Periostin Is a Biomarker of Rheumatoid Arthritis-Associated Interstitial Lung Disease
Abstract
:1. Introduction
2. Patients and Methods
2.1. Study Subjects
2.2. Study Protocol
2.3. Measurement of Periostin by ELISA
2.4. Immunohistochemical Assay
2.5. Statistical Analysis
3. Results
3.1. Patients’ Characteristics and Concordance of HRCT Evaluation between Two Investigators
3.2. ROC Analysis to Differentiate RA-ILD Patients from RA Patients without ILD or Healthy Controls
3.3. Correlation between Serum Biomarker Levels and Clinical Data of RA-ILD Patients
3.4. Immunohistochemical Assay Using Anti-Periostin Monoclonal Antibodies
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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p Value | |||||||
---|---|---|---|---|---|---|---|
Among | RA-ILD vs. | RA-ILD vs. | RA w/o ILD | ||||
RA with ILD | RA w/o ILD | Healthy Control | 3 Groups | RA w/o ILD | Control | vs. Control | |
N | 19 | 20 | 137 | ||||
Age | 70 (65–76) | 66 (60–73) | 41 (30–50) | <0.0001 * | 0.14 | <0.0001 * | <0.0001 * |
Male gender | 6 (32%) | 4 (20%) | 91 (66%) | <0.0001 * | 0.48 | 0.0050 * | 0.0001 * |
Smoker | 6 (32%) | N.D. | 64 (47%) | 0.23 | |||
LDH (IU/L) | 205.0 (178.0–233.0) | 195.0 (164.3–232.8) | 149.0 (136.0–164.5) | <0.0001 * | 0.66 | <0.0001 * | <0.0001 * |
SP-D (ng/mL) | 105.0 (50.2–203.0) | 36.1 (22.8–69.5) | 40.5 (26.7–66.3) | 0.0002 * | 0.0012 * | <0.0001 * | 0.72 |
KL-6 (IU/mL) | 1022.0 (579.0–1467.0) | 214.5 (177.3–273.0) | 274.0 (226.5–336.0) | <0.0001 * | <0.0001 * | <0.0001 * | 0.0048 * |
Monomeric periostin (pg/mL) | 15.9 (14.3–20.1) | 13.4 (10.8–16.3) | 8.3 (7.2–9.9) | <0.0001 * | 0.0043 * | <0.0001 * | <0.0001 * |
Total periostin (pg/mL) | 100.0 (77.0–140.0) | 73.5 (55.8–84.8) | 63.0 (52.5–75.5) | <0.0001 * | 0.0035 * | <0.0001 * | 0.10 |
Pulmonary Function | |
Vital capacity (%) | 84.4 (66.7–107.3) |
DLCO (%) | 71.4 (60.7–86.1) |
HRCT pattern | |
Definite UIP | 5 (25%) |
Possible UIP | 3 (15%) |
Inconsistent with UIP | 12 (60%) |
Extent of abnormal area on chest HRCT (%) | |
Normal lung area | 137.5 (100.0–155.0) |
Honeycombing | 0 (0–7.5) |
Reticulation | 25.0 (10.0–40.0) |
Ground-glass attenuation | 22.5 (20.0–47.5) |
Airspace consolidation | 0 (0–10.0) |
Fibrosis score | 25.0 (10.0–40.0) |
Inflammation score | 32.5 (20.0–50.0) |
TBE grade on HRCT | 13.0 (7.0–30.0) |
AUC | Standard Error | p Value | Cut-Off Value | Sensitivity (%) | Specificity (%) | |
---|---|---|---|---|---|---|
Distinguishing RA without ILD patients | ||||||
LDH (IU/L) | 0.459 | 0.0028 | 0.53 | 218.0 | 73.7 | 35.0 |
KL-6 (IU/mL) | 0.939 | 0.0020 | <0.0001 * | 329.0 | 100.0 | 80.0 |
SP-D (ng/mL) | 0.803 | 0.0088 | 0.0002 * | 93.9 | 63.2 | 90.0 |
Monomeric periostin (ng/mL) | 0.767 | 0.081 | 0.0089 * | 14.3 | 79.0 | 75.0 |
Total periostin (ng/mL) | 0.767 | 0.013 | 0.0027 * | 98.0 | 63.2 | 85.0 |
Distinguishing Healthy controls | ||||||
LDH (IU/L) | 0.886 | 0.0096 | <0.0001 * | 177.0 | 84.2 | 88.3 |
KL-6 (IU/mL) | 0.972 | 0.0032 | <0.0001 * | 423.0 | 89.5 | 95.6 |
SP-D (ng/mL) | 0.794 | 0.0050 | <0.0001 * | 79.5 | 68.4 | 87.6 |
Monomeric periostin (ng/mL) | 0.994 | 0.443 | <0.0001 * | 12.5 | 100.0 | 96.3 |
