Table 3.

Summary details of studies examining candidate biomarkers of psoriasis progression

Study/number of psoriasis patients	Biomarker type/study design	Biomarker(s) examined	Number of key prognostic factors adjusted for	Outcome(s)/key results
HLA‐C*06:02
Douroudis et al. 29	Genomic/case–control	1: HLA‐C*06:02	2: Age, sex	PsA and hypertension: hypertension (OR 0·73, 95% CI 0·61–0·88) and PsA (OR 0·68, 95% CI 0·58–0·80) were significantly associated with HLA‐C*06:02‐negative status in fully adjusted model
N = 9286
Eder et al. 29	Genomic/case–control	10: HLA alleles	1: Age of onset	PsA: HLA‐C*06 was less frequent in the PsA group than in the PsC group (OR 0·58, P < 0·001). This result remained significant in the early‐onset psoriasis subgroup but not the late‐onset subgroup
N = 1047
Gudjonsson et al. 27	Genomic/cross‐sectional	1: HLA‐Cw*0602	1: Age of onset	Severity: significant association between Cw*0602 positive status and disease severity (P < 0·001). Late onset in patients who were Cw*0602‐positive was associated with less severe psoriasis compared with those with early onset (P = 0·0028, r = −0·13)
N = 1019
Gudjonsson et al. 25	Genomic/cross‐sectional	1: HLA‐Cw6 allele	No review‐specified key prognostic factors controlled for	Severity: mean disease severity score was higher in the Cw6+ group (1·67 vs. 1·45, P = 0·005). The difference between the groups increased when excluding patients with PsA (1·62 vs. 1·27, P < 0·001). No results reported for severity scoring based only on the extent of the skin lesions. Mean age at onset was 17·2 years in the Cw6+ group compared with 24·5 years in the Cw6− group
N = 369				PsA: no significant difference between groups, P = 0·135
Julia et al. 26	Genomic/ Case–control	32: loci with previous genome‐wide evidence of association with psoriasis	1: Age of onset	Severity: HLA‐C‐positive status associated with severe disease. OR 1·29 (95% CI 1·11–1·51, P = 0·033 after correction for multiple testing)
N = 2005				PsA: HLA‐C‐positive status was significantly associated with PsC in comparison with PsA (P = 1·69 × 10−6)
Suomela et al. 20	Genomic/cross‐sectional	2: HLA‐Cw6, HCR (CCHCR1)	2: Sex, age of onset	Severity: statistically significant lower PASI in patients who were Cw6+ compared with Cw6− (P < 0·007) but mean PASI were not reported
N = 379
HLA‐B*27, HLA‐B3*8 & HLA‐B*08
Eder et al. 28	Genomic/case–control	10: HLA alleles	1: Age of onset	PsA: Multivariate regression analysis results. Three HLA alleles more frequent in PsA than in psoriasis: HLA‐B*27 (OR 5·17, P < 0·001), HLA‐B*08 (OR 1·61, P = 0·009) and HLA‐B*38 (OR 1·65, P = 0·026)
N = 1047
IL12B, IL23A & IL23R
Eiris et al. 31	Genomic/cross‐sectional	5: IL12B, IL23R and IL23A polymorphisms	No review‐specified key prognostic factors controlled for	Severity: IL23R rs11209026 GG vs. AG + AA. GG associated with severity, OR 2·11 (95% CI 1·13–3·95), P = 0·02
N = 405				PsA: IL23R rs11209026 GG vs. AG + AA. OR 2·77 (95% CI 1·15–6·68)
				Type 2 diabetes: significant associations with IL12B rs6887695‐CC (OR 2·90, 95% CI 1·09–7·69, P = 0·03), IL12B rs3212227‐CC (OR 5·90, 95% CI 1·35–25·73, P = 0·035) and IL23R rs2201841‐GG (OR 2·69, 95% CI 1·09–6·66, P = 0·027). BMI reported as confounding the rs6887695 result. No other significant diabetes associations
Nikamo et al. 32	Genomic/case–control	20: Genes involved in the IL‐23 and NF‐κB signalling pathway	2: Sex, age of onset	Severity: after multiple testing correction – common IL‐23R (rs7530511) allele associated with disease severity – OR 0·71 (95% CI 0·57 to 0·88, P = 0·002). IL‐23A (rs2066808) [OR 0·53 (95% CI 0·37 to 0·76, P < 0·001)] and IL‐23R (rs2201841) [OR 1·26 (95% CI 1·07 to 1·48, P = 0·006)]
N = 1411
LCE3D
Julia et al. 26	Genomic/case–control	32: Loci with previous genome‐wide evidence of association with psoriasis	1: Age of onset	Severity: having two copies of the LCE3D risk allele was associated with moderate‐to‐severe disease, OR1·38 (95% CI 1·19–1·59, Pc = 0·0005)
N = 2005
NFKBIL1
Nikamo et al. 32	Genomic/case–control	20: Genes involved in the IL‐23 and NF‐κB signalling pathway	2: Sex, age of onset	Severity: minor NFKBIL1 allele associated with severe disease: OR 1·39 (95% CI 1·12–1·72, P = 0·002)
N = 1411
IL13
Eder et al. 40	Genomic/case–control	3: IL13 polymorphisms	No review‐specified key prognostic factors controlled for	PsA: the combination of non‐smoking and rs1800925*CC was associated with increased risk of PsA (OR 2·04, 95% CI 1·37–3·03, P < 0·001)
