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Soluble Macrophage Biomarkers Indicate Inflammatory Phenotypes in Patients with Knee Osteoarthritis
Hikmat N. Daghestani, PhD1,2; Carl F. Pieper, DPH3; and Virginia B. Kraus, MD, PhD1,2* Affiliations: 3 Duke Molecular Physiology Institute1, Departments of Medicine2 and Biostatistics and
Bioinformatics3, Duke University School of Medicine, Durham, NC
*Address correspondence to Virginia B. Kraus, MD, PhD, Duke Molecular Physiology
Institute, PO Box 104775, Carmichael Building, 300 N. Duke St., Durham, NC 27701.
Tel: 919-681-6652; Fax: 919-684-8907; E-mail: [email protected].
Keywords: Inflammation; biomarker; knee osteoarthritis; macrophages Financial Support: EC20 scan samples were obtained with support of a grant from Lilly
USA, Inc. This work was supported by P01 AR050245 (VBK), and NIH 5T32AI007217-30
(HND).
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Supplementary Tables: Supplementary Table 1. Associations of synovial fluid CD163 and CD14 concentrations with osteoarthritis (OA) phenotypes with end-stage OA (KL4) knee samples excluded.
OA Phenotype
Synovial Fluid CD163
Synovial Fluid CD14
β* 95% CI P-value β* 95% CI P-value
Activated macrophages in joint capsulea
0.750 0.152, 1.348 0.014 0.750 -0.007, 1.508 0.052
Activated macrophages in synoviuma
1.644 0.937, 2.352 <0.0001 1.718 0.817, 2.620 0.0002
OST severitya 2.401 0.515, 4.288 0.013 2.474 0.357, 4.592 0.022
OST severityb 0.052 -0.115, 0.219 0.541 0.574 0.269, 0.880 0.0002
JSN severitya 0.653 0.356, 0.767 <0.0001 0.920 0.616, 1.225 <0.0001
JSN severityb 0.027 -0.001, 0.055 0.056 0.074 -0.048, 0.196 0.234
OST progressionb 0.064 0.024, 0.104 0.002 0.061 -0.033, 0.155 0.206
JSN progressionb 0.065 -0.014, 0.027 0.537 0.006 -0.059, 0.072 0.848 a. Etarfolatide (EC20) scan cohort, b. Prediction of Osteoarthritis Progression (POP) cohort. *Adjusted for age, gender, and body mass index. β, parameter estimate (based on CD163 and CD14 in µg/ml); 95% CI, 95% confidence interval; OST, osteophyte; JSN, joint space narrowing.
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Supplementary Table 2. Association of serum CD163 and plasma CD14 concentrations with osteoarthritis (OA) phenotypes with end-stage OA (KL4) knee samples excluded.
OA Phenotype
Serum CD163
Plasma CD14
β* 95% CI P-value β* 95% CI P-value Activated
macrophages in joint capsulea
1.724 0.504, 2.944 0.006 0.874 0.352, 1.395 0.001
Activated macrophages in synoviuma
3.153 1.694, 4.612 < 0.0001 0.916 -0.221, 2.052 0.114
OST severitya 1.405 -3.459, 6.270 0.571 -0.173 -2.150, 1.803 0.864
OST severityb -1.001 -1.768, -0.233 0.011 0.170 -0.424, 0.764 0.575
JSN severitya 0.542 -0.077, 1.160 0.086 0.065 -0.526, 0.656 0.829
JSN severityb 0.069 -0.243, 0.381 0.666 -0.007 -0.219, 0.205 0.950
OST progressionb -0.102 -0.366, 0.162 0.450 0.103 -0.123, 0328 0.373
JSN progressionb -0.010 -0.132, 0.112 0.867 0.108 -0.012, 0.228 0.078 a. Etarfolatide (EC20) scan cohort, b. Prediction of Osteoarthritis Progression (POP) cohort. *Adjusted for age, gender, and body mass index. β, parameter estimate (based on CD163 and CD14 in µg/ml); 95% CI, 95% confidence interval; TF, tibiofemoral; OST, osteophyte; JSN, joint space narrowing.
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Supplementary Table 3. Association of CD163 and CD14 with joint symptoms with end-stage osteoarthritis (KL4) knee samples excluded.
Sample Type
CD163
CD14
β* 95% CI P-value β* 95% CI P-value
Synovial fluida 0.179 -0.213, 0.571 0.370 0.442 0.017, 0.866 0.042
Synovial fluidb -0.051 -0.126, 0.025 0.188 0.038 -0.087, 0.162 0.5525
Serum/Plasmaa 1.106 0.528, 1.683 0.0002 0.479 0.215, 0.744 0.0004
Serum/Plasmab 0.317 -0.107, 0.380 0.270 0.134 -0.125, 0.393 0.3118
a. Etarfolatide (EC20) scan cohort, b. Prediction of Osteoarthritis Progression (POP) cohort. *Adjusted for age, gender, and body mass index. β, parameter estimate (based on CD163 and CD14 in µg/ml); 95% CI, 95% confidence interval.
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Supplementary Table 4. The combinatorial effect of CD163 and CD14 with osteoarthritis phenotypes assessed by quasi-likelihood information criterion (QICu) in the Etarfolatide (EC20) scan cohort.
OST
severity JSN
severity
Activated macrophages
in joint capsule
Activated macrophages in synovium
Joint symptoms
Plasma CD14 44 44 44 44 44
Serum CD163 44 44 44 44 44
Plasma CD14 + Serum CD163 45 45 45 45 45
SF CD14 38 38 38 38 38
SF CD163 42 42 42 42 42
SF CD14 + SF CD163 39 39 39 39 39
OST, osteophyte; JSN, joint space narrowing; SF, synovial fluid. A lower QICu value indicates a more suitable model,
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Supplementary Table 5. The combinatorial effect of CD163 and CD14 with osteoarthritis phenotypes assessed by quasi-likelihood information criterion (QICu) in the Prediction of Osteoarthritis Progression (POP) cohort.
OST
severity JSN
severity OST
progression JSN
progression Joint
symptoms
Plasma CD14 311 312 249 249 290
Serum CD163 309 310 247 247 288
Plasma CD14 + Serum CD163 310 311 248 248 289
SF CD14 175 175 135 135 161
SF CD163 174 174 131 131 156
SF CD14 + SF CD163 159 159 122 122 145
OST, osteophyte; JSN, joint space narrowing; SF, synovial fluid. A lower QICu value indicates a more suitable model,