Volume: 46 Issue: 3
Year: 2026, Page: 171-182, Doi: https://doi.org/10.51248/v46i3.82
Received: July 17, 2026 Accepted: Sept. 21, 2026 Published: Sept. 25, 2026
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by loss of immune tolerance, autoantibody production, immune-complex deposition, and persistent inflammation. Lupus nephritis (LN) is a serious manifestation of SLE, affecting approximately 40–60% of patients and contributing substantially to morbidity and mortality. Conventional biomarkers, including anti-double-stranded DNA antibodies, complement C3/C4, proteinuria, and serum creatinine, incompletely reflect molecular disease activity, while renal biopsy, although the gold standard, is invasive and unsuitable for frequent longitudinal assessment. Extracellular vesicles (EVs) are membrane-enclosed particles that can transport proteins, lipids, messenger RNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and DNA. Their cargo reflects the state of parent cells and participates in immune activation, type I interferon signaling, complement dysregulation, endothelial injury, and renal inflammation. This review synthesizes evidence on EV biology and immunopathogenesis in SLE/LN and critically evaluates EV-associated proteins, miRNAs, and emerging non-coding RNAs as biomarkers. Proteomic and multi-omics approaches increasingly support multi-analyte signatures rather than single biomarkers. Major barriers to translation include heterogeneous isolation methods, incomplete vesicle characterization, small cohorts, variable analytical workflows, limited external validation, and lack of standardized normalization. Future clinical utility will depend on MISEV-aligned workflows, prospective multicentre validation, comparison with established biomarkers, and integration of EV-associated molecular profiles with clinical data and artificial intelligence. EVs therefore represent a promising liquid-biopsy platform, but clinical adoption requires rigorous standardization and demonstration of incremental value over existing tools.
Keywords: Extracellular vesicles; small extracellular vesicles; systemic lupus erythematosus; lupus nephritis; biomarkers
1. Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365(22):2110-21.
2. Kaul A, Gordon C, Crow MK, Touma Z, Urowitz MB, Ruiz-Irastorza G, et al., Systemic lupus erythematosus. Nat Rev Dis Primers. 2016; 2:16039
3. Fanouriakis A, Kostopoulou M, Cheema K, et al., EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024;83:15-29
4. Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):7
5. Rovin BH, Adler SG, Barratt J, et al., KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis. Kidney Int. 2024;105(Suppl 1):S1-S69
6. Welsh JA, Goberdhan DCI, O'Driscoll L, et al., MISEV Consortium. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J Extracell Vesicles. 2024;13(2):e12404
7. Zheng C, Xie L, Qin H, Liu X, Chen X, Lv F, Wang L, Zhu X, Xu J. The Role of Extracellular Vesicles in Systemic Lupus Erythematosus. Front Cell Dev Biol.2022;10:835566. doi:10.3389/fcell.2022.835566
8. Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581-93
9. Shen J, Zhang F, Liu G, et al., Progress of exosome research in systemic lupus erythematosus. Front Immunol. 2022;13:853903
10. Akbar N, Burger D, Bussolati B, Buzás EI, Carney RP, Cho YE, et al., Updating MISEV: When, What, How, and Why? J Extracell Vesicles. 2026;15(2):e70230
11. Lady J. Rios-Serna, María del Mar Rojas-Pelaez, Mildrey Mosquera Escudero, Herney Andres García-Perdomo, Carlos A. Cañas, Extracellular vesicles and their role in Lupus Nephritis: A scoping review; Journal of Translational Autoimmunity; 2026: Volume 12: 100356, ISSN 2589-9090,https://doi.org/10.1016/j.jtauto.2026.100356
12. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977
13. Mathieu M, Martin-Jaular L, Lavieu G, Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9-17
14. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373-83
