Tear Cytokine Levels in Sicca Syndrome-Related Dry Eye: A Meta-Analysis
Abstract
:1. Introduction
2. Methods
2.1. Inclusion and Exclusion Criteria
2.2. Search Strategy
2.3. Study Selection
2.4. Data Extraction
2.5. Risk of Bias and Quality Assessment
2.6. Data Analysis
3. Results
3.1. Search and Selection Process
3.2. Characteristics of Included Studies
3.3. Quality Assessments and Risk of Bias
3.4. Meta-Analysis
3.4.1. IFN-γ
3.4.2. IL-10
3.4.3. IL-12P70
3.4.4. IL-17
3.4.5. IL-1α
3.4.6. IL-1β
3.4.7. IL-1 Ra
3.4.8. IL-2
3.4.9. IL-21
3.4.10. IL-22
3.4.11. IL-23
3.4.12. IL-4
3.4.13. IL-6
3.4.14. IL-8
3.4.15. TNF-α
3.5. Results of Individual Studies
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study ID | Study Design | Study Groups | Age | Female | Type of Sample | Classification Criteria | Sampling Method | Analytical Method | Assessed Biomarkers | Findings |
---|---|---|---|---|---|---|---|---|---|---|
Tishler et al., 1998 [12] | Case-control | SS (n = 12) | 55.3 ± 6.3 | 10 (83.33%) | Tears and serum | Vitali et al., 1993 [13] | Capillary Glass Micropipette | ELISA | IL-6 | IL-6 was elevated in tear samples of SS (p < 0.05); however, no significant change detected in serum |
HCT (n = 12) | 60.1 ± 9.9 | 8 (66.67%) | ||||||||
HCT (n = 10) | 26 ± 3.8 | 9 (90%) | ||||||||
Solomon et al., 2001 [14] | Case-control | MGD (n = 13) | 55 ± 16.3 | 7 (53.85%) | Tears and Conjunctival Biopsy | Fox et al., 1986 [11] | Polyester wick | ELISA | IL-1α, IL-1Ra and IL-1β (Precursor and mature forms) | IL-1α and mature IL-1β were elevated in SS. Precursor IL-1β was decreased in SS. IL-1Ra showed no significant change. |
SS (n = 9) | 68 ± 9.1 | 8 (88.89%) | ||||||||
HCT (n = 17) | 37.76 ± 10.13 | 10 (58.82%) | ||||||||
Yoon et al., 2007 [15] | Case-control | SS (n = 8) | 43.63 ± 13.61 | 7 (87.5%) | Tears, serum, Conjunctival Biopsy, and Conjunctival Impression | AECG [6] | Capillary glass tube | ELISA, IHC, Flow cytometry | IL-6 and TNF-α | IL-6 was higher in the SS group compared to the other groups. TNF-α levels were higher in the SS group compared to HCT but not DED. |
DED (n = 10) | 42 ± 9.75 | 8 (80%) | ||||||||
HCT (n = 14) | 40.43 ± 9.47 | 10 (71.42%) | ||||||||
Yoon et al., 2010 [16] | Case-control | SS (n = 16) | 49.9 ± 14.6 | 14 (87.5%) | Tears and Conjunctival Biopsy | AECG [6] | Capillary glass tube or micropipette | ELISA, IHC, Flow cytometry | CXCL9, CXCL10 and CXCL11 | CXCL9, 10, and 11 were elevated in SS in comparison to HCT and DED. |
DED (n = 17) | 47.3 ± 17.8 | 13 (76.47%) | ||||||||
HCT (n = 15) | 43.0 ± 14.9 | 11 (73.33%) | ||||||||
Chung et al., 2012 [17] | Case-control | Mi-KCS-pSS (n = 60) | 51.9 ± 11.7 | 59 (98.33%) | Tears | AECG [6] | Tear strips | ELISA | IL-17 | IL-17 in the MS-KCS group was elevated compared to Mi-KCS group for both total SS and sSS. |
MS-KCS-pSS (n = 46) | 53.4 ± 11.8 | 46 (100%) | ||||||||
Mi-KCS-sSS (n = 5) | 54.5 ± 13.5 | 5 (100%) | ||||||||
MS-KCS-sSS (n = 10) | 46.8 ± 12.5 | 10 (100%) | ||||||||
Villani et al., 2013 [18] | Case-control | RA SS (n = 12) | 51.4 ± 6.1 | 12 (100%) | Tears | ACR/EULAR [7] and AECG [6] | Polyurethane absorbent mini-sponge | ELISA | IL-1α, IL-6, IL-8, and TNF-α | No difference was detected between sSS/RA and RA groups. For sSS/RA group IL-1α and IL-6 were decreased after treatment (p < 0.01), while IL-8 and TNF-α did not show significant changes |
