Cytokine profiles and their correlation with clinical and blood parameters in rheumatoid arthritis and systemic lupus erythematosus.
Cytokines
Rheumatoid arthritis
Spearman’s correlation
Systemic lupus erythematosus
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 10 2024
08 10 2024
Historique:
received:
22
02
2024
accepted:
09
09
2024
medline:
9
10
2024
pubmed:
9
10
2024
entrez:
8
10
2024
Statut:
epublish
Résumé
The abnormal biological activity of cytokines and their imbalance are implicated in developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Cytokine levels were measured in RA and SLE patients and compared to healthy controls using the Wilcoxon rank sum test and Kruskal-Wallis test. The relationship between cytokine levels and blood and clinical parameters was assessed using Spearman's correlation test. Compared to healthy controls, both RA and SLE patients exhibited elevated levels of GM-CSF, CX3CL1, IFN-α2, IL-12p70, IL-17A, TNF-α, IL-1β, and IFN-γ, which is evidence of their shared inflammatory signature. IL-2 levels were elevated exclusively in RA patients, while MCP-1 and IL-10 were uniquely increased in SLE patients. Notably, TNF-α showed the most significant increase in SLE patients. IL-4 was elevated in SLE patients with nephritis, correlating with IL-6, IL-10, sCD40L, and IL-8, suggesting B cell involvement in lupus nephritis. The negative correlation between CX3CL1 and TNF-α with HDL in RA and SLE respectively, highlights the potential association of these inflammatory markers with cardiovascular risk. These findings underscore the complex cytokine interplay in RA and SLE. CX3CL1 emerges as a potential therapeutic target for RA, while TNF-α and IL-4 show promise as therapeutic targets for SLE.
Identifiants
pubmed: 39379404
doi: 10.1038/s41598-024-72564-z
pii: 10.1038/s41598-024-72564-z
doi:
Substances chimiques
Cytokines
0
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
23475Subventions
Organisme : Ministerio de Ciencia, Tecnología e Innovación
ID : 120389666081
Informations de copyright
© 2024. The Author(s).
Références
Ahmad, R. & Ahsan, H. Dual autoimmune diseases: rheumatoid arthritis with systemic lupus erythematosus and type 1 diabetes mellitus with multiple sclerosis. Rheumatol. Autoimmun. 2, 120–128. https://doi.org/10.1002/rai2.12037 (2022).
doi: 10.1002/rai2.12037
Smolen, J. S. et al. Rheumatoid arthritis. Nat. Rev. Dis. Primers. 4, 1–23. https://doi.org/10.1038/nrdp.2018.1 (2018).
doi: 10.1038/nrdp.2018.1
Vasquez-Canizares, N., Wahezi, D., Putterman, C. & Einstein, A. Diagnostic and prognostic tests in systemic lupus erythematosus. Best Pract. Res. Clin. Rheumatol. 31, 351–363. https://doi.org/10.1016/j.berh.2017.10.002.Diagnostic (2018).
doi: 10.1016/j.berh.2017.10.002.Diagnostic
Fernández-Ávila, D. G., Rincón-Riaño, D. N., Bernal-Macías, S., Dávila, J. M. & Rosselli, D. Prevalencia de la artritis reumatoide en Colombia según información del Sistema Integral de Información de la Protección Social. Rev. Colombiana de Reumatol. 26(2), 83–87. https://doi.org/10.1016/j.rcreu.2019.01.003 (2019).
doi: 10.1016/j.rcreu.2019.01.003
Fernández-Ávila, D. G., Bernal-Macías, S., Rincón-Riaño, D. N., Gutiérrez Dávila, J. M. & Rosselli, D. Prevalence of systemic lupus erythematosus in Colombia: data from the national health registry 2012–2016. Lupus 28, 1273–1278. https://doi.org/10.1177/0961203319864168 (2019).
doi: 10.1177/0961203319864168
pubmed: 31354025
Theofilopoulos, A. N., Kono, D. H. & Baccala, R. The multiple pathways to autoimmunity. Nat. Immunol. 18, 716–724. https://doi.org/10.1038/ni.3731.The (2018).
doi: 10.1038/ni.3731.The
Miller, F. W. The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention. Curr. Opin Immunol. https://doi.org/10.1016/j.coi.2022.102266 (2023).
doi: 10.1016/j.coi.2022.102266
pubmed: 36446151
Anaya, J.-M. & Beltrán, S. The autoimmune tautology revisited. J. Transl. Autoimmun. https://doi.org/10.1016/j.jtauto.2023.100204 (2023).
