Table 2.
Included Prognostic Biomarkers Studies.
| References | Publication year | Study design | PsA (n) | Classification criteria | Biomarkers | Methodology | Outcome |
|---|---|---|---|---|---|---|---|
| Acute Phase Reactant Biomarkers | |||||||
| Helliwell (84) | 1991 | Cross-sectional | 36 | Moll & Wright | Cytidine deaminase; ESR; CRP; histidine | Concentration assessment in 36 PsA blood samples. | Better correlation with disease activity was ESR. |
| Mchugh (85) | 2003 | Prospective | 87 | Moll & Wright | ESR | 5-year follow-up of a cohort of 87 PsA patients. | Correlation between high initial ESR level and pejorative disease progression. |
| Bandinelli (86) | 2015 | Cross-sectional | 112 | CASPAR | ESR; CRP; Anti-CCP; HLA | US examination, HLA typing and serum analysis of 112 patients with PsA. | US abnormalities were associated with higher mean serum CRP or ESR levels and expression of HLA-B27, B-35, B38, Cw*6 and DR4. |
| Bone and cartilage biomarkers | |||||||
| Kane (87) | 2003 | Retrospective | 22 | Moll & Wright | MRP8; MRP 14 | ELISA analysis of synovial and serum sample from 22 patients with PsA, 11 with RA 15 with SpA. | Serum MRP8 and MRP14 concentrations were markers of disease activity in PsA, RA and SpA. |
| Skoumal (88) | 2008 | Cross-sectional | 64 | Moll & Wright | COMP | ELISA analysis of serum from 64 patients with PsA and 39 with PsO. | COMP concentration was significantly correlated with CRP, ESR, TCJ and SCJ. |
| Dalbeth (89) | 2010 | Cross-sectional | 38 | CASPAR | Dkk-1; M-CSF; RANK-L; OPG | Serum analysis from 38 PsA, 10 PsO and 12 HC. | RANK-L and M-CSF are correlated with articular radiographic damage in PsA. |
| Van kuijk (90) | 2010 | Prospective | 24 | CASPAR | CPII; PINP; MIA; MMP-3; C2C; COMP; osteocalcin; NTX-1; CTX-1 | Serum analysis using ELISA for 12 weeks follow-up of 24 PsA in an adalimumab study. | Decreased MMP-3 concentration was associated with DAS28 improvement. |
| Ramonda (91) | 2013 | Prospective | 43 | CASPAR | MMP3; VEGF; PTX3; hsCRP | ELISA analysis on 43 HC and 43 PsA at inclusion and 24 weeks after anti-TNF introduction. | Decrease in biomarker levels during follow-up. |
| Waszczykowski (18) | 2021 | Cross-sectional | 24 | CASPAR | IL-18; IL-20; MMP-1; MMP-3; COMP; YKL-40; Aggrecan | ELISA analysis from 24 patients with active PsA sera and 26 HC. | COMP level was significantly correlated with TJC and SJC. |
| Chung (92) | 2021 | Cross-sectional | 69 | CASPAR | Dkk-1 | ELISA analysis from 69 PsA sera, 39 RA and 21 HC. Radiographic hands erosions and sacroiliitis were assessed. | Bone erosions, sacroiliitis and SCJ were correlated with elevated serum levels of Dkk-1. |
| Genetic biomarkers | |||||||
| Alenius (93) | 2002 | Cross-sectional | 88 | Moll & Wright | HLA-A; HLA-B; HLA-Cw*; HLA-DRB1*; HLA-DQB1* | HLA Genotyping of 88 PsA and 1085 HC. | HLA-B37 and HLA-B62 were markers of erosions and deformations in PsA. |
| Iwaszko (41) | 2021 | Cross-sectional | 126 | CASPAR | IL-33 gene polymorphisms (rs16924159; rs10975519; rs7044343) | PCR analysis in 126 PsA, 143 AS, 466 RA and 229 HC. | No correlation between SNPs within IL-33 gene and CRP or BASDAI in PsA. |
| Autoantibodies | |||||||
| Korendowych (94) | 2005 | Cross-sectional | 126 | Physician diagnosis | Anti-CCP | Immunofluorescence analysis from 126 PsA sera. | All PsA CCP+ had radiographic damages and significantly higher SJC. |
| Perez-alamino (95) | 2014 | Prospective | 81 | CASPAR | Anti-CCP | ELISA assessment from 81 PsA sera. | PsA CCP+ had more erosive damage and higher polyarticular forms. |
| Ibrahim (96) | 2018 | Cross-sectional | 45 | CASPAR | Anti-CarP autoantibodies | ELISA analysis of sera from 45 patients with PsA and 45 HC. | Anti-CarP autoantibodies were associated to both clinical and US activity in PsA. |
| Frasca (48) | 2018 | Cross-sectional | 32 | CASPAR | Anti-LL37 carbamylated autoantibodies and Anti-LL37 citrullinated autoantibodies | ELISA analysis from 32 PsA sera, 24 PsO, and 12 HC. | Correlation with DAS44 in PsA. |