RA non-SS (n = 12) | 48.8 ± 7.4 | 10 (83%) | ||||||||
Lee et al., 2013 [19] | Case-control | SS (n = 24) | 55.9 ± 9.96 | 24 (100%) | Tears | AECG [6] | Capillary glass micropipette | Multiplex bead assay | IL-2, IL-4, IL-6, IL-10 IL-17, IFN-γ, and TNF-α | IL-17, IL-6, IL-4, and TNF-α were elevated in SS compared to DED and HCT. IL-2 was elevated in SS compared to DED. IL-10 was elevated in SS compared to HCT |
DED (n = 25) | 55.4 ± 12.44 | 25 (100%) | ||||||||
HCT (n = 21) | 52.8 ± 13.19 | 21 (100%) | ||||||||
Tan et al., 2014 [20] | Case-control | Non-SS (n = 20) | 50.5 ± 4.6 | 15 (75%) | Tears | Lemp, 1995 [10] | Capillary glass micropipette | ELISA | IL-17 and IL-22 | IL-17 and IL-22 were elevated in the SS group compared to HCT and non-SS patients. |
SS (n = 20) | 52.5 ± 8.1 | 11 (55%) | ||||||||
HCT (n = 20) | 54.2 ± 7.3 | 6 (30%) | ||||||||
Lim et al., 2015 [21] | Prospective study | SS (n = 30) | 57.3 ± 9.1 | 30 (100%) | Tears and Conjunctival Impression | AECG [6] | Capillary glass micropipette | Cytometric bead array and PCR | IL-21 | IL-21 levels were elevated in pSS compared to DED and HCT. |
DED (n = 30) | 58.4 ± 10.1 | 30 (100%) | ||||||||
HCT (n = 20) | 54.2 ± 12.4 | 20 (100%) | ||||||||
Liu et al., 2017 [22] | Case-control | SS (n = 15) | 66.75± 9.38 | 15 (100%) | Tears and Conjunctival Impression | AECG [6] | Capillary glass micropipette | Multiplex bead assay and PCR | IL-17, IL-6, and IL-23 | IL-17 and IL-6 were elevated in the SS group compared to DED and HCT. IL-23 was elevated in the SS group compared to HCT. |
DED (n = 15) | 64.00± 11.00 | 15 (100%) | ||||||||
HCT (n = 15) | 64.37± 8.34 | 15 (100%) | ||||||||
Hernández-Ruiz et al., 2018 [23] | Case-control | SS (n = 28) | 51.1 ± 11.09 | 27 (96.4%) | Tears and Saliva | AECG [6] | Tear strips | ELISA | CXCL17 | CXCL17 was elevated in the SS group. Saliva results showed similar levels |
HCT (n = 28) | 28 (100%) | |||||||||
Luo et al., 2018 [24] | Case-control | SS (n = 30) | 53.5 ± 9.2 | 30 (100%) | Tears and Serum | Lemp, 1995 [10] | Capillary glass tube | ELISA | IL-33, IL-4, IL-5, IFN-γ, IL-10, IL-17, and TGF-β | IL-4 and IL-5 were elevated in the SS group compared to HCT and non-SS. IL-33 was elevated in the SS group compared to non-SS. |
Non-SS (n = 30) | 51.6 ± 8.3 | 30 (100%) | ||||||||
HCT (n = 30) | 50.6 ± 6.7 | 30 (100%) | ||||||||
Zhao et al., 2018 [25] | Prospective study | SS (n = 20) | NA | NA | Tears | ACR [9] | Capillary glass tube | Luminex assay and ELISA | TNF-α, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12P70, IL-13, IFN-γ, EGF and MIP-1α | TNF-α, IL-6, IL-8, and IL-12P70 were elevated in all patient groups compared to HCT. IL-8 and TNF-α were also elevated in SS-ATD compared to the other diseased groups |
Non-SS (n = 20) | ||||||||||
MGD (n = 15) | ||||||||||
HCT (n = 15) | ||||||||||
Chen et al., 2019 [26] | Case-control | SS (n = 29) | 56.8 ± 13.0 | 29 (100%) | Tears and saliva | AECG [6] | Tear strips | Luminex assay | IL-1RA, IL-2, IL-4, IL-17A, IFN-γ, MIP-1b, L-8, IL-12p70, and IP-10 | IL-1RA, IL-2, IL-4, IL-17A, IFN-γ, and MIP-1b were elevated in the SS group compared to DED and HCT. L-8, IL-12p70, and IP-10 were elevated in the SS group compared to HCT. Salivary levels of IP-10 and MIP-1a were elevated in the SS group compared to DED and HCT |
DED (n = 20) | 51.7 ± 10.6 | 20 (100%) | ||||||||
HCT (n = 17) | 45.4 ± 10.9 | 17 (100%) | ||||||||