doi: 10.1016/j.jtauto.2023.100204
pubmed: 38544807
pmcid: 10966307
Smolen, J. S. et al. Rheumatoid arthritis. Nat. Rev. Disease Primers 4, 1–23. https://doi.org/10.1038/nrdp.2018.1 (2018).
doi: 10.1038/nrdp.2018.1
Kaul, A. et al. Systemic lupus erythematosus. Nature Publishing Group 2, 1–22. https://doi.org/10.1038/nrdp.2016.39 (2016).
doi: 10.1038/nrdp.2016.39
Talaat, R. M., Mohamed, S. F., Bassyouni, I. H. & Raouf, A. A. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: correlation with disease activity. Cytokine 72, 146–153. https://doi.org/10.1016/J.CYTO.2014.12.027 (2015).
doi: 10.1016/J.CYTO.2014.12.027
pubmed: 25647269
Yao, S. et al. Genetic ancestry and population differences in levels of inflammatory cytokines in women: Role for evolutionary selection and environmental factors. PLoS Genet https://doi.org/10.1371/journal.pgen.1007368 (2018).
doi: 10.1371/journal.pgen.1007368
pubmed: 30096138
pmcid: 6105014
Slight-Webb, S. et al. Ancestry-based differences in the immune phenotype are associated with lupus activity. JCI Insight https://doi.org/10.1172/jci (2023).
doi: 10.1172/jci
pubmed: 37606045
pmcid: 10543734
Rishishwar, L. et al. Ancestry, admixture and fitness in Colombian genomes. Sci. Rep. https://doi.org/10.1038/srep12376 (2015).
doi: 10.1038/srep12376
pubmed: 26197429
pmcid: 4508918
Kay, J. & Upchurch, K. S. ACR/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatology (Oxford) 51(Suppl), 6. https://doi.org/10.1093/RHEUMATOLOGY/KES279 (2012).
doi: 10.1093/RHEUMATOLOGY/KES279
Prevoo, M. L. L. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 38, 44–48. https://doi.org/10.1002/ART.1780380107 (1995).
doi: 10.1002/ART.1780380107
pubmed: 7818570
Petri, M. et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64, 2677–2686. https://doi.org/10.1002/ART.34473 (2012).
doi: 10.1002/ART.34473
pubmed: 22553077
pmcid: 3409311
Bombardier, C. et al. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35, 630–640. https://doi.org/10.1002/ART.1780350606 (1992).
doi: 10.1002/ART.1780350606
pubmed: 1599520
Gottfried-Blackmore, A. et al. Effects of processing conditions on stability of immune analytes in human blood. Sci. Rep. https://doi.org/10.1038/s41598-020-74274-8 (2020).
doi: 10.1038/s41598-020-74274-8
pubmed: 33060628
pmcid: 7566484
Cacciatore, S., Tenori, L., Luchinat, C., Bennett, P. R. & MacIntyre, D. A. KODAMA: an R package for knowledge discovery and data mining. Bioinformatics 33, 621–623. https://doi.org/10.1093/bioinformatics/btw705 (2017).
doi: 10.1093/bioinformatics/btw705
pubmed: 27993774
Ogle D, Doll J, Wheeler A, Dinno A. FSA: Simple Fisheries Stock Assessment Methods. R package version 0.9.5, 2023.
Kolde R. Pheatmap: Pretty Heatmaps. R package version 1.0.12 2019.
Robin, X. et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinform. 12, 1–8 (2011).
doi: 10.1186/1471-2105-12-77
Cacciatore, S., Luchinat, C. & Tenori, L. Knowledge discovery by accuracy maximization. Proc. Natl. Acad. Sci. USA 111, 5117–5122. https://doi.org/10.1073/pnas.1220873111 (2014).
doi: 10.1073/pnas.1220873111
pubmed: 24706821
pmcid: 3986136
Nanki, T., Imai, T. & Kawai, S. Fractalkine/CX3CL1 in rheumatoid arthritis. Mod. Rheumatol. 27, 392–397. https://doi.org/10.1080/14397595.2016.1213481 (2017).
doi: 10.1080/14397595.2016.1213481
pubmed: 27484962
Chen, Z., Bozec, A., Ramming, A. & Schett, G. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nat. Rev. Rheumatol. 15, 9–17. https://doi.org/10.1038/S41584-018-0109-2 (2018).
doi: 10.1038/S41584-018-0109-2
Andretto, V. et al. Tackling TNF-α in autoinflammatory disorders and autoimmune diseases: from conventional to cutting edge in biologics and RNA- based nanomedicines. Adv. Drug. Deliv. Rev. https://doi.org/10.1016/j.addr.2023.115080 (2023).
doi: 10.1016/j.addr.2023.115080
pubmed: 37660747
Meijer C, Huysen V, Smeenk RTJ, Swaak AJG. Profiles of Cytokines (TNFα and IL-6) and Acute Phase Proteins (CRP and α1AG) related to the Disease Course in Patients with Systemic Lupus Erythematosus Correspondence. n.d.
