Table 2.
Candidate biomarkers of joint damage in rheumatoid arthritis and psoriatic arthritis
| Candidate biomarker | Evidence for role in inflammatory arthritis | Use |
|---|---|---|
| Inflammatory proteins | ||
| C-reactive protein | Opsonisation and compliment activation | RA |
| Calprotectin (S100A12) | Ca2+ binding protein released upon phagocyte activation, important intracellular and extracellular roles | RA/PsA |
| Calgranulin (S100A8/S100A9) | Ca2+ binding protein with pleotropic effects. Regulates myeloid derived cells | PsA |
| A-SAA | Promotes the production of MMPs | RA/PsA |
| Cytokines | ||
| IL-1 | Promotes activation of keratocytes, endothelial cells, chondrocytes and osteoclasts. Promotes the production of proinflammatory cytokines | PsA |
| IL-6 | Promotes neutrophil chemotaxis and production of proinflammatory cytokines, induces an acute phase response | RA |
| IL-13 | Promotes antibody production by B cells | RA |
| IL-15 | Induces T cell proliferation and B cell differentiation. Recruits memory T cells to the synovium and induces TNFα production | PsA |
| IL-16 | Promotes chemotaxis of CD4+ T cells, monocytes and eosinophils. Modulates T-cell activation | RA |
| IL-22 | Induces proliferation of fibroblasts and production of MCP-1 (monocyte chemokine) | RA |
| IL-33 | Promotes chronic inflammatory response | RA |
| Chemokines | ||
| CCL3 | Lymphocyte, monocyte, basophil, eosinophil chemoattractant | PsA |
| CCL11 | Eosinophil chemoattractant | PsA |
| CXCL13 | B-cell chemoattractant | RA |
| Adipokines | ||
| Adiponectin | Induces IL-6 and MMP-1 production by SLFs. Promotes IL-6, TNFα and MCP-1 production in chondrocytes | RA |
| Visfatin | Role unclear, thought to modulate inflammation | RA |
| Markers of angiogenesis | ||
| VEGF | Potent inducer of angiogenesis and vascular permeability | RA/PsA |
| Angiopotietin-1 | Promotes angiogenesis (growth of new blood vessels) | RA |
| Angiopotietin-2 | Promotes angiogenesis | PsA |
| Auto-antibodies | ||
| Rheumatoid factor | Forms immune complexes, promotes complement activation and formation of rheumatoid nodules | RA |
| Anti-CCP | Promotes complement activation | RA |
| Anti-Carp | Bind homocitrulline containing proteins | RA |
| Enzyme mediators of destruction | ||
| MMP-1 | Degrades collagen | RA |
| MMP-3 | Degrades collagen | RA |
| Regulators of bone remodelling | ||
| RANKL | Induces osteoclast bone destruction | PsA |
| M-CSF | Induces aggressive phenotype in macrophages | PsA |
| Products of collagen degradation | ||
| COMP | Cartilage oligomatrix protein | RA |
| CTXI | C-terminal telopeptide of collagen type I | RA |
| CTXII | C-terminal telopeptide of collagen type I | RA |
| C1,2C | Collagen type II degradation product | RA |
| C2C | Collagen type II degradation product | RA |
Candidate biomarkers predictive of joint damage in RA and PsA have been identified in the literature. These include inflammatory proteins, cytokines, chemokines, adipokines, markers of angiogenesis, auto-antibodies, enzyme mediators of destruction, molecules that regulate bone turnover and products of collagen degradation. For references see text. A-SAA acute-phase serum amyloid A; anti-Carp, anti-carbamylated protein antibodies; CCL, chemokine ligand; CCP, cyclic citrullinated peptide; CXCL, chemokine (C-X-C) motif ligand; IL, interleukin; M-CSF, macrophage colony stimulating factor; MCP-1, monocyte chemoattractant protein-1; MMP, matrix metalloproteinase; RA, rheumatoid arthritis; PsA, psoriatic arthritis; RANKL, receptor activator of nuclear factor-κB ligand; SLF, synovium-like fibroblasts; TNFα, tumour necrosis factor alpha; VEGF, vascular endothelial growth factor