Table 2.
Best evidence synthesis of laboratory markers
| Category | Marker | Good/fair quality studies | Poor quality studies | Evidence |
|---|---|---|---|---|
| ACPA | Anti-CCP |
3x positive association [37–39] 1x not associated [40] |
Moderate evidence of positive association | |
| Anti-MCV | 1x positive association [41] | Limited evidence of positive association | ||
| Bone metabolism | 25(OH) vitamin D | 2x no association [42, 43] | 3x no association [44–46] | Strong evidence of no association |
| Alkalic phosphate | 1x no association [43] | 2x no association [47, 48] | Moderate evidence of no association | |
| Calcium | 2x no association [47, 48] | Moderate evidence of no association | ||
| COMP | 1x no association [49] | 1x no association [50] | Moderate evidence of no association | |
| CPII:C2C | 1x positive association [49] | Moderate evidence of positive association | ||
| CTX | 2x no association [47, 51] | Moderate evidence of no association | ||
| DKK-1 | 1x no association [52] | 1x positive association [53] | Conflicting evidence | |
| MMP3 | 3x positive association [49, 52, 54] | 1x no association [51] | Strong evidence of positive association | |
| OPG | 2x positive association [49, 52] | 4x no association [50, 51, 53, 55] | Strong evidence of positive association | |
| OPG/RANKL ratio | 2x negative association [50, 56] | Moderate evidence of negative association | ||
| Osteoclast precursors | 1x positive association [56] | Limited evidence of positive association | ||
| Phosphate | 1x no association [43] | 1x no association [47] | Moderate evidence of no association | |
| RANKL | 1x no association [49] | Conflicting evidence | ||
| Urine Hp | 1x negative association [48] | Limited evidence of negative association | ||
| Cell culture | IL-2 secretion | 1x positive association [58] | Limited evidence of positive association | |
| IL-17 secretion |
1x positive association [59] 1x no association [58] |
Conflicting evidence | ||
| Cytokines | (Change in) CXCL10 |
1x positive association [27] 1x positive association [60] |
Strong evidence of positive association | |
| IL-6 |
1x positive association [61] 1x positive association [62] |
1x positive association [63] 1x no association [64] |
Strong evidence of positive association | |
| IL-12/23 p40 | 1x no association [49] | 1x positive association [56] | Conflicting evidence | |
| IL-23 | 1x positive association [65] | Limited evidence of positive association | ||
| IL-33 | 1x positive association [56] | Limited evidence of positive association | ||
| IL-34 | 1x positive association [66] | 1x positive association [56] | Moderate evidence of positive association | |
| IL-35 | 1x positive association [56] | Limited evidence of positive association | ||
| IL-36a | 1x negative association [56] | Limited evidence of negative association | ||
| IL-38 | 1x positive association [56] | Limited evidence of positive association | ||
| M-CSF | 1x negative association [52] | 1x positive association [53] | Conflicting evidence | |
| TNFα | 2x positive association [56, 64] | Moderate evidence of positive association | ||
| Cytologic phenotype | CD3+ CD71+ count | 1x positive association [58] | Limited evidence of positive association | |
| CD4 + CD45RA-CXCR3 + CCR4- | 1x negative association [67] | Limited evidence of negative association | ||
| CD4 + CD45RA-CXCR3 + CCR6- | 1x negative association [67] | Limited evidence of negative association | ||
| CD4 + CD45RA-IFNy+ | 1x negative association [67] | Limited evidence of negative association | ||
| CD4 + CD45RA-IL17+ | 1x positive association [67] | Limited evidence of positive association | ||
| CD4 + TEMCXCR3 + CCR4- | 1x negative association [67] | Limited evidence of negative association | ||
| CD4 + TEMIL17A+ | 1x negative association [67] | Limited evidence of negative association | ||
| CD8 + CD45RA-CCR6 + CXCR3-CD69+ | 1x positive association [67] | Limited evidence of positive association | ||
| CD8 + CD45RA-IL17+ | 1x positive association [67] | Limited evidence of positive association | ||
| CD8 + TCMCD69+ | 1x positive association [67] | Limited evidence of positive association | ||
| CD8 + TEMIL17A+ | 1x positive association [67] | Limited evidence of positive association | ||
| CD8 + TEMRACCR6 + CXCR3-CD69- | 1x positive association [67] | Limited evidence of positive association | ||
| CD8 + TEMRACXCR3 + CCR4- | 1x negative association [67] | Limited evidence of negative association | ||
| CD8 + TEMRACXCR3 + CCR6-CD69+ | 1x positive association [67] | Limited evidence of positive association | ||
| Mean platelet volume | 2x positive association [68, 69] | Moderate evidence of positive association | ||
| Monocyte count | 1x positive association [70] | Limited evidence of positive association | ||
| Neutrophil count | 1x positive association [70] | Limited evidence of positive association | ||
| Neutrophil to lymphocyte ratio | 1x positive association [70] | Limited evidence of positive association | ||
| Platelet count | 1x positive association [70]1x no association [68] | Conflicting evidence | ||
| Platelet to lymphocyte ratio | 1x positive association [70] | Limited evidence of positive association | ||
| White blood count |
1x positive association [70] 1x no association [46] |