| Other biomarkers | |||||||
| Elkayam (97) | 2000 | Cross-sectional | 34 | Moll & Wright | Hyaluronic acid | Radiometric assay of sera 34 patients with PsA, 34 with RA and 49 with HC. | Hyaluronic acid level was correlated to PASI Score (r: 0.87). |
| Elkayam (98) | 2000 | Cross-sectional | 34 | Moll & Wright | IL-10; IL-6; IL-1ra; IL-2R | ELISA analysis of serum samples from 34 patients with PsA and 10 HC. | Increase in IL-1Ra titers associated with joint activity in PsA. |
| Foell (87) | 2003 | Prospective | 22 | Moll & Wright | Calprotectin S100A12 | Serum analysis before and after MTX introduction of 22 PsA patients, 9 RA patients, 11 SpA patients and 30 HC. | Calprotectin S100A12 concentration was modestly correlated with ESR and Richie index. |
| Rooney (99) | 2004 | Prospective | 5 | Moll & Wright | IL-18 | Monitoring expression in synovial tissues from 5 patients with PsA, 11 with RA, 9 with UA and 2 with reactive arthritis before MTX or Salazopyrine introduction, repeated after 12 months delay. | IL-18 expression correlated with CRP circulating levels in all groups before treatment. Decrease expression of IL-18 after treatment correlated with a decrease in CRP levels. |
| Fink (100) | 2007 | Cross-sectional | 28 | Moll & Wright | VEGF | ELISA analysis of sera from 28 patients with PsA and 9 HC. | Higher VEGF titres in the active PsA subgroup. |
| Madland (101) | 2007 | Cross-sectional | 119 | Physician diagnosis | ESR; hsCRP; Calprotectin S100A8/A9; Calprotectin S100A12 | Serum analysis from 119 PsA patient blood samples. | Calprotectin S100A8/A9 was inferior to ESR and CRP to assess disease activity but was a better marker of radiographic damage. |
| Szodoray (52) | 2007 | Cross-sectional | 43 | Moll & Wright | Panel of 23 different biomarkers | ELISA analysis from 43 patients with PsA sera and 25 HC. | EGF, IFNα, VEGF, CCL3 and IL-12 p-40 levels correlated with disease activity. |
| Alenius (102) | 2009 | Cross-sectional | 134 | Moll & Wright | IL-6; IL-2R | Serum analysis from 134 patients with PsA and 85 PsO patients using ELISA. | IL-6 is associated to ESR, CRP and TCJ. |
| Pongratz (103) | 2010 | Cross-sectional | 52 | CASPAR | BAFF and testosterone | Serum analysis from 53 PsA patient blood samples. | In male patients with PsA, the BAFF/testosterone ratio was significantly correlated with DAS28. |
| Celis (104) | 2011 | Cross-sectional | 46 | CASPAR | miRNA expression and panel of 21 cytokines. | ELISA analysis associated to quantitative RT-PCR of synovial tissues from 46 PsA. | Association between synovial IL-6 and CCL20 levels and circulating CRP levels. |
| Przepiera-będzak (105) | 2013 | Cross-sectional | 80 | CASPAR | VEGF; EGF; FGFβ; FGFα | Serum analysis on 80 PsA patient samples, 18 with SAPHO and 20 HC. | VEGF and CRP are correlated. VEGF is not associated with several disease activity score. |
| Jensen (106) | 2011 | Prospective | 42 | Moll & Wright | YKL-40 (Chi3l1); hsCRP | Serum analysis on 42 patients with PsA and 6 with PsO before and after adalimumab introduction. | YKL40 is decreased in responder PsA patients. |
| Eissa (107) | 2013 | Cross-sectional | 50 | CASPAR | Kallikreins | Serum analysis on 50 patients with PsA, 50 PsO patients and 26 HC. | Kallikrein 8 and Kallikrein 6 are associated with PASI in PsA patients. |
| Kayikci (108) | 2013 | Cross-sectional | 48 | CASPAR | Il-17; Il-22; Il-23 | ELISA analysis on 48 patients with PsA, 20 with PsO and 19 HC. | Il-17 is weakly correlated with TJC. |
| Hansson (54) | 2014 | Prospective | 65 | CASPAR | Calprotectin S100A8/S100A9 | ELISA analysis in sera from 65 patents with PsA and 31 HC. | Calprotectin was significantly increased in polyarticular form of PsA. |
| Ahmed (109) | 2015 | Cross-sectional | 26 | CASPAR | YKL-40 (Chi3l1) | ELISA analysis of blood samples from 26 pateints with PsA, 22 with PsO and 30 HC. | YKL40 was significantly correlated with CPDAI in PsA patients. |
