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Abstract Number: 1837

KL-6, CXCL11 and CTGF Are Potential Biomarkers in Response to Treatment in CTD-ILD

Yu-Hsiang Chiu1, Mareye Voortman1, Eveline Delemarre1, Stefan Nierkens1, Pim de Jong1, Firdaus Mohamed Hoesein1, Jan Grutters2, Jacob van Laar1 and Julia Spierings3, 1University Medical Centre Utrecht, Utrecht, Netherlands, 2St. Antonius Hospital, Nieuwegein, Netherlands, 3University Medical Center Utrecht, Utrecht, Netherlands

Meeting: ACR Convergence 2021

Keywords: autoimmune diseases, Biomarkers, chemokines, cytokines, interstitial lung disease

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Session Information

Date: Tuesday, November 9, 2021

Session Title: Systemic Sclerosis & Related Disorders – Clinical Poster III (1836–1861)

Session Type: Poster Session D

Session Time: 8:30AM-10:30AM

Background/Purpose: Connective tissue disease related interstitial lung disease (CTD-ILD) is common and an important cause of morbidity and mortality. We aimed to identify biomarkers in CTD-ILD correlating with radiographic characteristics and response to immunosuppressive therapy at one-year follow-up.

Methods: An exploratory set of 38 biomarkers were measured in serum of patients with CTD-ILD at baseline and one year of follow-up. The high resolution computed tomography (HRCT) patterns were classified according to the classification for idiopathic interstitial pneumonia and categorised into fibrotic or inflammatory. The predictivity of baseline biomarker, responsiveness of biomarkers to treatment, and correlations between the variation of biomarkers and pulmonary function test after one year of treatment were examined.

Results: Sixteen patients were included (12 females (75.0%), median age 51 years (IQR 45-62). The established CTD diagnoses, comorbidities, immunosuppressive therapies, and HRCT patterns were summarized in Table 1. Patients with inflammatory HRCT patterns showed less decline in forced vital capacity (FVC), 7.7% versus 33.3% in patients with fibrotic HRCT patterns. In patients with inflammatory HRCT patterns, CXCL11 reduced from a median 307.8 pg/ml to 253.8 pg/ml (p = 0.011), CTGF from 48.5 pg/ml to 9.5 pg/ml (p = 0.033) and KL-6 from 1221 U/ml to 543 U/ml (p = 0.040). (Figure 1) Additionally, an increase in levels of galectin-3 at one-year follow-up was associated with improved FVC (Rho 0.5, p = 0.048). (Figure 1D) A visualized baseline biomarkers heatmap showed that the biomarker concentrations are determined less by ILD but more by underlying CTD manifestations. (Figure 2)

Conclusion: In this study, CXCL11, CTGF, and KL-6 reduction were associated with inflammatory HRCT patterns and better pulmonary outcome. In contrast to previous research in severe ILD, there was a positive correlation between changes of galectin-3 and FVC in our study. Further research in a larger group and focusing on combining biomarkers to predict outcome and prognosis is needed.

Table 1. Baseline demography. Abbreviations: IQR, interquartile range; CTD, connective tissue disease; HRCT, high resolution computed tomography; HSCT, hematopoietic stem-cell transplantation; LIP, lymphocytic interstitial pneumonia; MCTD, mixed connective tissue disease; NSIP, non-specific interstitial pneumonia; OP, organising pneumonia; PPFE, pleuroparenchymal fibro-elastosis; SLE, systemic lupus erythematosus; SSc, systemic sclerosis; UCTD, undifferentiated connective tissue disease; UIP, usual interstitial pneumonia.

Figure 1. Decline in CXCL11 (A), Krebs von den Lungen 6 (KL-6) (B), and connective tissue growth factor (CTGF) (C) over one year of treatment was associated with inflammatory high resolution computed tomography (HRCT) pattern. (D) Correlation between changes of Galectin_3 (Gal3) and forced vital capacity (FVC) after one year of treatment. An increase of Galectin_3 reflected the improvement of lung function.

Figure 2. Baseline biomarkers heatmap. Hierarchical clustering of biomarkers measured at baseline was visualized in the heatmap. The concentration of each biomarker was normalized and presented in colour, the closer to red the higher. MCTD, mixed connective tissue disease; SSc, systemic sclerosis; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; UCTD, undifferentiated connective tissue disease. KL6, Krebs von den Lungen 6; sICAM, soluble intercellular adhesion molecule_1; SPD, surfactant protein D; Gal3, Galectin_3; sPD1, soluble programmed death_1; sVCAM, soluble vascular cell adhesion molecule_1; YKL40, also known as chitinase 3-like 1; TNFa, tumor necrosis factor alpha; CTGF, connective tissue growth factor; Psel, P-selectin; GMCSF, granulocyte-macrophage colony-stimulating factor; MMP, matrix metalloproteinase; SAA1, serum amyloid A1; IL1RA, interleukin (IL)_1 receptor antagonist; IFNg, interferon gamma.


Disclosures: Y. Chiu, None; M. Voortman, None; E. Delemarre, None; S. Nierkens, None; P. de Jong, Sanifit, 2, Inozyme, 2; F. Mohamed Hoesein, None; J. Grutters, None; J. van Laar, Abbvie, 6, Arxx Tx, 6, Galapagos, 6, Gesyntha, 6, Leadiant, 6, Roche, 6, Boehringer Ingelheim, 5, Astra Zeneca, 5, MSD, 5, Roche, 5; J. Spierings, Boehringer Ingelheim, 5, Miltenyi, 5.

To cite this abstract in AMA style:

Chiu Y, Voortman M, Delemarre E, Nierkens S, de Jong P, Mohamed Hoesein F, Grutters J, van Laar J, Spierings J. KL-6, CXCL11 and CTGF Are Potential Biomarkers in Response to Treatment in CTD-ILD [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10). https://acrabstracts.org/abstract/kl-6-cxcl11-and-ctgf-are-potential-biomarkers-in-response-to-treatment-in-ctd-ild/. Accessed May 24, 2022.
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