Clinical Relevance of the Serial Measurement of Krebs von den Lungen-6 Levels in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Clinical and Laboratory Data
2.3. Trends in Serum KL-6 Level Changes
2.4. ILD Progression
2.5. Statistical Analysis
3. Results
3.1. Patient Characteristics at Baseline
3.2. Factors Associated with the Variability of Serial KL-6 Levels
3.3. Potential Utility of Short-Term KL-6 Change in Predicting ILD Progression
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Parameters | All SSc Patients (n = 110) | SSc-ILD Patients (n = 64) 1 |
---|---|---|
Sex (female) | 96 (87%) | 57 (89%) |
Age at study entry | 54 ± 13 | 53 ± 13 |
Disease duration (years) | 2.6 ± 2.0 | 2.4 ± 1.9 |
dcSSc | 46 (42%) | 33 (52%) |
SSc-related autoantibodies | ||
Anti-topoisomerase I | 45 (41%) | 33 (52%) |
Anticentromere | 31 (28%) | 10 (16%) |
Anti-U1 RNP | 11 (10%) | 8 (13%) |
Anti-RNAP III | 3 (5%) | 2 (3%) |
Anti-U3 RNP | 2 (2%) | 0 |
Anti-Th/To | 1 (1%) | 1 (2%) |
Current or past smoker | 31 (28%) | 21 (33%) |
ILD | 71 (65%) | 64 (100%) |
ILD extent shown on HRCT (%) | NA | 20.7 ± 20.9 |
Extensive disease | NA | 23 (36%) |
FVC (% predicted) 2 | 97.5 ± 17.6 | 89.8 ± 15.3 |
DLCO (% predicted) 2 | 78.5 ± 25.1 | 69.1 ± 21.8 |
CRP levels (mg/dL) | 0.14 ± 0.28 | 0.16 ± 0.29 |
KL-6 levels (U/mL) 2 | 775 ± 857 | 994 ± 899 |
Any immunomodulatory treatment during the first 2 years after diagnosis | 39 (35%) | 30 (47%) |
Clinical Parameters | β | p |
---|---|---|
Sex (female) | 0.016 | 0.866 |
Age at study entry | 0.033 | 0.733 |
Disease duration (years) | −0.186 | 0.052 |
dcSSc | 0.198 | 0.038 |
Anti-topoisomerase I | 0.241 | 0.011 |
Anticentromere | −0.256 | 0.007 |
Anti-U1 RNP | 0.089 | 0.356 |
Anti-RNAP III | 0.035 | 0.720 |
Current or past smoking | −0.065 | 0.611 |
ILD | 0.462 | <0.001 |
Disease extent shown on HRCT (%) 1 | 0.293 | 0.01 |
Extensive disease 1 | 0.358 | 0.001 |
FVC (% predicted) | −0.252 | 0.008 |
DLCO (% predicted) | −0.413 | <0.001 |
CRP levels (mg/dL) | 0.104 | 0.279 |
KL-6 levels (U/mL) | 0.369 | <0.001 |
Any immunomodulatory treatment during the first 2 years after diagnosis | 0.292 | 0.002 |
Clinical Parameters | ILD Progression (n = 12) | No ILD Progression (n = 52) | p |
---|---|---|---|
Sex (female) | 11 (92%) | 46 (88%) | 1.00 |
Age at study entry | 52 ± 14 | 53 ± 13 | 0.77 |
Disease duration (years) | 1.7 ±1.4 | 2.6 ± 2.0 | 0.17 |
dcSSc | 8 (67%) | 25 (48%) | 0.34 |
SSc-related autoantibodies | |||
Anti-topoisomerase I | 8 (67%) | 25 (48%) | 0.34 |
Anticentromere | 2 (17%) | 8 (15%) | 1.00 |
Anti-U1RNP | 2 (17%) | 6 (12%) | 0.64 |
Current or past smoker | 4 (28%) | 17 (36%) | 1.00 |
ILD extent shown on HRCT (%) | 29.6 ± 21.2 | 18.7 ± 20.4 | 0.041 |
Extensive disease | 8 (67%) | 15 (20%) | 0.020 |
FVC (% predicted) | 91.1 ± 19.6 | 89.5 ± 14.4 | 0.58 |
DLCO (% predicted) | 67.9 ± 27.0 | 69.4 ± 20.7 | 0.99 |
CRP levels (mg/dL) | 0.24 ± 0.33 | 0.14 ± 0.29 | 0.14 |
KL-6 levels (U/mL) | 1124 ± 682 | 964 ± 945 | 0.18 |
Any immunomodulatory treatment | 5 (42%) | 25 (48%) | 0.76 |
Progression of ILD | ||
---|---|---|
OMERACT Criteria 1 | PF-ILD 2 | |
KL-6 levels at baseline | 0.58 | 0.32 |
Regression coefficient over 6 months | 0.83 | 0.78 |
A ratio of the KL-6 level at 6 months to the baseline | 0.39 | 0.69 |
AUC above the standard line | 0.52 | 0.59 |
AUC above the line of baseline KL-6 levels | 0.77 | 0.31 |
Consecutive rise over 6 months | 1.00 | 0.94 |
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Shirai, Y.; Fukue, R.; Kaneko, Y.; Kuwana, M. Clinical Relevance of the Serial Measurement of Krebs von den Lungen-6 Levels in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease. Diagnostics 2021, 11, 2007. https://doi.org/10.3390/diagnostics11112007
Shirai Y, Fukue R, Kaneko Y, Kuwana M. Clinical Relevance of the Serial Measurement of Krebs von den Lungen-6 Levels in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease. Diagnostics. 2021; 11(11):2007. https://doi.org/10.3390/diagnostics11112007
Chicago/Turabian StyleShirai, Yuichiro, Ryosuke Fukue, Yuko Kaneko, and Masataka Kuwana. 2021. "Clinical Relevance of the Serial Measurement of Krebs von den Lungen-6 Levels in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease" Diagnostics 11, no. 11: 2007. https://doi.org/10.3390/diagnostics11112007