Serum B-cell activating factor and lung ultrasound B-lines in connective tissue disease related interstitial lung disease

Yukai Wang; Xuezhen Xie; Shaoyu Zheng; Guangzhou Du; Shaoqi Chen; Weijin Zhang; Jinghua Zhuang; Jianqun Lin; Shijian Hu; Kedi Zheng; Angelina Mikish; Zhuangyong Xu; Guohong Zhang; Luna Gargani; Cosimo Bruni; Anna-Maria Hoffmann-Vold; Marco Matucci-Cerinic; Daniel E Furst

doi:10.3389/fmed.2022.1066111

Serum B-cell activating factor and lung ultrasound B-lines in connective tissue disease related interstitial lung disease

Front Med (Lausanne). 2022 Dec 15:9:1066111. doi: 10.3389/fmed.2022.1066111. eCollection 2022.

Authors

Yukai Wang¹, Xuezhen Xie¹, Shaoyu Zheng¹, Guangzhou Du², Shaoqi Chen³, Weijin Zhang¹, Jinghua Zhuang¹, Jianqun Lin¹, Shijian Hu¹, Kedi Zheng¹, Angelina Mikish¹, Zhuangyong Xu², Guohong Zhang⁴, Luna Gargani⁵, Cosimo Bruni⁶, Anna-Maria Hoffmann-Vold⁷, Marco Matucci-Cerinic^{6

8}, Daniel E Furst^{6

9

10}

Affiliations

¹ Department of Rheumatology and Immunology, Shantou Central Hospital, Shantou, Guangdong, China.
² Department of Radiology, Shantou Central Hospital, Shantou, Guangdong, China.
³ Department of Ultrasound, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
⁴ Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China.
⁵ Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.
⁶ Division of Rheumatology, Department of Experimental and Clinical Medicine, Careggi University Hospital, University of Florence, Florence, Italy.
⁷ Department of Rheumatology, Oslo University Hospital, Oslo, Norway.
⁸ Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Milan, Italy.
⁹ Division of Rheumatology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
¹⁰ Department of Medicine, University of Washington, Seattle, WA, United States.

Abstract

Objective: To investigate the role of serum B-cell activating factor (BAFF) and lung ultrasound (LUS) B-lines in connective tissue disease related interstitial lung disease (CTD-ILD), and their association with different ILD patterns on high resolution computed tomography (HRCT) of chest.

Methods: We measured the levels of BAFF and KL-6 by ELISA in the sera of 63 CTD-ILD patients [26 with fibrotic ILD (F-ILD), 37 with non-fibrotic ILD (NF-ILD)], 30 CTD patients without ILD, and 26 healthy controls. All patients underwent chest HRCT and LUS examination.

Results: Serum BAFF levels were significantly higher in CTD patients compared to healthy subjects (617.6 ± 288.1 pg/ml vs. 269.0 ± 60.4 pg/ml, p < 0.01). BAFF concentrations were significantly different between ILD group and non-ILD group (698.3 ± 627.4 pg/ml vs. 448.3 ± 188.6 pg/ml, p < 0.01). In patients with ILD, BAFF concentrations were significantly correlated with B-lines number (r = 0.37, 95% CI 0.13-0.56, p < 0.01), KL-6 level (r = 0.26, 95% CI 0.01-0.48, p < 0.05), and Warrick score (r = 0.33, 95% CI 0.09-0.53, p < 0.01), although all correlations were only low to moderate. B-lines number correlated with Warrick score (r = 0.65, 95% CI 0.48-0.78, p < 0.01), and KL-6 levels (r = 0.43, 95% CI 0.21-0.61, p < 0.01). Patients with F-ILD had higher serum BAFF concentrations (957.5 ± 811.0 pg/ml vs. 516.1 ± 357.5 pg/ml, p < 0.05), KL-6 levels (750.7 ± 759.0 U/ml vs. 432.5 ± 277.5 U/ml, p < 0.05), B-lines numbers (174.1 ± 82 vs. 52.3 ± 57.5, p < 0.01), and Warrick score (19.9 ± 4.6 vs. 13.6 ± 3.4, p < 0.01) vs. NF-ILD patients. The best cut-off values to separate F-ILD from NF-ILD using ROC curves were 408 pg/ml for BAFF (AUC = 0.73, p < 0.01), 367 U/ml for KL-6 (AUC = 0.72, p < 0.05), 122 for B-lines number (AUC = 0.89, p < 0.01), and 14 for Warrick score (AUC = 0.87, p < 0.01) respectively.

Conclusion: Serum BAFF levels and LUS B-lines number could be useful supportive biomarkers for detecting and evaluating the severity and/or subsets of CTD-ILD. If corroborated, combining imaging, serological, and sonographic biomarkers might be beneficial and comprehensive in management of CTD-ILD.

Keywords: B-cell activating factor; B-lines; KL-6; connective tissue disease related interstitial lung disease; high resolution CT; lung ultrasound.