Conflicting evidence | ||
| Inflammation marker | CRP |
5x positive association [43, 49, 54, 66, 71] 1x no association [27] |
Strong evidence of positive association | |
| ESR |
1x positive association [66] 1x no association [43] |
Conflicting evidence | ||
| Lipid metabolism | Adiponectin | 1x positive association [71] | 1x negative association [64] | Conflicting evidence |
| ApoA to ApoB ratio | 1x positive association [76] | Limited evidence of positive association | ||
| ApoB | 1x positive association [76] | Limited evidence of positive association | ||
| CER | 1x positive association [46] | Limited evidence of positive association | ||
| Glucose | 2x no association [42, 71] | 4x no association [46, 62, 76, 77] | Strong evidence of no association | |
| HDL | 2x no association [42, 71] | 3x no association [62, 72, 77] | Strong evidence of no association | |
| Insulin | 1x negative association [77] | Limited evidence of negative association | ||
| LDL | 2x no association [42, 71] |
1x positive association [62] |
Strong evidence of no association | |
| LDL:HDL ratio | 2x positive association [62, 76] | Moderate evidence of positive association | ||
| Leptin | 1x positive association [71] | 1x no association [64] | Conflicting evidence | |
| Total cholesterol |
1x negative association [42] 1x no association [71] |
1x positive association [62] |
Conflicting evidence | |
| Total cholesterol/HDL | 1x no association [42] | 1x positive association [76] | Conflicting evidence | |
| Triglycerides | 2x no association [42, 71] | Strong evidence of no association | ||
| VLDL | 2x no association [62, 76] | Moderate evidence of no association | ||
| miRNA expression | let-7b-3p | 1x negative association [78] | Moderate evidence of negative association | |
| let-7b-5p | 1x negative association [78] | Moderate evidence of negative association | ||
| let-7e-5p | 1x positive association [78] | Moderate evidence of positive association | ||
| miR-26a-5p | 1x positive association [78] | Moderate evidence of positive association | ||
| miR-27a-3p | 1x positive association [78] | Moderate evidence of positive association | ||
| miR-27b-3p | 1x positive association [78] | Moderate evidence of positive association | ||
| miR-29a-3p | 1x positive association [78] | Moderate evidence of positive association | ||
| miR-30e-5p | 1x positive association [78] | Moderate evidence of positive association | ||
| miR-92a-3p | 1x negative association [78] | Moderate evidence of negative association | ||
| miR-92b-3p | 1x negative association [78] | Moderate evidence of negative association | ||
| miR-98-5p | 1x positive association [78] | Moderate evidence of positive association | ||
| miR-139-3p | 1x negative association [78] | Moderate evidence of negative association | ||
| miR-146a-5p | 1x positive association [78] | 1x positive association [79] | Moderate evidence of positive association | |
| miR-203a | 1x negative association [78] | Moderate evidence of negative association | ||
| miR-486-5p | 1x negative association [78] | Moderate evidence of negative association | ||
| miR-1180-3p | 1x negative association [78] | Moderate evidence of negative association | ||
| miR-2379-5p | 1x positive association [78] | Moderate evidence of positive association | ||
| miR-3158-3p | 1x negative association [78] | Moderate evidence of negative association | ||
| miR-4732-3p | 1x negative association [78] | Moderate evidence of negative association | ||
| mRNA expression whole blood | CCL1 | 1x negative association [80] | Moderate evidence of negative association | |
| CCL7 | 1x negative association [80] | Moderate evidence of negative association | ||
| CCL20 | 1x negative association [80] | Moderate evidence of negative association | ||
| CX3CL1 | 1x negative association [80] | Moderate evidence of negative association | ||
| CXCL2 | 1x negative association [80] | Moderate evidence of negative association | ||
| CXCL5 | 1x negative association [80] | Moderate evidence of negative association | ||
| HAT1 | 1x positive association [81] | Limited evidence of positive association | ||
| IL-3 | 1x negative association [80] | Moderate evidence of negative association | ||
| IL-6 | 1x negative association [80] | Moderate evidence of negative association | ||
| IL-8 | 1x negative association [80] | Moderate evidence of negative association | ||
| IL-17C | 1x negative association [80] | Moderate evidence of negative association | ||
| IL-17F | 1x negative association [80] | Moderate evidence of negative association | ||
| ISG20 | 1x negative association [80] | Moderate evidence of negative association | ||
| MMP-3 | 1x negative association [80] | Moderate evidence of negative association | ||
| NOTCH2NL | 1x negative association [81] | Limited evidence of negative association | ||
| SET2D | 1x negative association [81] | Limited evidence of negative association | ||
| STAT3 | 1x negative association [80] | Moderate evidence of negative association | ||
| STAT6 | 1x negative association [80] | Moderate evidence of negative association | ||
| SYK | 1x negative association [80] | Moderate evidence of negative association | ||
| TBX21 | 1x negative association [80] | Moderate evidence of negative association | ||