Singh, R. R. IL-4 and many roads to lupuslike autoimmunity. Clin. Immunol. 108, 73–79. https://doi.org/10.1016/S1521-6616(03)00145-1 (2003).
doi: 10.1016/S1521-6616(03)00145-1
pubmed: 12921752
Anaya, J. M. The autoimmune tautology. A summary of evidence. Joint Bone Spine 84, 251–253. https://doi.org/10.1016/J.JBSPIN.2016.11.012 (2017).
doi: 10.1016/J.JBSPIN.2016.11.012
pubmed: 28017820
Rodríguez-Carrio, J. et al. Circulating endothelial cells and their progenitors in systemic lupus erythematosus and early rheumatoid arthritis patients. Rheumatology 51, 1775–1784. https://doi.org/10.1093/RHEUMATOLOGY/KES152 (2012).
doi: 10.1093/RHEUMATOLOGY/KES152
pubmed: 22753774
Rodríguez-Carrio, J., Alperi-López, M., López, P., Ballina-García, F. J. & Suárez, A. Profiling of B-cell factors and their decoy receptors in rheumatoid arthritis: association with clinical features and treatment outcomes. Front. Immunol. 9, 2351. https://doi.org/10.3389/FIMMU.2018.02351/BIBTEX (2018).
doi: 10.3389/FIMMU.2018.02351/BIBTEX
pubmed: 30369929
pmcid: 6194314
Zhou, H. et al. Elevated circulating T cell subsets and cytokines expression in patients with rheumatoid arthritis. Clin. Rheumatol. 38, 1831–1839. https://doi.org/10.1007/S10067-019-04465-W/FIGURES/4 (2019).
doi: 10.1007/S10067-019-04465-W/FIGURES/4
pubmed: 30809737
Gottenberg, J. E. et al. Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort. Ann. Rheum. Dis. 71, 1243–1248. https://doi.org/10.1136/ANNRHEUMDIS-2011-200975 (2012).
doi: 10.1136/ANNRHEUMDIS-2011-200975
pubmed: 22532637
Li, B. et al. Increased serum interleukin-2 levels are associated with abnormal peripheral blood natural killer cell levels in patients with active rheumatoid arthritis. Mediators Inflamm. https://doi.org/10.1155/2020/6108342 (2020).
doi: 10.1155/2020/6108342
pubmed: 33488293
pmcid: 7785383
Zhou, H. et al. Aberrant T cell subsets and cytokines expression profile in systemic lupus erythematosus. Clin. Rheumatol. 37, 2405–2413. https://doi.org/10.1007/S10067-018-4124-0 (2018).
doi: 10.1007/S10067-018-4124-0
pubmed: 29785672
Willis, R. et al. Clinical associations of proinflammatory cytokines, oxidative biomarkers and vitamin D levels in systemic lupus erythematosus. Lupus 26, 1517–1527. https://doi.org/10.1177/0961203317706557 (2017).
doi: 10.1177/0961203317706557
pubmed: 28467291
pmcid: 5493999
Melamud, M. M. et al. Multiplex analysis of serum cytokine profiles in systemic lupus erythematosus and multiple sclerosis. Int. J. Mol. Sci. https://doi.org/10.3390/ijms232213829 (2022).
doi: 10.3390/ijms232213829
pubmed: 36430309
pmcid: 9695219
López, P., Rodríguez-Carrio, J., Martínez-Zapico, A., Caminal-Montero, L. & Suarez, A. Senescent profile of angiogenic T cells from systemic lupus erythematosus patients. J. Leukoc. Biol. 99, 405–412. https://doi.org/10.1189/jlb.5HI0215-042R (2015).
doi: 10.1189/jlb.5HI0215-042R
pubmed: 26232454
Živković, V. et al. Monocyte chemoattractant protein-1 as a marker of systemic lupus erythematosus: an observational study. Rheumatol. Int. 38, 1003–1008. https://doi.org/10.1007/s00296-017-3888-x (2018).
doi: 10.1007/s00296-017-3888-x
pubmed: 29181621
Chun, H. Y. et al. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol 27, 461–466. https://doi.org/10.1007/S10875-007-9104-0 (2007).
