Biochemical Biomarkers of Mucosal Healing for Inflammatory Bowel Disease in Adults
Abstract
:1. Introduction
2. Methods
3. Results
3.1. Interpretative Synthesis of Data: Fecal Markers
3.1.1. Calprotectin
3.1.2. Fecal Calprotectin as a Marker of Mucosal Healing
3.1.3. Limitations of Fecal Calprotectin
3.1.4. Technical Considerations
3.1.5. Other Fecal Markers
3.2. Interpretative Synthesis of Data: Serum-Based Markers
3.2.1. C-Reactive Protein (CRP)
3.2.2. Other Acute Phase Reactants (APRs)
3.2.3. Cytokines, Their Receptors, and Growth Factors
3.2.4. Other Serum-Based Markers
3.3. Interpretative Synthesis of Data: Urine-Based Markers
4. Review Limitations
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Endoscopic Activity Indices | |||
---|---|---|---|
Parameter | MES [16] | UCEIS [21] | UCCIS [22] |
Erythema | + | ||
Granularity | + | ||
Vascular pattern | + | + | + |
Friability | + | + | + |
Erosions | + | + | + |
Ulceration | + | + | + |
Exudate | |||
MH definition | 0–1 | nd | nd |
Validation | + | + |
Authors | N MH/Total | MH Definition | Marker Performance | Assay * | ||
---|---|---|---|---|---|---|
AUC | Cutoff (µg/g) | Sens. and Spec. | Type, Manufacturer | |||
Carlsen et al. [42] | 68/106 | MES = 0 and GS ≤ 1 | 0.87 | ≤25 | 58% and 90% | ELISA, Calpro Ltd. |
Jha et al. [43] | 5/81 | MES ≤ 1 | 0.94 | 158 | 90% and 85% | ELiA, Phadia 100 Calprotectin |
Jusué et al. [32] | 30/48 | MES = 0 | 0.91 0.92 | 501 1022 | 79% and 85%1 79% and 85%2 | rapid kit, Quantum Blue®, Bühlmann 1low-range test; 2high-range test |
Mak et al. [44] | 23/61 | MES ≤ 1 | 0.78 | <250 | 77% and 67% | ELISA, Genova Diagnostics |
Mine et al. [45] | 45/60 | MES = 0 | 0.77 | 201 | 71% and 78% | EliA, Immunodiahnostik AG |
Walsh et al. [46] | 21/66 | UCEIS ≤ 1 | 0.92 | 187 | 100% and 67% | IBDoc® FCal test, Bühlmann |
Chen et al. [47] | 12/44 | MES ≤ 2 | 0.96 | ≤250 | 85% and 100% | ELISA, Bühlmann Calprotectin |
Kostas et al. [48] | 39/149 (mixed UC and CD) | MES = 0 ML absence (CD) | 0.96 | 174 | 92% and 87% | ELISA, EK CAL, Bühlmann |
Lee et al. [49] | na/181 | MES = 0 UCEIS = 0 | 0.88 | 187 | 86% and 89% | rapid test, Quantum Blue®, Bühlmann |
Patel et al. [50] | 31/60 | MES ≤ 1 | 0.92 | 60 | 86% and 87% | EliA, na |
Hiraoka et al. [51] | 75/152 | MES = 0 | 0.81 0.822 | <1841 <2242 | 78% and 69%1 79% and 78%2 | 1ELISA, Phical Calprotectin; 2LATIA |
