The prognostic value of Krebs von den Lungen-6 and surfactant protein-A levels in the patients with interstitial lung disease

Abstract

Background and Objectives The highly variable clinical course of interstitial lung disease (ILD) makes it difficult to predict patient prognosis. Serum surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) are known prognostic biomarkers. However, the clinical or pathophysiological differences in patients with these biomarkers have not been well evaluated. We investigated the clinical and pathophysiological differences through the comparison of SP-A and KL-6 levels before and after treatment. Methods This study included retrospective data from 91 patients who were treated for ILD between August 2015 and September 2019. Serum SP-A and KL-6 levels were measured before and after treatment. The patients were followed up for 3 months. Results Changes in the serum biomarkers (Delta SP-A and Delta KL-6) were found to be significantly correlated (rs = 0.523, P < 0.001); Delta SP-A and Delta KL-6 were inversely correlated with changes in pulmonary function (% predicted values of diffusing capacity for carbon monoxide [DLCO], forced vital capacity [FVC], and forced expiratory volume in 1 s [FEV1]). Patients were divided into four groups based on their Delta SP-A and Delta KL-6 levels in a cluster analysis (G1, G2, G3, and G4). Both SP-A and KL-6 were elevated in the G1 group, with all the patients enrolled classified as progressive or unchanged, and 86.4% of patients showed improved disease activity in the G4 group, where both SP-A and KL-6 levels were reduced. In the G2 group, only SP-A levels decreased post-treatment, indicating an improvement in respiratory function; the patients were not at the end stage of the disease. Only the SP-A levels increased in the G3 group with immunosuppressive treatment. Conclusions Reduced serum SP-A and/or KL-6 levels are associated with improved lung function in patients with ILD. Some patients only showed a decrease in SP-A levels could prognosis an improvement in respiratory function. When only SP-A is increased, it may imply that the patients are at an early stage of disease progression. As a result, for proper disease monitoring, measuring both markers is important.

Comprehensive succinylome analyses reveal that hyperthermia upregulates lysine succinylation of annexin A2 by downregulating sirtuin7 in human keratinocytes

“…[35][36][37] Although it is well documented that ubiquitination and phosphorylation are increasingly associated with antiviral responses, the role of succinylation and other modifications in antiviral activity are still poorly understood. [38] SIRT7 exhibits desuccinylase activity in histones and maintains chromatin compaction and genome stability. [18] The expression of SIRT7 was significantly decreased after hyperthermia.…”

Exploring the Role of Biomarkers Associated with Alveolar Damage and Dysfunction in Idiopathic Pulmonary Fibrosis—A Systematic Review

“…Increased values of KL-6 in the serum are also present in other ILDs, tuberculosis, or malignant diseases (lung or breast cancer) [22,23,96]. A serum KL-6 threshold of 500U/mL has been applied to differentiate between patients affected by ILD and subjects who are apparently healthy or suffer from other pulmonary diseases unrelated to ILD [97]. At the same time, some authors consider that the serum KL-6 level might indicate the degree of injury of the epithelium of the alveoli rather than the progression of the disease [98].…”

Targeting Progression in Pulmonary Fibrosis: An Overview of Underlying Mechanisms, Molecular Biomarkers, and Therapeutic Intervention

“…The role of KL-6 as a therapeutic biomarker during IPF acute exacerbations has been tested in AE-IPF patients treated with a high dose of corticosteroids; the survived patients presented a reduction in KL-6 levels [77]. Likewise, KL-6 might predict ILD patients who may benefit better from antifibrotic therapies [79].…”