| Husakova (110) | 2015 | Cross-sectional | 40 | Physician diagnosis | Prolactin | Immunoradiometric assay on sera of 70 patients with PsO, 40 with PsA and 27 HC. | No correlation was found with disease activity. |
| Matt (111) | 2015 | Cross-sectional | 23 | CASPAR | Fc receptor of Monocyte-cells | Flow cytometru on sera of 23 patients with PsA and 32 HC. | High titer of CD64+ cells was significantly correlated with DAS28. |
| Peled (112) | 2015 | Cross-sectional | 20 | CASPAR | PD1 | Flow cytometry on 20 patients with PsA and 15 HC. | A low titre of T-cell presenting PD1 is associated with a low DAS28 score. |
| Dikbas (113) | 2016 | Cross-sectional | 28 | CASPAR | Adipocytokine: Visfatin; Resistin; Adiponectin | ELISA analysis on 28 PsA patients and 39 HC. | No correlation found. |
| Munk (114) | 2016 | Cross-sectional | 101 | CASPAR | PIIANP; C2M | ELISA analysis of 110 patients with SpA, 101 with PsA and 96 HC. | No correlation found. |
| Alonso (64) | 2016 | Cross-sectional | 200 | Physician diagnosis | Urinary biomarker panel | Nuclear magnetic resonance analysis of urine samples from 200 patients with PsA, 200 with RA, 200 with PsO, 200 with SLE, 200 with Crohn’s disease, and 200 HC. | Increased urine levels of citrate in active PsA. |
| Inciarte-mundo (115) | 2016 | Cross-sectional | 50 | CASPAR | Calprotectin and TNF trough serum levels | Serum analysis from 50 patients with PsA and 42 with RA. | High Calprotectin titers were associated with US activity in both PsA and RA patients. |
| Przepiera (116) | 2016 | Cross-sectional | 76 | CASPAR | IL-18; Fetuin A; ICAM-1; ET-1 | ELISA analysis of sera from 76 patients with PsA sera, 81 with SpA and 34 with SAPHO. | ET-1 levels were correlated to DAS28 in PsA. IL-18 levels were associated to BASDAI. |
| Kiliç (117) | 2017 | Cross-sectional | 116 | CASPAR | MPV | Serum analysis from 116 PsA patients, 41 PsO patients and 90 HC. | Skin disease severity was associated to high MPV concentration in patients with PsA. |
| Farrag (68) | 2017 | Cross-sectional | 21 | CASPAR | IL-34 | ELISA assessment in sera from 21 patients with PsA, 24 with PsO and 20 HC. | Association between IL-34 and disease articular and PASI, CPDAI, and BASDAI. |
| Inciarte-mundo (118) | 2018 | Prospective | 51 | CASPAR | Calprotectin; TNF trough serum levels | Serum analysis at baseline and relapse of 47 PsA patients and 56 with RA treated with anti-TNF. | High Calprotectin concentration at baseline was associated with relapse in both PsA and RA patients. |
| Wade (119) | 2018 | Cross-sectional | N.A. | N.A. | Polyfunctional T-cells | Flow cytometry analysis on patients with PsA. | Th1 and Th17 pathways were associated with DAPSA. |
| Coras (120) | 2019 | Cross-sectional | 41 | CASPAR | Eicosanoids | Assessment using liquid phase chromatography and mass spectrometry on 41 patients with PsA. | 9 pro-inflammatory eicosanoids were associated to DAS28 while 18 anti-inflammatory eicosanoids were inversely correlated with it. |
| Colak (121) | 2019 | Cross-sectional | 50 | CASPAR | VASPIN; NGAL; Apolipoprotein | Serum analysis on 50 patients with PsA and 36 HC. | No significant correlation found with disease activity. |
| Sakellariou (122) | 2019 | Cross-sectional | 78 | CASPAR | Calprotectin | ELISA analysis from 78 patients with PsA sera and 78 with RA. | Modest correlation with US activity score. |
| Coras (123) | 2019 | Cross-sectional | 38 | CASPAR | Cholin metabolites | Liquid phase chromatography and mass spectrometry analysis on 38 PsA. | Trimethylamine-N-oxide was correlated to DAS28, CPDAI and BSA. |
| Ozisler (124) | 2020 | Retrospective | 47 | CASPAR | RDW | Blood samples analysed from 47 patients with PsA and 56 HC. | RDW was modestly correlated to DAS28, CRP and ESR in PsA patients. |
| Arias de la rosa (125) | 2020 | Cross-sectional | 80 | CASPAR | Complement C3 | Serum analysis on 80 patients with PsA, 200 with RA, 150 with SpA and 100 HC. | Higher C3 concentration in PsA population with DAS28> 5.1. |
