Table 2.
Summary of anaphylaxis mediators, cell source, testing characteristics, and evidence of their potential use as biomarkers in anaphylaxis (1–7, 9–22, 24, 27–40, 42–90)
| Mediator | Source | Recommended sampling time | Methods available for routine assessment | Correlation with severe anaphylaxis | Half-life |
|---|---|---|---|---|---|
| Preformed | |||||
| Histamine (plasma, urine) | MC, BS NT | 0–30 min | Yes | Yes | < 15 min |
| Histamine (24-h urine) | MC, BS, NT | 0–24 h | Yes | Yes | UNK (0–24 h) |
| N-m-histamine (plasma, 24-h urine) | MC, BS, NT | 0–24 h | Yes | Yes | UNK (0–24 h) |
| N-m-imidazole acetic acid (24-h urine) | MC, BS, NT | 0–24 h | Yes | UNK | UNK (0–24 h) |
| Tryptase (serum/plasma) | MC, BS | 15 min–3 h | Yes | Yes | ~ 2 h |
| Chymase (serum) | MC, BS | 0–24 h | No | Yes | > 24 h |
| Carboxypeptidase A3 (serum/plasma) | MC, BS | 0–8 h | No | UNK | > tryptase (2–8 h) |
| Basogranulin (serum) | BS | UNK | No | No | UNK |
| Heparin (plasma) | MC, BS | UNK | No | Yes | UNK |
| DPPI/cathepsin C (serum) | MC, BS | UNK | No | UNK | UNK (similar to histamine) |
| Cathepsin G (serum) | MC, BS, EOS, NT | UNK | No | UNK | UNK |
| Newly generated over minutes | |||||
| Bradykinin (plasma) | Plasma | UNK | No | Yes | < 1 min |
| FXII, PK, HK, thrombin (plasma) | Plasma | UNK | FXII, thrombin | UNK | UNK |
| LTE4 (24-h urine, plasma) | MC, BS, EOS, NT, MAC | 0–24 h | No | Yes | 7 min |
| LTB4, LTC4, LTD4 (24-h urine) | MC, BS, NT | 0–24 h | No | UNK | < 7 min |
| PGD2 (serum) | MC, EOS, NT, MN, PT | 0–24 h | No | Yes | 30 min |
| 9α,11β-PGF2 (serum) | MC, PT | UNK (5–15 min) | No | UNK | UNK |
| 2,3-dinor-11β-PGF2α (24-h urine) | MC, PT | UNK (0–24 h) | No | UNK | UNK |
| TXA2 (serum/plasma, urine) | MC, EOS, PT | UNK | No | UNK | 30 s |
| TXB2 (serum/plasma, urine) | MC | UNK | No | UNK | 60 min |
| PAF* (plasma) | MC, BS, EOS, NT, MAC, MN, PT, EC | UNK | No | Yes | < 5 min |
| PAF-AH (serum) | MC, MAC, PT plasma | UNK | No | Yes | 30 min |
| Nitric oxide | EC | UNK | No | UNK | UNK |
| C3a, C5a (plasma) | Plasma | UNK | No | No | UNK |
| TNF-α* (serum/plasma) | MC, MAS, NT, MAC | UNK | Yes | UNK | 30 min |
| Newly generated over hours | |||||
| Stem cell factor (serum/plasma) | MC | UNK | No | Yes** | UNK |
| TGF-β (serum/plasma) | MC, EOS | UNK | Yes | UNK, potential** |
2–3 min active 90 min latent** |
| CXCL4/PF4, PDGF | PT | UNK | No | UNK | < 3 min |
| IL-1b (serum/plasma) | MC, NT | 0–15 min | No | UNK | 19 min** |
| IL-2, IL-22 (serum/plasma) | MC | 0–10 h | No | IL-2 yes | UNK |
| IL-4/IL-13 (serum/plasma) | MC, BS, EOS | UNK (0–24 h) | No | IL-4 yes** | 35–90 min |
| IL-10 (serum/plasma) | MC, EOS | UNK (0–24 h) | Yes | Yes | 1–3.5 h |
| IL-6 (serum/plasma) | MC, BS, NT, MAC | UNK (0–24 h) | Yes | Yes | 2–6 h |
| IL-8 (serum/plasma) | MC, EOS, NT | UNK (< 3 h) | No | No | < 4 h |
| CCL2/MCP-1 (serum/plasma) | MC, NT, MAC, MN, EC | UNK (0–30 min) | No | UNK, potential | 30 min |
| CCL5/RANTES (serum/plasma) | MC, EOS, MN | UNK | No | UNK | 14–18 h |
| MPO (serum/plasma) | NT, MN | UNK (< 5 h) | No | Yes | UNK 4–5 h** |
| Other possible biomarkers (source cells) | Chondroitin sulfate (MC, BS), elastase* (NT), TSLP (MC, EC, SMC), IL-31 (MC, BS, EOS, MAC, LT), IL-33 (MC, BS), IL-3/IL-5/IL-16/IL-18 (MC, EOS), IL-17 (NT), IL-23/IL-27/FGF (MAC), G-CSF (MC, NT, MAC, MN, EC), GM-CSF (MC, BS, EC), M-CSF (MC, MN, EC), VEGF (MC, MAC, PT), S1P (MC, PT, EC, ERY), IFN- γ (NT, LT, NK), endothelin-1 (MC, MAC, MN, EC, SMC), prostacyclin (MC, PT, EC, SMC), plasminogen activator (MC), MBP (EOS) | ||||
MC, mast cell; BS, basophil; NT, neutrophil; PT, platelet; EOS, eosinophil; MAC, macrophage; MN, monocyte; EC, endothelial cell; SMC, smooth muscle cell; ERY, erythrocyte; LT, T lymphocyte; NK, natural killer cell; N-m, N-methyl; DPPI, dipeptidyl peptidase I; FXII, coagulation factor XII; PK, prekallikrein; HK, high molecular weight kininogen; PAF, plasmin activator factor; PAF-AH, acetylhydrolase; LTE4, E4 leukotriene; LTB4, B4 leukotriene; LTC4, C4 leukotriene; LTD4, D4 leukotriene; PGD2, D2 prostaglandin; TXA2, A2 thromboxane; TXB2, B2 thromboxane; TGF-β, tumor grow factor beta; TNF-α, tumor necrosis factor alpha; CXCL4/PF4, platelet factor 4; PDGF, platelet-derived growth factor; TSLP, thymic stromal lymphopoietin; FGF, fibroblast grow factor; G-CSFR, granulocyte colony stimulating factor receptor; GM-CSFR, granulocyte–macrophage colony-stimulating factor receptor; M-CSF, VEGF CCL2/MCP-1 CCL5/RANTES S1P; MPO, myeloperoxidase; MBP, major basic protein; IFN-γ, interferon gamma
*Also preformed, but mainly newly generated
**Studies performed in mammals, not in humans