KL-6 levels in the connective tissue disease population: typical values and potential confounders-a retrospective, real-world study

Aiyuan Zhou; Haiyun Tang; Wenzhong Peng; Yanan Wang; Xiaoping Tang; Hang Yang; Rongli Lu; Pinhua Pan

doi:10.3389/fimmu.2023.1098602

KL-6 levels in the connective tissue disease population: typical values and potential confounders-a retrospective, real-world study

Front Immunol. 2023 Jun 20:14:1098602. doi: 10.3389/fimmu.2023.1098602. eCollection 2023.

Authors

Aiyuan Zhou^{1

2

3

4

5}, Haiyun Tang⁶, Wenzhong Peng^{1

2

3

4

5}, Yanan Wang^{1

2

3

4

5}, Xiaoping Tang^{1

2

3

4

5}, Hang Yang^{1

2

3

4

5}, Rongli Lu^{1

2

3

4

5}, Pinhua Pan^{1

2

3

4

5}

Affiliations

¹ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Respiratory Medicine, Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China.
⁴ Department of Respiratory Medicine, Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China.
⁵ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
⁶ Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

Background: Krebs von den Lungen 6 (KL-6) is a potential biomarker for determining the severity of interstitial lung disease (ILD) in patients with connective tissue disease (CTD). Whether KL-6 levels can be affected by potential confounders such as underlying CTD patterns, patient-associated demographics, and comorbidities needs further investigation.

Methods: From the database created by Xiangya Hospital, 524 patients with CTD, with or without ILD, were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers, autoimmune antibodies, and the KL-6 level at admission. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. The percent of predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and computed tomography (CT) scans were used to determine the severity of ILD.

Results: Univariate linear regression analysis showed that BMI, lung cancer, TB, lung infections, underlying CTD type, white blood cell (WBC) counts, neutrophil (Neu) counts, and hemoglobin (Hb) were related to KL-6 levels. Multiple linear regression confirmed that Hb and lung infections could affect KL-6 levels independently; the β were 9.64 and 315.93, and the P values were 0.015 and 0.039, respectively. CTD-ILD patients had higher levels of KL-6 (864.9 vs 463.9, P < 0.001) than those without ILD. KL-6 levels were closely correlated to the severity of ILD assessed both by CT and DLCO%. Additionally, we found that KL-6 level was an independent predictive factor for the presence of ILD and further constructed a decision tree model to rapidly determine the risk of developing ILD among CTD patients.

Conclusion: KL-6 is a potential biomarker for gauging the incidence and severity of ILD in CTD patients. To use this typical value of KL-6, however, doctors should take Hb and the presence of lung infections into account.

Keywords: CTD; CTD-ILD; CTD-NILD; ILD; KL-6.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Connective Tissue Diseases* / complications
Connective Tissue Diseases* / epidemiology
Humans
Lung / metabolism
Lung Diseases, Interstitial* / metabolism
Retrospective Studies

Substances

Biomarkers

Grants and funding

This study was supported by grants from The Youth Science Foundation of Xiangya Hospital (2022Q06 to AZ), the Natural Science Foundation of Hunan Province, China (No. 2023JJ41025 to AZ), the Scientific Research Project of Hunan Health Commission(Grant No.D202303029041), Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, Grant No. 2020LNJJ05), The National Key Clinical Specialist Construction Program of China (Grant Number z047-02), and Key R & D Program of Hunan Province (No.2022SK2038).