Table 2.
Salivary biomarkers identified in SS.
| Salivary Biomarker | Authors [Ref.] | Subjects | Sample | Used Criteria | Analytical Methods | Findings |
|---|---|---|---|---|---|---|
| β2-microglobulin | Markusse et al. [28] | 39 pSS, 42 non-SS, 41 HC | Stimulated parotid saliva | - | ELISA | 58% of pSS higher levels of mean + 2SD of levels of HC (7%) |
| van der Geest et al. [29] | 29 pSS, 30 HC | Unstimulated and stimulated parotid saliva | - | Radioimmunoassay | Higher in pSS (p < 0.001) | |
| Mogi et al. [31] | pSS, HC, sialoadenitis, diabetes mellitus | Unstimulated whole saliva | - | ELISA | Higher in pSS (p < 0.001) | |
| Ryu et al. [12] | 41 pSS, 15 non-SS sicca, 20 HCs | Stimulated parotid saliva | 2002 AECG | ELISA | Higher 4.3- and 3.7-fold for the low/medium and for the medium/high focus | |
| Hu et al. [15] | 34 pSS, 34 SLE, 34 HC | Stimulated whole saliva | 2002 AECG | ELISA | Higher in pSS (p = 1.25 × 10−10), AUC 0.87 | |
| Baldini et al. [16] | 19 pSS, 10 non-SS sicca SD, 25 sSS, 10 HC | Unstimulated whole saliva | 2002 AECG | ELISA | Higher in pSS than HC (p < 0.001) and RA-sSS (p < 0.05) | |
| Asashima et al. [32] | 71 pSS, 50 sSS, 54 non-SS-CTD, 75 HC | Unstimulated whole saliva | 2002 AECG | ELISA | Higher in pSS (5.3 ± 4.6 mg/L) than non-SS-CTD (2.5 ± 2.1) and HC (1.2 ± 0.7) | |
| Garza-García et al. [33] | 71 pSS | Unstimulated whole saliva | 2012 SICCA | ELISA | Positive correlation with ESSPRI (Kendall’s tau 0.759, 95% CI 0.656–0.837, p < 0.0001) | |
| Lactoferrin | Ryu et al. [12] | 41 pSS, 15 non-SS sicca, 20 HCs | Stimulated parotid saliva | 2002 AECG | ELISA | Higher 3.7- and 3.6-fold in pSS patients with low/medium focus and medium/high focus |
| Markusse et al. [28] | 39 pSS, 42 non SS sicca SD, 41 HC | Stimulated parotid saliva | - | ELISA | 26% of pSS higher levels of mean + 2 SD of levels of HC (0%) | |
| Konttinen et al. [35] | 3 pSS, 5 sSS, 8 HCs | Unstimulated whole saliva | - | radioimmunoassay | Higher in SS (48.92 ± 14.21 μg/mL) than HC (4.03 ± 1.48) | |
| NGAL | Aqrawi et al. [42] | 11 pSS, 11 HCs | Stimulated whole saliva | 2002 AECG | LC-MS | Detected in 8/11 pSS and 2/11 HCs |
| Siglec-5 | Lee et al. [45] | 170 pSS, 43 SLE, 25 HCs | Unstimulated whole saliva | 2012 SICCA | WB, ELISA | Higher in pSS than non-SS (p < 0.001) Negative correlation with salivary flow rate, positive correlation with ocular surface score and serum immunoglobulin G, AUC 0.774 |
| TRIM29 | Sembler-Møller et al. [23] | 24 pSS, 16 non-SS | Unstimulated and stimulated whole saliva | 2016 ACR/EULAR | nano-scale LC-MS | AUC 0.881 for pSS |
| Proinflammatory cytokines | Nguyen et al. [46] | 21 pSS, 19 HCs | Unstimulated whole saliva | 2002 AECG | ELISA | No difference in levels of IL-17 Higher levels of IL-6 in pSS (p < 0.05) |
| Benchabane et al. [47] | 44 pSS, 15 HCs | Stimulated whole saliva | 2002 AECG | ELISA | Higher IL-17A, IL-6, TNF-α, IL-10 in pSS | |
| Kabeerdoss et al. [48] | 43 pSS, 31 HCs | Unstimulated whole saliva | 2002 AECG or 2012 SICCA | ELISA | Higher median levels of sL-selectin, IL-7 in pSS No association between ESSDAI and levels of sL-selectin, IL7 |