doi: 10.1007/S10875-007-9104-0
pubmed: 17587156
Damiati, L. A., Denetiu, I., Bahlas, S., Damiati, S. & Pushparaj, P. N. Immunoprofiling of cytokines, chemokines, and growth factors in female patients with systemic lupus erythematosus– a pilot study. BMC Immunol. https://doi.org/10.1186/s12865-023-00551-6 (2023).
doi: 10.1186/s12865-023-00551-6
pubmed: 37370001
pmcid: 10303283
Singh, S., Anshita, D. & Ravichandiran, V. MCP-1: function, regulation, and involvement in disease. Int. Immunopharmacol. https://doi.org/10.1016/j.intimp.2021.107598 (2021).
doi: 10.1016/j.intimp.2021.107598
pubmed: 34890999
pmcid: 8563344
Rojas, M. et al. Cytokines and inflammatory mediators in systemic lupus erythematosus. Rheumatology 11, 1–5 (2018).
Hoshino-Negishi, K. et al. Role of anti-fractalkine antibody in suppression of joint destruction by inhibiting migration of osteoclast precursors to the synovium in experimental arthritis. Arthritis Rheumatol. 71, 222–231. https://doi.org/10.1002/art.40688 (2019).
doi: 10.1002/art.40688
pubmed: 30079992
Lai, Y. & Dong, C. Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases. Int. Immunol. 28, 181–188. https://doi.org/10.1093/intimm/dxv063 (2016).
doi: 10.1093/intimm/dxv063
pubmed: 26545932
McInnes, I. B., Buckley, C. D. & Isaacs, J. D. Cytokines in rheumatoid arthritis — shaping the immunological landscape. Nat. Rev. Rheumatol. 12, 63–68. https://doi.org/10.1038/nrrheum.2015.171 (2015).
doi: 10.1038/nrrheum.2015.171
pubmed: 26656659
Idborg, H. & Oke, V. Cytokines as biomarkers in systemic lupus erythematosus: value for diagnosis and drug. Therapy https://doi.org/10.3390/ijms222111327 (2021).
doi: 10.3390/ijms222111327
Aringer, M. & Smolen, J. S. Therapeutic blockade of TNF in patients with SLE-Promising or crazy?. Autoimmun. Rev. 11, 321–325. https://doi.org/10.1016/j.autrev.2011.05.001 (2012).
doi: 10.1016/j.autrev.2011.05.001
pubmed: 21619949
Bonacina, F., Pirillo, A., Catapano, A. L. & Norata, G. D. Hdl in immune-inflammatory responses: implications beyond cardiovascular diseases. Cells https://doi.org/10.3390/cells10051061 (2021).
doi: 10.3390/cells10051061
pubmed: 33947039
pmcid: 8146776
Barter, P. J. et al. Antiinflammatory properties of HDL. Circ. Res. 95, 764–772. https://doi.org/10.1161/01.RES.0000146094.59640.13 (2004).
doi: 10.1161/01.RES.0000146094.59640.13
pubmed: 15486323
Kim, S. Y. et al. High-density lipoprotein in lupus: disease biomarkers and potential therapeutic strategy. Arthritis Rheumatol. 72, 20–30. https://doi.org/10.1002/art.41059 (2020).
doi: 10.1002/art.41059
pubmed: 31350818
McMahon, M. et al. Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 54, 2541–2549. https://doi.org/10.1002/art.21976 (2006).
doi: 10.1002/art.21976
pubmed: 16868975
Tanaka, Y. et al. Emerging role of fractalkine in the treatment of rheumatic diseases. Immunotargets Ther. 9, 241–253. https://doi.org/10.2147/ITT.S277991 (2020).
doi: 10.2147/ITT.S277991
pubmed: 33178636
pmcid: 7649223
Sethi, J. K. & Hotamisligil, G. S. Metabolic messengers: tumour necrosis factor. Nat. Metab. 3, 1302–1312. https://doi.org/10.1038/s42255-021-00470-z (2021).
doi: 10.1038/s42255-021-00470-z
pubmed: 34650277
Field, F. J., Watt, K. & Mathur, S. N. TNF-α decreases ABCA1 expression and attenuates HDL cholesterol efflux in the human intestinal cell line Caco-2. J. Lipid Res. 51, 1407–1415. https://doi.org/10.1194/jlr.M002410 (2010).
doi: 10.1194/jlr.M002410
pubmed: 20103810
pmcid: 3035503
McInnes, I. B. & Schett, G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat. Rev. Immunol. 7, 429–442. https://doi.org/10.1038/nri2094 (2007).
doi: 10.1038/nri2094
pubmed: 17525752