Akpek et al., 2020 [27] | Prospective study | SS (n = 21) | 63.3 ± 10.1 | 16 (76.2%) | Tears | ACR [9] | Capillary glass tube | Luminex assay | TNF-α, IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, and IL-17A. | IL-8 was elevated in SS compared to HCT and DED. Among all groups IL-6, IL-12p70 and IL-8 were elevated. |
DED (n = 20) | 62.6 ± 7.7 | 17 (85.0%) | ||||||||
HCT (n = 21) | 60.2 ± 5.6 | 14 (66.7%) | ||||||||
Peng et al., 2021 [28] | Case-control | DED (n = 13) | 35.2 ± 11.7 | 10 (76.9%) | Tears | SIT <10, TBUT <10, and anti-dsDNA or anti-Smith antibodies negative | Capillary glass tube | Luminex assay | IL-1β, IL-2, IL-4, IFN-γ, IL 6, IL-8, IL-17F, TNF-α, IL-21, IL-22, and IL-23 | TNF-α and IL-6 were elevated in SS compared to HCT. IL-8 and IL-21 were elevated in SS compared to HCT and DED. IL-23 was decreased in SS compared to HCT. IFN-γ, IL-2, and IL-4 were decreased in SS compared to HCT and DED. |
SLE (n = 17) | 34.1 ± 9.3 | 16 (94.1%) | ||||||||
SS (n = 18) | 41.6± 12.6 | 15 (83.3%) | ||||||||
HCT (n = 30) | 33.7 ± 9.6 | 15 (50%) | ||||||||
Hernández-Molina et al., 2022 [29] | Case-control | SS (n = 21) | NA | 19 (90.4%) | Tears | ACR/EULAR [7] | Tear strips | Luminex assay | CCL2, CXCL8, and CXCL10 | CXCL10 and CCL2 were decreased in the SS group, while CXCL8 was similar. |
HCT (n = 21) | NA | 21 (100%) |
Study ID | Selection | Comparability | Exposure | Total | |||||
---|---|---|---|---|---|---|---|---|---|
Is the Case Definition Adequate? | Representativeness of the Cases | Selection of Controls | Definition of Controls | Comparability of Cases and Controls on the Basis of the Design or Analysis | Ascertainment of Exposure | Same Method of Ascertainment for Cases and Controls | Non-Response Rate | ||
Tishler et al., 1998 [12] | * | * | * | ** | * | * | * | 8 | |
Solomon et al., 2001 [14] | * | * | * | * | * | * | * | * | 8 |
Yoon et al., 2007 [15] | * | * | * | * | * | * | * | 7 | |
Yoon et al., 2010 [16] | * | * | * | * | * | * | * | 7 | |
Chung et al., 2012 [17] | * | * | * | * | ** | * | * | * | 9 |
Villani et al., 2013 [18] | * | * | * | * | * | * | * | * | 8 |
Lee et al., 2013 [19] | * | * | ** | * | * | * | 7 | ||
Tan et al., 2014 [20] | * | * | * | * | * | * | * | * | 8 |
Lim et al., 2015 [21] | * | * | ** | * | * | * | 7 | ||
Liu et al., 2017 [22] | * | * | * | * | * | 5 | |||
Hernández-Ruiz et al., 2018 [23] | * | * | * | * | * | * | * | * | 8 |
Luo et al., 2018 [24] | * | * | ** | * | * | * | 7 | ||
Zhao et al., 2018 [25] | * | * | * | ** | * | * | * | 8 | |
Chen et al., 2019 [26] | * | * | * | * | ** | * | * | * | 9 |
Akpek et al., 2020 [27] | * | * | * | * | * | * | * | * | 8 |
Peng et al., 2021 [28] | * | * | * | * | * | * | * | * | 8 |
Hernández-Molina et al., 2022 [29] | * | * | * | * | * | * | * | * | 8 |
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Aljohani, S.; Jazzar, A. Tear Cytokine Levels in Sicca Syndrome-Related Dry Eye: A Meta-Analysis. Diagnostics 2023, 13, 2184. https://doi.org/10.3390/diagnostics13132184
Aljohani S, Jazzar A. Tear Cytokine Levels in Sicca Syndrome-Related Dry Eye: A Meta-Analysis. Diagnostics. 2023; 13(13):2184. https://doi.org/10.3390/diagnostics13132184
Chicago/Turabian StyleAljohani, Suad, and Ahoud Jazzar. 2023. "Tear Cytokine Levels in Sicca Syndrome-Related Dry Eye: A Meta-Analysis" Diagnostics 13, no. 13: 2184. https://doi.org/10.3390/diagnostics13132184