2 years in 110 patients with SSc. = 76. ILD: interstitial lung disease, dcSSc: diffuse cutaneous SSc, RNAP III: RNA polymerase III, RNP: ribonucleoprotein, HRCT: high-resolution computed tomography, FVC: forced vital capacity, DLCO: diffusing capacity for carbon monoxide, CRP: C-reactive protein. When the SSc patients were divided into two groups based on the presence or absence of ILD, the serum KL-6 levels fluctuated over 2 years in the majority of the SSc patients with ILD (Physique 1A). In contrast, the patients without ILD showed consistently low KL-6 levels without fluctuations (Physique 1B). In the SSc patients with ILD, the fluctuations in the KL-6 levels were more prominent in the patients with extensive disease than in those with limited disease (Physique 1C,D). In addition, the CV of the serial KL-6 level changes was significantly negatively correlated with FVC and DLCO and JAK3 covalent inhibitor-1 positively correlated with KL-6 levels at baseline (Figure 2ACC). In the 76 patients who underwent chest HRCT at SSc diagnosis, there was a JAK3 covalent inhibitor-1 significant correlation between the CV of the serial KL-6 level changes and the ILD extent shown on HRCT (Figure 2D). Open in a separate window Figure 1 Longitudinal changes in serum KL-6 levels over 2 years after SSc diagnosis. (A) SSc patients with ILD; (B) SSc patients without ILD; (C) SSc patients with ILD and limited disease; and (D) SSc patients with ILD and extensive disease. Open in a separate window Figure 2 Correlations between the coefficient of variation (CV) of serial KL-6 level changes and (A) FVC, (B) DLCO and (C) baseline KL-6 levels in 110 patients with SSc or (D) ILD extent on HRCT in 76 patients who underwent chest HRCT at SSc diagnosis. The majority of.