Review of biomarkers in systemic juvenile idiopathic arthritis: helpful tools or just playing tricks?

Gohar, Faekah; Kessel, Christoph; Lavric, Miha; Holzinger, Dirk; Foell, Dirk

doi:10.1186/s13075-016-1069-z

Arthritis Research & Therapy

Table 3 Identified serum and plasma biomarkers

From: Review of biomarkers in systemic juvenile idiopathic arthritis: helpful tools or just playing tricks?

Biomarker		Detection method	Intended use (P/D) + Reference		BMS score^a Q1 + Q2 + Q3 + Q4 + Q5 = total
Abbreviation/gene name	Full/alternative name		D	P
A2M	Alpha-2-macroglobulin	Commercial ELISA		[45]	1 + 0 + 0 + 1 + 0 = 2
AB-oxLDL	Antibodies to oxidized low-density lipoprotein	Commercial ELISA	[68]		1 + 0 + 0 + 1 + 0 = 2
ACAN	Aggrecan core protein, cartilage-specific core protein	Immunoassay	[69]		1 + 0 + 0 + 1 + 0 = 2
ACPA	Anti-citrullinated protein antibodies	Commercial ELISA	[39]	[39]	1 + 0 + 0 + 1 + 0 = 2
ACT	Alpha-1-antichymotrypsin	Commercial ELISA		[45]	1 + 0 + 0 + 1 + 0 = 2
AECA	Anti-endothelial cell antibodies	In-house ELISA	[70]		1 + 0 + 0 + 1 + 0 = 2
AGP1	Alpha-1-acid-glycoprotein	Commercial ELISA		[45]	1 + 0 + 0 + 1 + 0 = 2
ANA	Antinuclear antibody	Fluorescence assay		[36]	1 + 1 + 0 + 1 + 0 = 3
ANA	Antinuclear antibody	Commercial ELISA		[37]	1 + 1 + 0 + 1 + 0 = 3
Anti-BiP	Anti-immunoglobulin binding protein/glucose regulated protein 78 (GRP78)	In-house ELISA	[71]		1 + 0 + 0 + 1 + 0 = 2
Anti-CCP	Anti-cyclic citrullinated peptide	Commercial ELISA	[72]		1 + 0 + 0 + 1 + 0 = 2
APO A1	Apolioprotein A1	Commercial ELISA		[45]	1 + 0 + 0 + 1 + 0 = 2
APO VI	Apolipoprotein VI	Commercial ELISA		[45]	1 + 0 + 0 + 1 + 0 = 2
APRIL	A proliferation-inducing ligand	Commercial ELISA	[73]	[73]	1 + 0 + 0 + 1 + 0 = 2
B2M	Beta -2-microglobulin	Not indicated		[74]	1 + 0 + 0 + 1 + 0 = 2
BAFF	B-cell activating factor	Commercial ELISA	[73]	[73]	1 + 0 + 0 + 1 + 0 = 2
C4	Complement C4	Commercial ELISA		[45]	1 + 0 + 0 + 1 + 0 = 2
CCL3	Chemokine (C-C motif) ligand 3	Luminex assay	[57]		1 + 0 + 0 + 1 + 0 = 2
CD10	Cluster of differentiation antigen 10, also called neprilysin	Fluorimetric assay	[75]		1 + 0 + 0 + 1 + 0 = 2
CFH	Complement factor H	Commercial ELISA		[45]	1 + 0 + 0 + 1 + 0 = 2
COMP	Cartilage oligomeric matrix protein	Commercial ELISA	[39]	[39]	1 + 1 + 0 + 1 + 0 = 3
			[76]	[77]
			[76]	[78]
CXCL9	Chemokine (C-X-C Motif) ligand 9	Luminex assay	[57]		1 + 0 + 0 + 1 + 0 = 2
Fibrin D-dimer		Commercial assay		[79]	1 + 0 + 0 + 1 + 0 = 2
FSTL-1	Follistatin-like protein 1	Commercial ELISA	[80]	[80]	1 + 1 + 0 + 1 + 0 = 3