Zittan et al. [52] | 44/58 (mixed UC and CD) | MES = 0 SES-CD ≤ 3 | 0.91 | <100 | 71% and 91% | Buhlmann Quantum Blue Calprotectin High Range Immunoassay |
Langhorst et al. [53] | 72/179 colonoscopies in 91patients | RI ≤ 1 | 0.7 | 13.9 | 11% and 99% | IDK® Calprotectin ELISA |
Lin et al. [54] | na/52 | UCEIS < 3 | 0.97 | 918 | 88% and 75% | ELISA, Quantum Blue Calprotectin High Range Rapid Test |
Lobatón et al. [55] | 35/146 colonoscopies in 123 patients | MES = 0 | 0.921 0.862 | 160 | 67% and 85%1 65% and 84%2 | 1Bühlmann ELISA 2QPOCT- Quantum Blue |
Nancey et al. [56] | 20/55 | RI ≤ 2 | 0.96 | 250 | 87% and 91% | ELISA, Bühlmann |
Önal et al. [57] | 30/60 | RI < 4 | 0.81 | 99.5 mg/L | 77% and 79% | ELISA Phi Cal |
Schoepfer et al. [58] | 54/228 | mBS ≤ 1 | 0.94 | 57 | 90% and 91% | ELISA Phi Cal |
Falvey et al. [59] | na/65 | mBS = 0 | 0.81 | 125 | 74% and 80% | ELISA CalPro |
Kristensen et al. [60] | 18/62 | MES = 0 | 0.88 | 61 | 84% and 83% | Calpro ELISA |
Kristensen et al. [60] | 18/62 | MES = 0 | 0.93 | 96 | 91% and 83% | ELISA, Bühlmann |
Scaioli et al. [61] | 45/121 | MES = 0 | 0.98 | 110 | 98% and 90% | ELISA, Calprest |
Takashima et al. [62] | 77/105 colonoscopies in 92 patients | MES ≤ 1 | 0.82 | 200 | 77% and 72% | ELISA PhiCal |
Theede et al. [63] | na/120 | MES = 01 UCEIS = 02 | 0.88 | 192 | 75% and 88%1 79% and 87%2 | ELISA, Bülhmann |
Voiosu et al. [64] | 16/48 (mixed UC and CD) | MES = 0 SES-CD ≤ 3 | 0.77 | 30 | 94% and 50% | Buhlmann Quantum Blue Reader® |
Yamaguchi et al. [65] | 94/105 (CR) | MES = 01 MES ≤ 12 | 0.641 0.872 | 1941 2002 | 71% and 53%1 67% and 91%2 | EliA Calprotectin 2, Thermo Fisher Scientific |
Nakov et al. [66] | 50/116 | UCEIS = 0 and MES = 0 | 0.988 | 99 | 97% and 98% | Quantum Blue® Calprotectin, Bühlmann Laboratories AG |
Hart et al. [67] | 159/185 | MES ≤ 1 | 0.722 | 170 | 65% and 69% | ELISA, Buhlmann |
Karling et al. [68] | 34/88 | MES = 0 | 0.707 | 63 | 67% and 68% | CALPRO, Calprotectin ELISA Test |
Yang Woon et al. [69] | 7/29 | MES = 0 | 0.88 | 201 | 82% and 100% | ELISA, Bühlmann Laboratories AG |
Ryu et al. [70] | 51/174 | MES = 0 | 0.863 | 170 | 78.4% and 74.8% | ELISA, Thermo Fisher Scientific |
Ryu et al. [70] | 59/174 | UCEIS ≤ 1 | 0.847 | 170 | 74.6% and 76.5% | ELISA, Thermo Fisher Scientific |
Authors | N MH/Total | MH Definition | Marker Performance | Assay * | ||
---|---|---|---|---|---|---|
AUC | Cutoff (µg/g) | Sens. and Spec. | Type, Manufacturer | |||
Iwamoto et al. [71] | 39/69 | eSES-CD = 0 | 0.91 | 92 | 94% and 88% | EliA, Calprotectin 2 |