Total periostin (ng/mL) | 0.876 | 0.0126 | <0.0001 * | 75.0 | 84.2 | 74.0 |
Monomeric Periostin (ng/mL) | Total Periostin (ng/mL) | KL-6 (IU/mL) | SP-D (ng/mL) | LDH (IU/L) | ||||||
---|---|---|---|---|---|---|---|---|---|---|
R | p Value | R | p Value | R | p Value | R | p Value | R | p Value | |
Age (years) | 0.17 | 0.50 | 0.26 | 0.28 | −0.069 | 0.78 | −0.0053 | 0.98 | 0.19 | 0.44 |
Serum biomarkers | ||||||||||
SP-D (ng/mL) | 0.073 | 0.77 | 0.12 | 0.61 | 0.53 | 0.019 * | - | - | 0.24 | 0.33 |
LDH(IU/L) | −0.30 | 0.22 | 0.078 | 0.75 | 0.36 | 0.13 | 0.24 | 0.33 | - | - |
KL-6 (IU/mL) | 0.23 | 0.35 | 0.29 | 0.23 | - | - | 0.53 | 0.019 * | 0.36 | 0.13 |
Pulmonary function | ||||||||||
Vital capacity (%) | −0.32 | 0.19 | −0.53 | 0.022 * | −0.063 | 0.80 | −0.35 | 0.16 | −0.21 | 0.39 |
DLCO (%) | −0.18 | 0.52 | −0.38 | 0.16 | −0.50 | 0.060 | −0.45 | 0.090 | −0.31 | 0.27 |
Extent of abnormal area on chest HRCT (%) | ||||||||||
Normal lung area | −0.57 | 0.011 * | −0.62 | 0.0045 * | −0.44 | 0.062 | −0.35 | 0.15 | −0.13 | 0.58 |
Honeycombing | 0.54 | 0.018 * | 0.65 | 0.0025 * | 0.28 | 0.25 | −0.12 | 0.64 | −0.12 | 0.64 |
Reticulation | 0.51 | 0.013 * | 0.78 | 0.0002 * | 0.18 | 0.47 | 0.045 | 0.85 | 0.18 | 0.47 |
GGA | −0.031 | 0.90 | −0.14 | 0.56 | 0.44 | 0.061 | 0.54 | 0.017 * | 0.25 | 0.31 |
Airspace consolidation | 0.19 | 0.44 | 0.069 | 0.78 | −0.47 | 0.041 * | −0.26 | 0.29 | −0.41 | 0.081 |
Fibrosis score | 0.55 | 0.014 * | 0.78 | <0.0001 * | 0.18 | 0.47 | 0.051 | 0.83 | 0.11 | 0.65 |
Inflammation score | −0.091 | 0.71 | −0.13 | 0.59 | 0.25 | 0.31 | 0.31 | 0.19 | 0.14 | 0.56 |
TBE grade on HRCT | 0.47 | 0.041 * | 0.70 | 0.0008 * | 0.33 | 0.16 | 0.41 | 0.079 | 0.19 | 0.42 |
Definite UIP Pattern | p Value | ||
---|---|---|---|
Yes | No | ||
N | 5 | 14 | |
LDH (IU/L) | 200.0 (163.0–218.0) | 207.5 (180.3–262.8) | 0.19 |
KL-6 (IU/mL) | 1414.0 (554.5–1905.0) | 942.5 (541.8–1367.3) | 0.52 |
SP-D (ng/mL) | 93.9 (35.9–240.0) | 123.0 (56.7–212.0) | 0.52 |
Monomeric periostin (pg/mL) | 20.1 (18.6–50.5) | 15.3 (13.5–17.5) | 0.018 * |
Total periostin (pg/mL) | 143.0(121.9–202.5) | 90.0 (73.8–115.0) | 0.0095 * |
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Matama, G.; Okamoto, M.; Fujimoto, K.; Johkoh, T.; Tominaga, M.; Mukae, H.; Sakamoto, N.; Komiya, K.; Umeki, K.; Komatsu, M.; et al. Periostin Is a Biomarker of Rheumatoid Arthritis-Associated Interstitial Lung Disease. J. Clin. Med. 2023, 12, 7100. https://doi.org/10.3390/jcm12227100
Matama G, Okamoto M, Fujimoto K, Johkoh T, Tominaga M, Mukae H, Sakamoto N, Komiya K, Umeki K, Komatsu M, et al. Periostin Is a Biomarker of Rheumatoid Arthritis-Associated Interstitial Lung Disease. Journal of Clinical Medicine. 2023; 12(22):7100. https://doi.org/10.3390/jcm12227100
Chicago/Turabian StyleMatama, Goushi, Masaki Okamoto, Kiminori Fujimoto, Takeshi Johkoh, Masaki Tominaga, Hiroshi Mukae, Noriho Sakamoto, Kosaku Komiya, Kenji Umeki, Masamichi Komatsu, and et al. 2023. "Periostin Is a Biomarker of Rheumatoid Arthritis-Associated Interstitial Lung Disease" Journal of Clinical Medicine 12, no. 22: 7100. https://doi.org/10.3390/jcm12227100