FSTL-1	Follistatin-like protein 1	Commercial ELISA	[80]	[81]	1 + 1 + 0 + 1 + 0 = 3
GHRL	Ghrelin, appetite regulating hormone	Commercial ELISA	[82]		1 + 0 + 0 + 1 + 0 = 2
GSN	Gelsolin	Commercial ELISA		[45]	1 + 0 + 0 + 1 + 0 = 2
Hepcidin	Peptide hormone, released by hepatocytes	Commercial assay	[22]		1 + 0 + 0 + 1 + 0 = 2
HMGB1	High mobility group box protein 1	Commercial assay	[83]		1 + 0 + 0 + 1 + 0 = 2
HO-1	Heme oxygenase-1	Commercial ELISA	[84]	[85]	1 + 1 + 0 + 1 + 1 = 4
HP	Haptoglobin	Commercial ELISA		[45]	1 + 0 + 0 + 1 + 0 = 2
IFNg	Interferon gamma	Commercial ELISA	[86]	[86]	1 + 0 + 0 + 1 + 0 = 2
IgA RF	Ig A rheumatoid factor isotype	In-house ELISA	[87]		1 + 0 + 0 + 1 + 0 = 2
IgM RF	Ig M rheumatoid factor isotype	In-house ELISA	[87]		1 + 0 + 0 + 1 + 0 = 2
IL-10	Interleukin-10	Commercial ELISA	[88]	[85]	1 + 0 + 0 + 1 + 0 = 2
IL-12	Interleukin-12	Luminex assay	[57]		1 + 1 + 1 + 1 + 0 = 4
IL-12	Interleukin-12	Commercial ELISA	[89]		1 + 1 + 1 + 1 + 0 = 4
IL-18	Interleukin-18	Commercial assay Luminex assay	[25]		1 + 1 + 1 + 1 + 0 = 4
			[57]	[24]
			[86]	[90]
			[90]	[91]
			[92]
IL-18BP	Interleukin-18 binding protein	Commercial assay	[86]		1 + 1 + 0 + 1 + 0 = 3
IL-18BP	Interleukin-18 binding protein	Commercial assay	[90]	[90]	1 + 1 + 0 + 1 + 0 = 3
IL-1b	Interleukin-1beta	Commercial ELISA	[89]		1 + 0 + 0 + 1 + 0 = 2
IL-6	Interleukin-6	Luminex assay Commercial ELISA	[57]	[24]	1 + 1 + 1 + 1 + 0 = 4
			[86]
			[89]
			[76]
IP-10/CXCL10	IFNg-induced protein 10, or C-X-C motif chemokine 10	Commercial ELISA Luminex assay	[57]		1 + 1 + 0 + 1 + 0 = 3
			[86]
			[93]
LGALS3	Galectin-3	Commercial ELISA	[94]		1 + 0 + 0 + 1 + 0 = 2
MIF	Macrophage migration inhibitory factor	Luminex assay	[57]		1 + 0 + 0 + 1 + 0 = 2
MMP-3	Matrix metalloprotinease-3/stromelysin-1 (SL-1)	Commercial ELISA	[72]		1 + 0 + 0 + 1 + 0 = 2
Neopterin		Commercial ELISA		[85]	1 + 0 + 0 + 1 + 0 = 2
NO	Nitric oxide	Spectrophotometry		[95]	1 + 0 + 0 + 1 + 0 = 2
OPG	Osteoprotegerin/TNF 11B	Luminex assay Commercial ELISA	[57]		1 + 1 + 1 + 1 + 0 = 4
OPG	Osteoprotegerin/TNF 11B	Luminex assay Commercial ELISA	[96]		1 + 1 + 1 + 1 + 0 = 4
OPN	Osteopontin, phosphoglycoprotein	Commercial ELISA	[97]		1 + 0 + 0 + 1 + 0 = 2
RA33	Anti-heterogeneous nuclear ribonucleoprotein A2 antibodies	Commercial ELISA	[98]		1 + 0 + 0 + 1 + 0 = 2
RANKL	TNF ligand superfamily member 11/receptor activator of nuclear factor kappa B ligand	Commercial ELISA	[96]		1 + 0 + 0 + 1 + 0 = 2
Resistin	Protein adipokine	Commercial ELISA	[99]		1 + 0 + 0 + 1 + 0 = 2