Lopes et al. [72] | 19/29 | SES-CD = 0 | 0.88 | 100 | 92% and 65% | EliA, Calprotectin |
Chen et al. [47] | 56/92 | SES-CD | 0.91 | 250 | 93% and 70% | ELISA, Bühlmann Calprotectin |
Vazquez-Maron et al. [73] | 22/71 | SES-CD ≤ 2 | na | 71 | 96% and 52% | ELISA, Calprest® |
Arai et al. [74] | 123 colonoscopies in 89 patients | SES-CD = 0 | 0.81 | 215 | 83% and 71% | ELISA, PhiCal Calprotectin |
Inokuchi et al. [75] | 23/71 | SES-CD = 0 | 0.82 | 180 | 87% and 71% | ELISA, Phical Calprotectin |
Jusué et al. [32] | 24/52 | SES-CD = 0 | 0.71 0.72 | 541 1222 | 63% and 71%1 75% and 71%2 | Rapid Kit, Quantum Blue® Bühlmann 1low-range test; 2high-range test |
Lin et al. [54] | na/36 | CDEIS < 6 | 0.74 | 918 | 50% and 100% | ELISA, Quantum Blue Calprotectin High Range Rapid Test |
Lobatón et al. [76] | 40/115 | CDEIS ≤ 3 | 0.941 0.932 | 2741 2722 | 76% and 97% | 1Bühlmann ELISA, 2QPOCT-Quantum Blue |
Nancey et al. [56] | 40/78 | SES-CD ≤ 2 | 0.77 | 250 | 78% and 71% | ELISA, Bühlmann |
Schaffer et al. [77] | 51/136 | SES-CD ≤ 3 | 0.83 | 250 | 76% and 75% | ELISA assay RIDASCREEN® CALPROTECTIN, R-Biopharm AG |
Falvey et al. [59] | na/108 | SES-CD ≤ 2 | 0.74 | 125 | 71% and 71% | ELISA CalPro |
Karczewski et al. [78] | 5/55 | CDEIS < 3 | na | 76 | 96% and 80% | CalproLabTM ELISA kit |
Björkesten et al. [26] | 23/126 colonoscopies in 64 patients | SES-CD ≤ 2 | 0.85 | 100 | 84% and 74% | ELISA, PhiCal |
Marker | N MH/Total | MH Definition | ↑/↓ in Active Disease | Correlation with Endoscopic Score | Marker Performance | Authors | ||
---|---|---|---|---|---|---|---|---|
AUC | Cutoff | Sens. and Spec. | ||||||
MMP-9 | na/47 | MES < 1 | ↑ | r = 0.653, p < 0.002 | 0.9 | 2.38 ng/mL | 97% and 83% | Annahazi et al. [91] |
MMP-9 | 9/32 | MES ≤ 1 | ↑ | r = 0.58, p < 0.001 | 0.87 | 900 ng/g | 80% and 91% | Buisson et al. [92] |
MMP-9 | na/54 | MES ≤ 1 | ↑ | r = 0.381, p = 0.021 | 0.81 | 0.20 ng/mL | 75% and 96% | Farkas et al. [93] |
Lactoferrin | 72/179 colonoscopies in 91patients | RI ≤ 1 | ↑ | r = 0.4, p < 0.001 | 0.73 | 11.9 μg/g | 75% and 63% | Langhorst et al. [53] |
Lactoferrin | 18/60 | UCEIS = 0 | ↑ | r = 0.56, p < 0.0001 | 0.71 | 78.3 ng/mL | 57% and 88% | Mine et al. [45] |
Lactoferrin | na/20 | MES = 0 | ↑ | r = 0.792, p < 0.01 | 0.88 | 288.8 ng/mL | 69% and 100% | Sagawa et al. [94] |
Lipocalin-2 | 9/32 | MES ≤ 1 | ↑ | ns | 0.68 | 6700 ng/g | 80% and 82% | Buisson et al. [92] |