N = 897
IgG aHDL
Paiva‐Lopes et al. 41	Proteomic/cross‐sectional	4: IgG aHDL, aApoA‐I, aApoE, and aPON1 antibodies	2: Sex, age of onset	Severity: in the multivariate regression IgG aHDL was significantly associated with PASI; β coefficient 1·02 (P < 0·001). Patients with PASI > 10 had higher mean levels of IgG aHDL (P = 0·010). Comorbidities such as hypertension and diabetes mellitus were not associated with antibodies (P‐values between 0·23 and 1·00)
N = 67
GlycA
Joshi et al. 42	Proteomic/cross‐sectional	1: GlycA	1: Sex	Severity: in multivariate regression analyses, adjusting for all variables, GlycA correlated with psoriasis severity assessed by BSA. Cohort 1: β coefficient 0·21 (P = 0·01); Cohort 2: β coefficient 0·40 (P < 0·001). No adjusted results for categorical severity
N = 273 (cohort 1: n = 122; cohort 2: n = 151)
I‐FABP
Sikora et al. 43	Proteomic/case–control	1: Intestinal fatty acid binding protein (I‐FABP)	1: Sex	Severity: after adjustment for all covariates I‐FABP was significantly associated with moderate‐to‐severe disease: OR 3·47 (95% CI 1·20–10·07, P < 0·05) for each 100 pg mL−1 increase
N = 80
Kallikrein 8
Eissa et al. 44	Proteomic/case–control	7: Kallikreins	1: Sex	Severity: in the multivariate regression KLK8 correlated positively with PASI (r = 0·43, P = 0·001)
N = 152
CXCL10
Abji et al. 18	Proteomic/longitudinal	2: CXCL10, CRP	No review‐specified key prognostic factors controlled for	PsA: an increase of 100 pg mL−1 in baseline CXCL10 resulted in a 30% increase in the odds of progression to PsA (OR 1·3, 95% CI 1·1–1·5, P = 0·004). CXCL10 significantly higher in converters at baseline (median 927 pg mL−1) than after PsA diagnosis (median 492 pg mL−1), P < 0·001
N = 91
Abji et al. 17	Proteomic/longitudinal	1: CXCL10	No review‐specified key prognostic factors controlled for	PsA: significant decline in CXCL10 levels over time prior to PsA development in converters (to PsA, P < 0·001) but not in nonconverters. There was significant evidence of a difference in the trend of CXCL10 levels between converters and nonconverters (P = 0·02) at preconversion
N = 81
Mac‐2 binding protein and integrin b5
Cretu et al. 21	Proteomic/case–control	6: CD5‐like protein, myeloperoxidase, CRP, Mac‐2‐binding protein (M2BP), integrin b5 (ITGβ5), matrix MMP‐3	2: Sex, age of onset	PsA: multivariate regression suggested that two of the three biomarkers were associated with PsA, compared with psoriasis without PsA. ORs relate to a twofold protein level increase: ITGβ5: OR 3·82 (95% CI 2·18–6·70), M2BP: OR 32·32 (95% CI 4·90–213·3). Additionally, ITGβ5 and M2BP levels were significantly correlated with each other, r = 0·24
N = 200
MMP‐3 and M‐CSF
Jadon et al. 19	Proteomic/cross‐sectional	4: Osteoprotegerin, dickkopf‐1; macrophage‐colony stimulating factor (M‐CSF); matrix metalloproteinase‐3 (MMP3)	2: Sex, age of onset	PsA: MMP‐3 concentrations were significantly higher in patients with PsA compared with no‐PsA [adjusted OR 1·02 per ng mL−1 increase; 95% CI 1·01–1·03 (P = 0·001)]
N = 444				Patients with PsA had significantly lower M‐CSF concentrations than no‐PsA [adjusted OR 0·44 per ng mL−1 increase 95% CI 0·24–0·82 (P = 0·01)]
Chandran et al. 45	Mixed/cross‐sectional	12: IL‐12, IL‐12p40, IL‐17, TNFSF14, MMP‐3, RANK ligand, osteoprotegerin (OPG), cartilage oligomeric matrix protein, C‐propeptide of type II collagen (CPII), collagen fragment neoepitopes Col2‐3/4 (C2C), Col2‐3/4short and CRP	2: Sex, age of onset	PsA: multivariate model results indicated that increased levels of MMP‐3 (OR 1·28, 95% CI 1·02–1·60; P = 0·03) were independently associated with PsA when compared with patients with psoriasis only
N = 52
Tyramine and mucic acid
Kishikawa et al. 46	Metabolomic/cross‐sectional	417 metabolites	2: Sex, age	Severity: significant correlations between PASI scores and levels of tyramine and mucic acid (P = 0·0019 and P = 0·014, respectively)
N = 92				PsA: significantly increased tyramine levels in patients with PsA compared with PsC (P = 1·4 × 10−5)

N, number of patients with psoriasis; PsA, psoriatic arthritis; PsC, cutaneous psoriasis; BMI, body mass index; OR, odds ratio; CI, confidence interval; IL, interleukin; CRP, C‐reactive protein; NF‐κB, nuclear factor kappa B. Further study details and full quality assessment details are provided in Appendix S1 (see Supporting Information).