Salivary Cytokines as Potential Diagnostic Biomarkers for Systemic Lupus Erythematosus Disease

Table 1

Cytokine profiles identified in SLE patients.

Study	Subjects ()	Sample types	Cytokines measured	Analytical methods	Findings
Selvaraja et al. [61]	64 SLE patients (17 with and 47 without LN)/15 HC	Plasma	IL-25, IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13	ELISA and multiplex cytokine assay	(i) Significantly increased levels of IL-9, IL-10, and IL-25 in SLE patients with and without LN; (ii) Significantly reduced levels of IL-5 and IL-6; (iii) No significant difference was observed with IL-13; (iv) Level of IL-4 was undetectable; (v) IL-25, IL-9, and IL-10 were positively correlated with the disease severity score
Torell et al. [62]	310 SLE patients/310 HC	Serum	IFN-γ, IL-6, IL-8, IL-10, IL-15, IL-16, CXCL10, MCP-1, MIP-1α, MIP-1β, TNF-α	Mesoscale discovery multiplex analysis	(i) Increased serum levels of IL-10, TNF-α, IL-15, MIP-1α, CXCL10, MCP-1, IL-6, IFN-γ, MIP-1β, IL-16, IL-8 in SLE patients
Reynolds et al. [63]	96 SLE patients/13 HC	Serum	CXCL13, BLyS, IL-18, PTX3, CXCL10, IL-17, IFN-α, IL-10, IL-21, MCP-1	High-sensitivity bead-based multiplex ELISA	(i) Serum levels of BLyS, IL-17, IL-18, CXCL10, and PTX3 were significantly higher in SLE patients with active disease
Guimarães et al. [64]	200 SLE patients/196 HC	Plasma	IL-6, IL-12, IL-17, IFN-γ, IL-10, IL-4, TNF-α, IL-6, IL-1β	ELISA	(i) Significantly higher levels of IL-6, IL-12, IL-17, IFN-γ, and IL-10 in SLE; (ii) Lower levels of IL-4 in SLE; (iii) No significant differences in (TNF-α+IL-6+IL-1β) profile
Arora et al. [65]	40 SLE patients/40 HC	Serum	IL-4, IFN-γ, IL-10, and TNF-α	ELISA	(i) In HC: levels of IFN-γ were highest, followed by TNF-α, IL-10, and IL-4; (ii) In SLE patients: levels of TNF-α were highest, followed by IFN-γ, IL-10, and IL-4; (iii) IL-10 and IL-4 correlated negatively, and IFN-γ and TNF-α correlated positively with the SLEDAI scores
Shah et al. [66]	25 SLE patients/26 HC	Serum	IL-1β, IL-6, IL-10, TGF-β, IL-21, and IL-23	ELISA and multiplex cytokine assay	(i) Higher levels of IL-6 in SLE than HC; (ii) No differences in levels of IL-1β, IL-21, IL-23, and TGF-β between SLE and HC
Li et al. [67]	56 SLE patients/30 HC	Serum	IL-27	ELISA	(i) Significantly lower serum level of IL-27 in SLE
Yang et al. [68]	50 SLE patients/15 HC	Serum	IL-17A and IFN-γ	ELISA	(i) Higher levels of IL-17A in SLE patients with active disease
Petri et al. [69]	245 SLE patients	Serum	BLyS	ELISA	(i) Elevated BLyS serum levels were in SLE patients and correlate with disease activity
Chun et al. [38]	166 SLE patients/167 DC (90 with RA and 77 with AS) and 40 HC	Serum	IL-2, IL-6, IL-10, IL-12, IFN-γ	ELISA	(i) SLE patients had higher IL-6, IL-10, IL-12, and IFN-γ levels, but lower IL-2, than HC; (ii) Levels of IL-6 and IL-10 were significantly higher in active SLE patients and correlated with the SLE activity index (SLEDAI)
Niewold et al. [56]	266 SLE patients and their 405 healthy relatives/105 healthy unrelated	Serum	IFN-α	ELISA	(i) Serum level of IFN-α in both patients and healthy relatives was higher as compared to healthy unrelated individuals
Baranda et al. [70]	18 SLE patients/14 HC	Serum	IL-15, IFN-γ, and TNF-α	ELISA	(i) Increased serum levels of IL-15 in SLE patients
Capper et al. [71]	74 SLE patients/13 HC	Serum	IL-10, IL-12, IL-1RA	ELISA	(i) Higher levels of circulating IL-10 and IL-1RA in SLE patients; (ii) Significantly higher levels of circulating IL-12 in SLE patients
Gómez et al. [48]	52 SLE patients/25 HC	Serum	TNF-α, IFN-γ, IL-12p70, IL-10, IL-4	ELISA	(i) Levels of IFN-γ, TNF-α, and IL-12 were significantly higher in SLE patients
Calvani et al. [72]	133 SLE patients with and without LN/44 HC	Serum	IL-18, IFN-γ, IL-4	ELISA	(i) Higher serum IL-18 in SLE; (ii) High IFN-γ with low IL-4 expression in SLE patients with LN; (iii) A positive correlation between serum IL-18 and IFN-γ levels
McCarthy et al. [73]	45 SLE patients/20 HC	Serum	IFN-γ, TNF-α, IL-1β, IL-12p70, IL-10	ELISA	(i) Elevated levels of IL-1β, TNF-α, IFN-γ, and IL-10 in SLE; (ii) Increased levels of IL-12p70 coincided with increased levels of IL-10 in SLE patients; (iii) A significant relationship between IL-10, TNF-α, and IL-1 β and disease activity
Min et al. [74]	40 SLE patients (17 with LN and 23 without LN)/80 HC	Serum	IFN-γ, IL-12, IL-4, and IL-10	ELISA	(i) Significantly higher levels of serum IFN-γ, IL-12, IL-4, and IL-10 in SLE patients than HC; (ii) Significantly lower levels of serum IL-12 and IFN-γ in patients with LN compared to those without; (iii) Significantly higher levels of serum IL-10 in patients with LN compared to those without
Gröndal et al. [40]	52 SLE patients/29 HC	Serum	IL-6, IL-10	ELISA	(i) Serum levels of IL-10 and IL-6 were increased in SLE patients; (ii) Serum IL-10 levels correlated with the titer of anti-dsDNA antibodies in the patients
Tsai et al. [75]	27 LN patients (15 with active LN and 12 with inactive)/17 HC	Urine	IL-6, IL-8, IL-2R, and β2M	ELISA	(i) The urinary excretions of IL-6 and IL-8 were significantly higher in patients with active LN than in those with inactive LN and HC; (ii) The urinary β2M excretion in LN patients was significantly higher than that in HC
Wong et al. [76]	36 SLE patients/18 HC	Serum	IL-17, IL-12, IL-18, and IL-4	ELISA	(i) Increased serum levels of IL-12, IL-17, IL-18, and IL-4 in SLE patients

AS: ankylosing spondylitis; BD: Behcet’s disease; BLyS: B-lymphocyte stimulator; β2M: beta 2-microglobulin; CNS: central nervous system; CSF: cerebrospinal fluid; DC: disease control; ELISA: enzyme-linked immunosorbent assay; HC: healthy controls; IL: interleukins; IL-1RA: interleukin 1 receptor antagonist; INF: interferon; LN: lupus nephritis; MCP: monocyte chemoattractant protein; MIP: macrophage inflammatory protein; NS: nephrotic syndrome; PMR: polymyalgia rheumatica; PTX3: pentraxine 3; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus; SS: Sjogren’s syndrome; TNF: tumor necrosis factor; TP: thrombocytopenia.