Lipocalin-2 | 265/370 | MES = 0 | ↑ | na | 0.65 | 7 μg/g1 10 μg/g2 | 40% and 77%1 62% and 62%2 | Magro et al. [95] |
Lipocalin-2 | UC: 15/431 | MES ≤ 11 | ↑ | r = 0.82, p < 0.011 | 0.86 | 2.2 mg/kg | 78% and 87% | Thorsvik et al. [96] |
CD: 7/302 | SES-CD ≤ 22 | r = 0.58, p < 0.012 | ||||||
Neopterin | 20/55 | RI ≤ 2 | ↑ | r = 0.72, p < 0.001 | 0.98 | 200 pmol/g | 100% and 74% | Nancey et al. [56] |
F-HNP | 26/45 | MES ≤ 1 | ↑ | r = 0.659, p < 0.001 | 0.86 | 32 ng/mL | 96% and 74% | Kanmura et al. [97] |
PMNE | 72/179 colonoscopies in 91 patients | RI ≤ 1 | ↑ | r = 0.38, p < 0.001 | 0.7 | 0.035 μg/mL | 39% and 87% | Langhorst et al. [53] |
Marker | N MH/Total | MH Definition | ↑/↓ in Active Disease | Correlation with Endoscopic Score | Marker Performance | Authors | ||
---|---|---|---|---|---|---|---|---|
AUC | Cutoff | Sens. and Spec. | ||||||
MMP-9 | 31/54 | CDEIS no ulceration | ↑ | r = 0.55, p < 0.001 | 0.72 | 350 ng/g | 64% and 90% | Buisson et al. [92] |
MMP-9 | na/50 | SES-CD ≤ 4 | ↑ | na | ns | Farkas et al. [93] | ||
Lactoferrin | na/101 | SES-CD ≤ 3 | ↑ | r = 0.5, p < 0.0001 | 0.68 | 145.82 μg/mL | 85% and 61% | Klimczak et al. [98] |
Lipocalin-2 | 31/54 | CDEIS no ulceration | ↑ | r = 0.49, p < 0.001 | 0.68 | 67000 ng/g | 46% and 86% | Buisson et al. [92] |
Neopterin | 40/78 | SES-CD ≤ 2 | ↑ | r = 0.47, p < 0.001 | 0.75 | 200 pmol/g | 73% and 74% | Nancy et al. [56] |
N MH/Total | MH Definition | Correlation with Endoscopic Score | Marker Performance | Authors | ||
---|---|---|---|---|---|---|
AUC | Cutoff | Sens. and Spec. | ||||
47/791 66/792 | MES = 01 MES ≤ 12 | r = 0.61, p < 0.05 | 0.771 0.962 | 0.05 mg/dL1 0.39 mg/dL2 | 71% and 71%1 92% and 92%2 | Arai et al. [74] |
20/43 | EAI ≤ 3 | na | 0.80 | 3.8 mg/L | 90% and 67% | Beyazit et al. [99] |
6/34 | MES = 0 | r = 0.35, p = 0.07 | na | 5 mg/L | 65% and 50% | Bodelier et al. [81] |
12/19 (CR)1 12/45 (all)2 | MES ≤ 2 | r = 0.634, p < 0.001 | 0.861 0.812 | 5 mg/L | 100% and 23%1 100% and 42%2 | Chen et al. [47] |
28/66 (NT)1 88/132 (T)2 pooled3 | MES ≤ 1 | r = 0.317, p < 0.011 r = 0.408, p < 0.012 r = 0.372, p < 0.013 | 0.701 0.802 0.773 | 5 mg/L1 7.2 mg/L2 7.3 mg/L3 | na and 82%1 44% and 93%2 39% and 91%3 | de Bruyn et al. [100] |
48/103 | MES ≤ 1 | r = 0.326, p = 0.001 | 0.60 | 0.7 mg/L | 52% and 69% | Dranga et al. [101] |
29/44 | MES ≤ 1 | na | 0.77 | 28 mg/L | 71% and 85% | Hassan et al. [102] |