S100A12	S100 calcium-binding protein A12	In-house ELISA Commercial ELISA	[45]	[45]	1 + 1 + 1 + 1 + 0 = 4
			[100]	[100]
			[101]	[102]
S100A8/A9	MRP8/14 (myeloid regulatory protein 8/14) complex, complex of S100A8 (Calgranulin A) and S100A9 (Calgranulin B)	In-house ELISA Commercial ELISA	[23]		1 + 1 + 1 + 1 + 0 = 4
			[45]	[23]
			[101]	[17]
			[103]	[45]
SAA	Serum amyloid A	Commercial ELISA	[45]	[45]	1 + 1 + 0 + 1 + 0 = 3
SAA	Serum amyloid A	Commercial ELISA	[76]		1 + 1 + 0 + 1 + 0 = 3
SAP	Serum amyloid P	Commercial ELISA		[45]	1 + 0 + 0 + 1 + 0 = 2
sCD163	Soluble cluster of differentiation 163/haemoglobin scavenging receptor	Commercial ELISA		[85]	1 + 1 + 0 + 1 + 0 = 3
sCD163		Commercial ELISA		[104]	1 + 1 + 0 + 1 + 0 = 3
sCD21	Soluble cluster of differentiation 21	Commercial ELISA	[105]		1 + 0 + 0 + 1 + 0 = 2
sCD23	Soluble cluster of differentiation 23/soluble low affinity immunoglobulin epsilon Fc receptor)	Commercial ELISA	[105]		1 + 0 + 0 + 1 + 0 = 2
sCD25	Soluble cluster of differentiation 25/soluble interleukin-2 receptor alpha	Commercial ELISA		[74]	1 + 1 + 0 + 1 + 0 = 3
				[104]
				[106]
				[107]
sE-selectin	Soluble E-selectin adhesion molecule	Commercial ELISA	[108]		1 + 1 + 0 + 1 + 0 = 3
			[109]
			[110]
sICAM-1	Soluble intracellular adhesion molecule-1	Commercial ELISA	[108]		1 + 1 + 0 + 1 + 0 = 3
			[109]
			[110]
sRAGE	Soluble receptor for advanced glycation end products	Commercial assay	[83]		1 + 0 + 0 + 1 + 0 = 2
sST2	Soluble ST2, also called interleukin 1 receptor-like 1 (IL-1RL1)	Commercial ELISA	[111]	[111]	1 + 0 + 0 + 1 + 0 = 2
sTM	Soluble thrombomodulin/CD141	Commercial ELISA	[112]		1 + 0 + 0 + 1 + 0 = 2
sTNFR55	Soluble tumour necrosis factor receptor 55	Commercial ELISA	[113]		1 + 0 + 0 + 1 + 0 = 2
sTNFR75	Soluble tumour necrosis factor receptor 75	Commercial ELISA	[113]		1 + 0 + 0 + 1 + 0 = 2
Survivin		Commercial ELISA	[76]		1 + 0 + 0 + 1 + 0 = 2
TIMP	Tissue inhibitors of metalloproteinases	Commercial ELISA	[96]		1 + 0 + 0 + 1 + 0 = 2
TNF-alpha	Tumour necrosis factor-alpha	Commercial ELISA	[88]		1 + 0 + 0 + 1 + 0 = 2
TTR	Transthyretin	Commercial ELISA	[45]	[45]	1 + 0 + 0 + 1 + 0 = 2

^aBiomarker scoring system (BMS) biomarker score: each answer is scored as follows: yes = 1, no = 0. D diagnostic, P prognostic, Q1 readily measurable (e.g. in serum), Q2 measured by more than one independent study group, Q3 discovered by more than one single method, Q4 measured by a reproducible assay, Q5 validated in a validation cohort, IFN interferon, TNF tumour necrosis factor

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