Table 2.

Comparative proteomic analysis of saliva, salivary gland tissue and/or blood from patients with pSS patients with RA, SLE, systemic sclerosis, mixed connective tissue disease (MCTD) and poly- and dermatomyositis (1.2).

Author (year)	No. of subjects	Materials and methods	Findings
Peluso G, et al., 2007 (26)	9 pSS 3 RA-sSS 3 SSc-sSS 3 SLE-sSS 9 HC	UWS HPLC-ESI-MS	In 6 of the pSS patients, saliva was collected at 30 minutes, 60 minutes, and 24 hours after taking 5 mg of pilocarpine. Before pilocarpine, 60% of salivary proteins in samples from pSS patients were not identifiable or showed lower levels than those in controls. After 30–60 minutes following pilocarpine treatment, 1/3 of the less represented proteins was found in a similar percentage in pSS and controls. Almost all of the proteins that were detectable at lower levels in pSS compared to controls reached levels similar to those in controls at 30–60 minutes after pilocarpine. The parotid gland proteins had the best response to pilocarpine. PSS patients were characterized by higher α-defensin 1 levels and presence of β-defensin 2. sSS patients showed an intermediate protein profile between that of the pSS patients and HC.
Baldini C, et al., 2011 (28)	59 pSS 40 sSS 61 HC 20 non-pSS, sicca	UWS	15 differently expressed proteins were identified in pSS samples with respect to HC, non-SS sicca, SSc-sSS and RA-sSS. pSS vs. HC: ↑ S100A9, B2M, epidermal fatty acid binding protein (E-FABP), psoriasin (S100A7), immunoglobulin k light chain (IGKC) and α-enolase. ↓ AMY1A, carbonic anhydrase VI (CA6), glyceraldehydes-3-phosphate dehydrogenase (G3PDH), cystatin SN precursor protein (CST1), prolactin-inducible protein precursor (PIP), short palate, lung and nasal epithelium (SPLUNC-2). pSS vs. non-pSS sicca: ↑ PIP, SPLUNC-2 G3PDH, AMY1A, CA6. pSS vs. RA-sSS: ↑ lipocalin. ↓ rheumatoid factor D3 light chain. pSS vs. SSc-sSS: ↓ cystatin.
Li Y, et al., 2014 (50)	60 pSS 50 SLE 50 RA 51 HC	Serum MALDI-TOF-MS	100 differential M/Z peaks associated with pSS were identified (18 were ↑ in pSS). The m/z peaks at 8,133.85, 11,972.8, 2,220.81, and 4,837.66 were used to establish a diagnostic model for pSS which could distinguish pSS from non-pSS controls with a sensitivity of 77.1 % and a specificity of 85.5 %. Its efficacy was confirmed in a blinded testing set with a sensitivity and specificity of 95.5% and 88%, respectively.
Delaleu N, et al., 2015 (36)	48 pSS 12 RA 12 HC	UWS 187-plex capture antibody-based assay	Based on a 187-plex antibody-based assay, 61 and 55 proteins were differentially expressed in pSS and RA, compared to HC. All proteins were upregulated in pSS patients, except FGF-4. Based on 4-plex and 6-plex biomarker signatures, which both included IL-4, IL-5 and clusterin, achieved accurate prediction of an individual’s group membership for at least 94% of cases.
Bosello S, et al., 2016 (39)	9 pSS 7 SLE 7 RA 7 sSS/SSc 7 sSS/SLE 7 sSS/RA 7 SSc 10 HC	UWS, MSGB HPLC-ESI-MS (UWS), immunostaining (MSGB)	↑ levels of Tβ4 in pSS compared to other subgroups. Tβ10 detectable in 66,7% of pSS subjects and 42,9% of sSS/SSc patients. Tβ4 sulfoxide detectable in 44,4% of pSS patients and 42,9% of sSS/SSc patients. Tβ4 and Tβ10 not detectable in non-ss associated patients and HC. All patients had immunoreactivity for Tβ10. Tβ4 immunoreactivity was absent in pSS and sSS/RA-patients, but present in sSS/SSc and sSS/SLE-patients. In pSS, salivary Tβ expression was generally overexpressed.
Ohlsson M et al, 2021 (59)	73 pSS (AECG) 39 SLE 46 RA 82 ANCA-SV 77 HC	Serum 393-plex antibody microarray	All 393 antibodies could discriminate between IRD’s from HC with an AUC of 0.94. Based on a panel consisting of the 40 best-performing antibodies IRD could be discriminated from HC with an AUC of 0.93. The IRD could also be discriminated from each other with AUC levels ranging from 0.79 to 0.96. 77 analytes, targeted by 114 antibodies were differentially expressed in IRD compared to HC: 326 antibodies targeting 160 analytes for SV, 207 antibodies targeting 127 analytes for SS, 127 antibodies targeting 85 analytes for SLE and 114 antibodies targeting 81 analytes for RA. ↑ immunoregulatory analytes included apolipoprotein, A1, IL-6, IL-12, TNF-alfa, IL-16, osteopontin. Antibodies targeting C3, IL-4, VEGF, SPDLY-1 etc. were ↓. Among the top 25 antibodies, most of the analytes were ↑ in SLE, RA and SS (15, 21 and 25, respectively). The majority of analytes (n = 23) were ↓ in ANCA-SV.
Thiagarajan D et al, 2020 (63)	324 pSS 374 SLE 354 RA 77 MCTD 65 PAPs 118 UCTD, 331 SSc 515 HC	Serum, PBMC ELISA, LC-MS	Significantly lower IgM anti-PC but not anti-MDA was seen in MCTD compared to HC. No significant difference in levels of anti-PC nor anti-MDA was identified between disease groups, but low levels of IgM were more prevalent in MCTD, SLE, SjS, SSc and UCTD, more for anti-PC than anti-MDA.

Arrow up: upregulated.

Arrow down: downregulated.