10/85 | MES = 0 | r = 0.386, p < 0.001 | na | 0.5 mg/dL | 33% and 100% | Jung et al. [103] |
30/48 | MES = 0 | ns | 0.7 | 0.25 mg/dL | 81% and 53% | Jusué et al. [32] |
72/179 colonoscopies in 91 patients | RI ≤ 1 | r = 0.29, p < 0.001 | 0.65 | 0.25 mg/dL | 46% and 82% | Langhorst et al. [53] |
16/53 | MES = 0 | r = 0.46, p < 0.001 | 0.673 | 0.5 mg/L | 54% and 83% | Neubauer et al. [104] |
82/149 | MES = 01 MES ≤ 12 | na | 0.621 0.762 | 1.6 mg/L1 2.2 mg/L2 | 58% and 66%1 65% and 82%2 | Rosenberg et al. [105] |
7/32 | MES ≤ 1 | r = 0.387, p < 0.05 | 0.77 | na | na | Samant et al. [106] |
34/134 | RI ≤ 3 | r = 0.503, p < 0.001 | na | 5 mg/L | 67% and 60% | Schoepfer et al. [30] |
54/228 | mBS ≤ 1 | r = 0.556, p < 0.001 | 0.78 | 6 mg/L | 72% and 68% | Schoepfer et al. [58] |
16/1291 50/1292 | Matts’ = 11 Matts’ ≤ 22 | na | 0.671 0.812 | na | na | Shinzaki et al. [107] |
9/34 (na)* | MES = 0 | na | 0.71 | 0.4 mg/L | 71% and 30% | Tran et al. [108] |
52/207 | mMES ≤ 11 cMES ≤ 82 | r = 0.38, p < 0.051 r = 0.52, p < 0.052 | 0.751 0.902 | 0.23 mg/dL | 81% and 57%1 81% and 85%2 | Uchihara et al. [109] |
94/105 (CR) | MES = 01 MES ≤ 12 | na | 0.621 0.742 | 0.08 mg/dL1 0.04 mg/dL2 | na 68% and 70%2 | Yamaguchi et al. [65] |
na/65 | mBS = 0 | r = 0.45, p < 0.001 | 0.68 | 5 mg/L | 80% and 50% | Falvey et al. [59] |
722 endoscopies in 552 patients | P-T = 01 MES ≤ 12 mBS = 03 HSI ≤ 44 RI ≤ 45 | r = 0.457, p < 0.0011 r = 0.503, p < 0.0012 r = 0.520, p < 0.0013 r = 0.507, p < 0.0014 r = 0.523, p < 0.0015 | 0.761 0.772 0.783 0.774 0.765 | 8 mg/L | 51% and 85%1 53% and 84%2 52% and 87%3 51% and 85%4 51% and 87%5 | Yoon et al. [110] |
N MH/Total | MH Definition | Correlation with Endoscopic Score | Marker Performance | Authors | ||
---|---|---|---|---|---|---|
AUC | Cutoff | Sens. and Spec. | ||||
42/209 endoscopies | SES-CD ≤ 2 | r = 0.56, p < 0.001 | 0.64 | 3 mg/L | 50% and 24% | Björkesten et al. [26] |
31/50 | SES-CD ≤ 3 | r = 0.45, p = 0.07 | na | 5 mg/L | 65% and 56% | Bodelier et al. [81] |
20/34 (CR)1 21/56 (all)2 | SES-CD ≤ 3 | r = 0.658, p < 0.01 | 0.761 0.812 | 5 mg/L | 83% and 46%1 91% and 71%2 | Chen et al. [47] |
38/108 | Descriptive corresponding with SES-CD ≤ 2 | r= 0.307, p < 0.001 | 0.74 | 5 mg/L | 79% and 57% | de Bruyn et al. [111] |
na/107 | SES-CD ≤ 2 | r = 0.44, p < 0.001 | 0.64 | 5 mg/L | 67% and 60% | Falvey et al. [59] |
na/33 | SES-CD = 0 | r = 0.709, p < 0.001 | 0.92 | 0.03 mg/dL | 86% and 89% | Hosomi et al. [112] |