| Serum | CD5L | 1x positive association [54] | Moderate evidence of positive association | |
| Creatinine | 1x no association [43] | 1x no association [53] | Moderate evidence of no association | |
| Complement C9 | 1x negative association [82] | Limited evidence of negative association | ||
| IFI16 | 1x negative association [83] | Moderate evidence of negative association | ||
| sIL2R | 1x positive association [61] | Moderate evidence of positive association | ||
| ITGB5 | 1x positive association [54] | Moderate evidence of positive association | ||
| Gelsolin | 1x negative association [44] | Limited association of negative association | ||
| K17 | 1x positive association [84] | Limited evidence of positive association | ||
| M2BP | 1x positive association [54] | Moderate evidence of positive association | ||
| MPO | 1x positive association [54] | Moderate evidence of positive association | ||
| PRL | 1x positive association [85] | Limited evidence of positive association | ||
| STIP1 | 1x positive association [84] | Limited evidence of positive association | ||
| Uric acid |
1x positive association [86] 1x no association [87] |
1x no association [88] 1x negative association [77] |
Conflicting evidence | |
| VCP | 1x positive association [89] | Limited evidence of positive association | ||
| VEGFR-3 | 1x positive association [90] | Limited evidence of positive association | ||
| YKL-40 | 1x positive association [91] | Limited evidence of positive association | ||
| Skin | C16ORF61 | 1x positive association [92] | Limited evidence of positive association | |
| CPN2 | 1x positive association [92] | Limited evidence of positive association | ||
| CXCL12 | 1x positive association [93] | Limited evidence of positive association | ||
| FHL1 | 1x positive association [92] | Limited evidence of positive association | ||
| GPS1 | 1x positive association [92] | Limited evidence of positive association | ||
| IL23R | 1x positive association [94] | Limited evidence of positive association | ||
| ITGB5 | 1x positive association [92] | Limited evidence of positive association | ||
| POSTN | 1x positive association [92] | Limited evidence of positive association | ||
| PP2R4 | 1x positive association [92] | Limited evidence of positive association | ||
| SNCA | 1x positive association [92] | Limited evidence of positive association | ||
| SRP14 | 1x positive association [92] | Limited evidence of positive association | ||
| SRPX | 1x positive association [92] | Limited evidence of positive association | ||
| Miscellaneous | Anti-ADAMTS-L5 IgG antibodies | 1x positive association [95] | Limited evidence of positive association | |
| Anti-LL37 antibodies |
1x positive association [95] 1x mixed results [82] |
Conflicting evidence | ||
| Arylesterase activity | 1x positive association [72] | Limited evidence of positive association | ||
| Hemoglobin | 1x negative association [70] | Limited evidence of negative association | ||
| IgG response to C region of rM12 protein | 1x positive association [96] | Limited evidence of positive association |
A positive association is defined as a higher risk of PsA when the marker is present/increased/higher. A negative association is defined as a lower risk of PsA when the marker is present/increased/higher
ACPA anti citrullinated protein antibodies, ADAMTS a disintegrin and metalloproteinase with thrombospondin motifs; anti-CCP, anti-cyclic citrullinated protein; Apo apolipoprotein, C16ORF61 endosomal protein sorting factor like (VSP35L), C2C collagen fragment neoepitopes Col2-3/4 (long mono), CCL C-C chemokine ligand, CCR C-C chemokine receptor, CD, cluster of differentiation, CD5L CD5 ligand, CER ceramide, CM central memory, COMP cartilage oligomeric matrix protein, CPII C-propeptide of type II collagen, CPN2 carboxypeptidase N subunit 2, CRP C-reactive protein, CTX collagen type I C-telopeptide, CX3CL C-X3-C motif ligand, CXCL C-X-C motif ligand, CXCR C-X-C motif receptor, DKK Dickkopf, EM effector memory, ESR erythrocyte sedimentation rate, FHL1 four and a half LIM domains, GPS G protein pathway suppressor, HAT human airway trypsin-like protein, HDL high-density lipoprotein, Hp hydroxyproline, IFI interferon-inducible protein, IFN interferon, IgG immunoglobulin G, IL interleukin, IL23R IL23 receptor, ISG interferon stimulated gene, ITGB integrin beta, K17, keratin 17, LDL low-density lipoprotein, M2BP Mac-2-binding protein, M-CSF macrophage colony-stimulating factor, MCV mutated citrullinated vimentin, miRNA micro RNA, MMP matrix metalloproteinase, MPO myeloperoxidase, mRNA messenger RNA, OPG osteoprotegerin, POSTN periostin, PPP2R4 protein phosphatase 2 phosphatase activator (PTPA);PRL, prolactin, RANKL receptor activator of nuclear factor kappa-B ligand, RNA ribonucleic acid, SETD SET domain protein, sIL-2R soluble IL-2 receptor, SNCA synuclein alpha, SRP signal recognition particle, SRPX sushi repeat containing protein X-linked, STAT signal transducer and activator of transcription, STIP stress-inducible phosphoprotein, SYK spleen-associated tyrosine kinase, TBX T-box, TNF tumor necrosis factor, VCP valosin-containing protein, VEGFR vascular endothelial growth factor receptor, VLDL very low-density lipoprotein