| Esawy (71) | 2020 | Cross-sectional | 76 | CASPAR | Plasma Gelsolin | ELISA analysis of sera from 76 patients with PsA, 40 with PsO and 40 age- and sex-matched HC. | Negative correlation between Gelsolin titers and DAPSA or CPDAI. |
| Jarlborg (126) | 2020 | Cross-sectional | 237 | CASPAR | Calprotectin S100A8/S100A9 | Serum analysis on 969 RA patient blood samples, 451 patients with SpA, 237 PsA patients and 72 HC. | No correlation founded with disease activity in PsA patients. |
| Medvedeva (127) | 2020 | Prospective | 80 | N.A. | 155 different proteins | Immunoassay on sera from 80 pateints with PsA, 175 with SpA and 93 with PsO during different apremilast’s phase 3 studies. | No correlation founded with disease activity in PsA patients. |
| Wcisło-dziadecka (128) | 2020 | Prospective | 6 | CASPAR | TNF- α; TNFR1; TNFR2 | Mass spectrometry analysis from blood samples in 6 patients with PsA treated with adalimumab. | Serum TNF higher titers was associated with lower DAS28. |
| Boyd (129) | 2020 | Cross-sectional | 45 | CASPAR | Panel of 12 biomarkers | Immunoassays analysis in blood samples from 45 patients with PsA. | Moderate correlation between YKL-40, IL-6, ICAM-1, and composite score (SAA CDAI, SDAI, DAS28, HAQ and MDA). |
| Leijten (74) | 2021 | Prospective | 20 | CASPAR | 951 unique proteins | Serum proteomic analyses from 20 patients with PsA, 20 with PsO, 19 with AS and 20 HC. | ICAM-1 and CCL-18 levels were correlated with SCJ. PI3 correlated with PASI score. |
| Coras (130) | 2021 | Cross-sectional | 19 | CASPAR | Oxylipins profile | Reverse-phase chromatography analyses in sera from 19 patients with PsA and 20 with PsO. | Oxylipins profile correlated with skin activity in PsO and PsA patients but not with articular activity in PsA patients. |
PsA, psoriatic arthritis; PsO, psoriasis; HC, Healthy control; OA, Osteoarthritis; RA, Rheumatoid arthritis; LES, lupus erythematosus systemic; UA, Undifferentiated Arthritis; SpA, Spondyloarthritis; SAPHO, Synovitis Acne Pustulosis Hyperostosis Osteitis; CASPAR, Classification criteria for Psoriatic Arthritis; PASI, Psoriatic Area and Severity Index; BSA, Body Surface Area; DAS, Disease Activity Score; CPDAI, composite psoriatic disease activity index; DAPSA, Disease Activity in PSoriatic Arthritis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; ELISA, Enzyme-linked immune absorbent assay; MTX, Methotrexate; MRP, Myeloid Related Protein; IL, Interleukin; TNFSF, Tumor Necrosis Factor Super Family; CRP, C-reactive protein; TNF, Tumor necrosis factor; HLA, Human leukocyte antigen; VEGF, Vascular endothelial growth factor; Anti-CCP, Anti-cyclic citrullinated protein; anti-LL37, anti-cathelecidin; Anti-ADAMTS5, A disintegrin and metalloproteinase with thrombospondin motifs; ICAM-1, Intercellular adhesion molecule 1; ESR, Erythrocyte sedimentation rate; hsCRP, High sensitive c reactive protein; IFN, Interferon; COMP, Cartilage Oligomeric MetalloProteinase; TCJ, Tender Joint Count; SCJ, Swollen Joint Count; Blys, B lymphocyte Stimulator; BAFF, B cells activating factor belonging to TNF Family; M-CSF, Macrophage colony stimulating factor; MIA, melanoma inhibitory activity; NTX, N-terminal cross-linked telopeptide of type I collagen; ITCP, C-telopeptide of Type I Collagen; RT-PCR, reverse transcription and polymerase chain reaction; CCL-x, chemokine ligand-x; Chi3L1, Chitinase 3 like protein; PTX3, Pentraxin 3; PIIANP, procollagen IIA N-Terminal peptide; C2M, Matrix metalloproteinase-generated type II collagen fragment; MPV, Mean platelet volume; PD1, Programmed Death-1; ET-1, Endothelin 1; VASPIN, visceral adipose tissue-derived serine protease inhibitor; NGAL, Neutrophil-gelatinase associated lipocalin; Anti-CarP, Anti-Carbamethylated protein; RDW, Red blood cell distribution width; MMP3, Matrix MetalloProteinase-3; MDA, Minimal activity disease.