19/55 | SES-CD ≤ 3 | r = 0.61, p < 0.01 | 0.75 | 0.11 mg/dL | 68% and 78% | Ishihara et al. [113] |
6/34 | SES-CD ≤ 3 | r = 0.585, p < 0.001 | na | 0.4 mg/dL | 89% and 67% | Jung et al. [104] |
4/55 | CDEIS ≤ 2 | r = 0.672, p < 0.001 | na | 3 mg/L | 80% and 76% | Karczewski et al. [78] |
11/43 | Descriptive corresponding with SES-CD ≤ 3 | na | 0.78 | 1.1 mg/L | 100% and 38% | Miranda-García et al. [114] |
51/136 | SES-CD ≤ 3 | r = 0.458, p < 0.001 | 0.69 | 5 mg/L | 84% and 53% | Schaffer et al. [77] |
26/140 | SES-CD ≤ 3 | r = 0.53, p < 0.01 | na | 5 mg/L | 58% and 68% | Schoepfer et al. [30] |
39/94 | Descriptive corresponding with SES-CD ≤ 2 | na | 0.75 | 4 mg/L | 69% and 62% | Yarur et al. [115] |
Marker | N MH/Total | MH Definition | ↑/↓ in Active Disease | Correlation with Endoscopic Score | Marker Performance | Authors | ||
---|---|---|---|---|---|---|---|---|
AUC | Cutoff | Sens. and Spec. | ||||||
VEGF-A | 16/37 | MES = 0 | ↑ | r = 0.397, p = 0.015 | 0.72 | 341 ng/mL | 64% and 85% | Algaba et al. [126] |
ADA | 20/43 | EAI ≤ 3 | ↑ | na | 0.87 | 9.45 U/L | 84% and 83% | Beyazit et al. [99] |
ST2 | 25/83 | EAI ≤ 4 | ↑ | na | 0.81 | 47.1 pg/mL | 72% and 72% | Boga et al. [127] |
ST2 | 44/84 | MES ≤ 1 | ↑ | r = 0.762, p < 0.001 | 0.92 | 74.87 ng/L | 83% and 83% | Díaz-Jiménez et al. [128] |
ST2 | 18/24 | MES ≤ 1 | ↑ | r = 0.66, p < 0.001 | na | 74.87 ng/L | 44% and 95% | Díaz-Jiménez et al. [129] |
NGAL | 14/41 | MES ≤ 1 | ↑ | r = 0.574, p < 0.05 | 0.76 | 43.6 ng/mL | 96% and 54% | Budzynska et al. [130] |
NGAL-MMP9 complex | 28/66 (NT)1 88/132 (T)2 pooled3 | MES ≤ 1 | ↑ | r = 0.317, p < 0.011 r = 0.382, p < 0.012 r = 0.37, p < 0.013 | 0.751 0.782 0.783 | 97.7 ng/mL1 93.2 ng/mL2 97.7 ng/mL3 | 43% and 93%1 44% and 91%2 43% and 91%3 | de Bruyn et al. [100] |
sIL2R | na/68 | MES = 0 | ↑ | r = 0.357, p = 0.003 | 0.65 | 274 U/mL | 60% and 76% | Hosomi et al. [112] |
sTREM-1 | 10/85 | MES = 0 | ↑ | r = 0.498, p < 0.001 | na | 60 pg/mL | 59% and 80% | Jung et al. [103] |
IL-6 | 5/45 | MES = 0 | ↑ | r = 0.596, p < 0.001 | 0.93 | 9.6 pg/mL | 80% and 95% | Mankowska-Wierzbicka et al. [116] |
IL-17 | 5/45 | MES = 0 | ↑ | r = 0.578, p < 0.001 | 0.93 | 6.6 pg/mL | 60% and 92% | Mankowska-Wierzbicka et al. [116] |
TNFα | 5/45 | MES = 0 | ↑ | r = 0.701, p < 0.001 | 0.98 | 7.6 pg/mL | 80% and 95% | Mankowska-Wierzbicka et al. [116] |
IL-9 | na/53 | MES = 0 | ↑ | r = 0.74, p < 0.001 | 0.97 | 20.5 pg/mL | 94% and 92% | Matusiewicz et al. [119] |