|
| Hung et al. [49] | 138 pSS, 100 HCs | Unstimulated whole saliva | 2002 AECG | ELISA | Higher IL-6 (p = 0.012), but not TNF-α, IL-17A, RF-IgA IL-6 correlated with ESR (r = 0.252), IgG (0.248) |
|
| Tvarijonaviciute et al. [60] | 17 SS, 13 HCs, 19 non-SS sicca | Unstimulated whole saliva | 2002 AECG | ELISA | Higher IL-1β vs. HC or non-SS sicca (both p < 0.001) Higher IL-8 vs. HC or non-SS sicca (both p < 0.001) |
|
| Anti-histone, anti-transglutaminase, anti-SSA, and anti-SSB Ab | Hu et al. [50] | 34 pSS, 34 SLE, 34 HCs | Unstimulated whole saliva | 2002 AECG | ELISA | AUC of anti-histone, anti-transglutaminase, anti-SSA, anti-SSB antibody 0.95, 0.87, 0.93, 0.94 |
| Muscarinic type 3 receptor (M3R) | Jayakanthan et al. [52] | 43 pSS, 34 SLE, 42 HCs | Unstimulated whole saliva | 2002 AECG or 2012 SICCA | ELISA | Positive in 55.81, 17.64, 7% of pSS, SLE, HCs Positivity was associated with lower age, shorter disease duration, higher globulin levels |
| Mona et al. [53] | 37 pSS, 26 non SS-sicca | Unstimulated and stimulated whole saliva | 2002 AECG | On-Cell-Western assay | Higher (3.59) in pSS, AUC 0.84 | |
| Tissue-specific antibodies (anti-CA6, SP1 and PSP) | Jin et al. [54] | 137 pSS, 32 SLE-sSS, 127 HCs | Unstimulated whole saliva | 2002 AECG or 2012 SICCA | ELISA | Higher anti-CA6 IgG (p < 0.01), anti-SP1 IgG (p < 0.01), anti-PSP2 IgG (p < 0.05) in pSS than HCs |
| Calprotectin | Jazzar et al. [59] | 51 SS, 14 SS with MALT lymphoma, 18 HCs | Unstimulated whole and parotid saliva | 2002 AECG and 2012 SICCA | ELISA | Higher S100A8/A9 in parotid saliva of SS (743.1 ng/mL) than HC (31.9, p = 0.001) and than SNOX (208.9, p = 0.031) |
| Adiponectin | Tvarijonaviciute et al. [60] | 17 SS, 13 HCs, 19 non-SS sicca | Unstimulated whole saliva | 2002 AECG | ELISA | Higher adiponectin in SS than HC (p = 0.034) and non-SS sicca (p = 0.007) Higher ADA in SS than HC (p = 0.034) and non-SS sicca (p = 0.033) |
pSS, primary Sjogren’s syndrome; AECG, the American-European Consensus Group criteria; SICCA, the American College of Rheumatology/Sjögren’s International Collaborative Clinical Alliance criteria; ACR/EULAR, the American College of Rheumatology/European league against rheumatism classification criteria; NGAL, neutrophil gelatinase-associated lipocalin; siglec, soluble sialic acid-binding immunoglobulin-like lectin; TRIM, tripartite motif-containing protein; CA6, carbonic anhydrase VI; SP, salivary protein; PSP, parotid secretory protein; SLE, systemic lupus erythematosus; HC, healthy controls; ELISA, Enzyme-linked immunosorbent assay; SD, standard deviations; AUC, area under curve; IL, interleukin, TNF, tumor necrosis factor; ESSPRI, The EULAR Sjögren’s syndrome Patient Reported Index; ESSDAI, EULAR Sjögren’s Syndrome Disease Activity Index; sL-selectin, soluble L-selectin; RF, rheumatoid factor; SNOX, sialadenitis, nodular osteoarthritis and xerostomia; ADA, adenosine deaminase.