GM-CSF | 16/53 | MES = 0 | ↑ | r = 0.56, p < 0.001 | 0.91 | 16.7 pg/mL | 69% and 97% | Neubauer et al. [104] |
IFNγ | 16/53 | MES = 0 | ↑ | r = 0.55, p < 0.001 | 0.78 | 83.2 pg/mL | 100% and 60% | Neubauer et al. [104] |
IL-12(p70) | 16/53 | MES = 0 | ↑ | r = 0.49, p < 0.001 | 0.71 | 21.6 pg/mL | 50% and 100% | Neubauer et al. [104] |
Nampt | 66/98 | MES ≤ 1 | ↑ | r = 0.47, p < 0.001 | 0.77 | 1.54 ng/mL | 76% and 75% | Neubauer et al. [131] |
IL-8 | 22/67 | BS ≤ 1 (inactive + mild) | ↑ | na | na | 13.74 pg/mL | 69% and 55% | Rodriguez-Peralvarez et al. [132] |
LRG | 16/1291 50/1292 | Matts’ = 11 Matts’ ≤ 22 | ↑ | na | 0.761 0.852 | na | na | Shinzaki et al. [107] |
TTF3 | 43/76 (CR) | BS ≤ 1 | ↑ | na | 0.73 | 1.27 ng/mL | 70% and 68% | Srivastava et al. [133] |
TTF3 | 50/116 | UCEIS = 0 and MES = 0 | ↑ | r = 0.82 for UCEIS, r = 0.811 for EMS, p < 0.001 | 0.927 | 6.74 ng/mL | 89.9% and 86.9% | Nakov et al. [66] |
LL-37 | 9/34 (na)* | MES = 0 | ↓ | na | 0.76 | 32 mg/mL | 100% and 38% | Tran et al. [108] |
Leptin | 8/23 UC1 5/11 CD2 | MES = 01 SES-CD = 02 | ↓ | na | 0.65 | 2.5 ng/mL | 88% and 45% | Trejo-Vasquez et al. [134] |
ALB | 52/207 | mMES ≤ 11 cMES ≤ 82 | ↓ | r = −0.52, p < 0.051 r = −0.65, p < 0.052 | 0.771 0.902 | 4.2 g/dL | 73% and 72%1 79% and 88%2 | Uchihara et al. [109] |
ALB | 94/105 (CR) | MES = 01 MES ≤ 12 | ↓ | na | 0.501 0.552 | 4.3 g/dL | na 34% and 90% | Yamaguchi et al. [65] |
Marker | N MH/Total | MH Definition | ↑/↓ in Active Disease | Correlation with Endoscopic Score | Marker Performance | Authors | ||
---|---|---|---|---|---|---|---|---|
AUC | Cutoff | Sens. and Spec. | ||||||
Ang1 | 19/35 | SES-CD ≤ 2 | ↑ | r = 0.362, p = 0.049 | 0.65 | 47.8 ng/mL | 52% and 67% | Algaba et al. [126] |
ST2 | 52/8 | SES-CD ≤ 2 | ↑ | na | 0.73 | 57.6 pg/mL | 100% and 56% | Boga et al. [127] |
NGAL | 45/79 | SES-CD ≤ 7 (inactive + mild) | ↑ | ns | 0.61 | 72.5 ng/mL | 48% and 83% | Budzynska et al. [130] |
NGAL-MMP9 complex | 38/108 | Descriptive corresponding with SES-CD ≤ 2 | ↑ | r= 0.296, p < 0.001 | 0.77 | 45 ng/mL | 82% and 60% | de Bruyn et al. [111] |
IL-9 | 23/50 | Descriptive corresponding with CDEIS ≤ 2 | ↑ | r = 0.395, p < 0.001 | 0.78 | 18.1 pg/mL | 52% and 100% | Feng et al. [138] |
sIL2R | na/33 | SES-CD = 0 | ↑ | r = 0.516, p = 0.002 | 0.74 | 283 U/mL | 71% and 73% | Hosomi et al. [112] |
sCD14-ST | na/33 | SES-CD = 0 | ↑ | r = 0.512, p = 0.002 | 0.85 | 89 pg/mL | 86% and 85% | Hosomi et al. [112] |
SAA | 19/55 | SES-CD ≤ 3 | ↑ | r = 0.64, p < 0.01 | 0.77 | 5.9 μg/dL (mL)* | 68% and 83% | Ishihara et al. [113] |
SAA | 39/94 | Descriptive corresponding with SES-CD ≤ 2 | ↑ | na | 0.77 | 28 mg/L | 95% and 64% | Yarur et al. [115] |
sTREM-1 | 6/34 | SES-CD ≤ 3 | ↑ | ns | Na | 60 pg/mL | 29% and 83% | Jung et al. [103] |
IL-17 | 4/55 | CDEIS ≤ 2 | ↑ | r = 0.296, p < 0.005 | Na | 7.05 pg/mL | 80% and 74% | Karczewski et al. [78] |
ERβ/ERα | 11/31 | SES-CD ≤ 2 | na | 0.84 | 0.85 (ratio) | 91% and 70% | Linares et al. [139] | |
IL-6 | 6/32 | CDEIS ≤ 7 | ↑ | r = 0.957, p < 0.001 | 1.00 | 15.9 pg/mL | 100% and 100% | Ljuca et al. [137] |
Orosomucoid | 11/43 | Descriptive corresponding with SES-CD ≤ 3 | ↑ | na | 0.85 | 119.5 mg/dL | 100% and 57% | Miranda-García et al. [114] |
Fibrinogen | 11/43 | Descriptive corresponding with SES-CD ≤ 3 | ↑ | na | 0.81 | 457 mg/dL | 100% and 65% | Miranda-García et al. [114] |
Ficolin-2 | 51/136 | SES-CD ≤ 3 | ↑ | r = 0.171, p = 0.047 | 0.61 | 2.404 μg/mL | 51% and 68% | Schaffer et al. [87] |
IL-1β | 25/47 (RP) | Descriptive corresponding with SES-CD ≤ 2 | ↑ | na | 0.88 | na | na | Yarur et al. [140] |
ICAM | 25/47 (RP) | Descriptive corresponding with SES-CD ≤ 2 | ↑ | na | 0.89 | na | na | Yarur et al. [140] |
Marker | N MH/Total | MH Definition | ↑/↓ in Active Disease | Correlation with Endoscopic Score | Marker Performance | Authors | ||
---|---|---|---|---|---|---|---|---|
AUC | Cutoff | Sens. and Spec. | ||||||
PGE | 47/791 66/792 | MES = 01 MES ≤ 12 | ↑ | r = 0.85, p < 0.05 | 0.901 0.982 | 21.8 μg/g CR1 34.7 μg/g CR2 | 81% and 81%1 89% and 89%2 | Arai et al. [142] |
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Krzystek-Korpacka, M.; Kempiński, R.; Bromke, M.; Neubauer, K. Biochemical Biomarkers of Mucosal Healing for Inflammatory Bowel Disease in Adults. Diagnostics 2020, 10, 367. https://doi.org/10.3390/diagnostics10060367
Krzystek-Korpacka M, Kempiński R, Bromke M, Neubauer K. Biochemical Biomarkers of Mucosal Healing for Inflammatory Bowel Disease in Adults. Diagnostics. 2020; 10(6):367. https://doi.org/10.3390/diagnostics10060367
Chicago/Turabian StyleKrzystek-Korpacka, Małgorzata, Radosław Kempiński, Mariusz Bromke, and Katarzyna Neubauer. 2020. "Biochemical Biomarkers of Mucosal Healing for Inflammatory Bowel Disease in Adults" Diagnostics 10, no. 6: 367. https://doi.org/10.3390/diagnostics10060367