15. Yáñez-Mó M, Siljander PRM, Andreu Z, et al., Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066
16. Schwarzenbach H, Gahan PB. Exosomes in immune regulation. Adv Clin Chem. 2021;103:123-52
17. Wu Y, Dong HR, Liu LT, Peng ML, Su XL. Advances in the study of exosome-derived miRNAs in the pathogenesis, diagnosis, andtreatment of systemic lupus erythematosus. Lupus. 2023 Nov;32(13):1475-1485. doi: 10.1177/09612033231212280. Epub 2023 Oct 31
18. Almohaimeed HM, Almars AI, Tounsi WA, et al., Exosomes in Autoimmunity: Mediators of Autoantigen Presentation and Targets for Therapeutic Intervention in Autoimmune Diseases. J Clin Immunol. 2025;46(1):3
19. Ricklin D, Reis ES, Mastellos DC, Gros P, Lambris JD. Complement component C3-The “Swiss Army Knife” of innate immunity and host defense. Immunol Rev. 2016;274(1):33-58
20. Karasu E, Eisenhardt SU, Harant J, Huber-Lang M. Extracellular vesicles: Packages sent with complement. Front Immunol. 2018;9:721
21. Fan S, Poetsch A. Proteomic Research of Extracellular Vesicles in Clinical Biofluid. Proteomes. 2023;11(2):18
22. Schey KL, Luther JM, Rose KL. Proteomics characterization of exosome cargo. Methods. 2015;87:75-82
23. Chatzopoulos MK, Fragoulis GE, Samiotaki M, Tektonidou MG, Sfikakis PP, Vetsika EK. Small extracellular vesicle cargo as biomarkers in autoimmune rheumatic diseases: a systematic review. Rheumatol Int. 2025 Sep 1;45(9):211. doi: 10.1007/s00296-025-05953-w
24. Picca A, Guerra F, Calvani R, et al., Extracellular vesicles and damage-associated molecular patterns: A Pandora’s box in health and disease. Front Immunol. 2020;11:601740
25. Salvi V, et al., Exosome-delivered microRNAs promote IFN-α secretion by human plasmacytoid dendritic cells via TLR7. JCI Insight. 2018;3:e98204
26. Zhang N, Dong N, Xie A, Liu W, Khan A, Rui Y, Yang P. Urinary extracellular vesiclemetabolomic profiling reveals a distinct molecular signature for the non-invasive diagnosis of lupus nephritis. Front Immunol. 2026 Feb 17;17:1741455. doi: 10.3389/fimmu.2026.1741455
27. Zhang H, Zheng X, Huang S, Qian L, Wu J, Shi Z, Jia M, Bai Y, Jiang L, Jia S, Zen K, Yuan Y, Liang J, Liang H. Urinary extracellular vesicle RNAs as novel biomarkers for diagnosis and prognosis of lupus nephritis. Clin Kidney J. 2025 Sep 22;18(10):sfaf295. doi: 10.1093/ckj/sfaf295
28. Alves L, Lemos AP, Martins J, da Costa Fonseca S, Gaudio RC, et. al., Podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritis. Sci Rep. 2025 Aug 5;15(1):28630. doi: 10.1038/s41598-025-08236-3
29. Benc K, Tabaka E, Pabian W, Pisarek D, Marek-Bukowiec K, Konieczny A, Banasik M. Urinary Exosomes as Potential Biomarkers for Diagnosis, Disease Activity Assessment, Treatment Monitoring, and Prognosis in Lupus Nephritis. Int J Mol Sci. 2026 Aug 6;27(15):7051. doi: 10.3390/ijms27157051
30. Kaplan MJ, Tsai CY. What’s wrong with neutrophils in lupus? Clin Exp Rheumatol. 2019;37(5):684-93
31. Tang Y, Luo X, Cui H, et al., MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting IRAK1 and TRAF6. Arthritis Rheum. 2009;60(4):1065-75
32. O’Connell RM, Kahn D, Gibson WSJ, et al., MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T-cell development. Immunity. 2010;33(4):607-19
33. Qin W, Chung AC, Huang XR, Meng XM, Hui DS, Yu CM, Sung JJ, Lan HY. TGF-β/Smad3 signaling promotes renal fibrosis by inhibiting miR-29. J Am Soc Nephrol.2011 Aug;22(8):1462-74. doi: 10.1681/ASN.2010121308. Epub 2011 Jul 22
34. Niewold TB. Interferon alpha as a primary pathogenic factor in systemic lupus erythematosus. J Interferon Cytokine Res. 2011;31(12):887-92
35. Querin V, Palazzo L, Fogo AB, Haas M, Jayne DRW, Lightstone L, Rovin BH, Seshan SV, Vaglio A, Parodis I, Bajema IM; Lupus Nephritis Classification Steering Committee. Biomarkers of Lupus Nephritis Histopathology: Where Do We Stand? Arthritis Rheumatol. 2026 Mar;78(3):548-557. doi: 10.1002/art.43427. Epub 2026 Jan 28
Aarti Verma, Vineeta Batra, Jayanand. Extracellular Vesicle Biomarkers in Systemic Lupus Erythematosus and Lupus Nephritis: Emerging Roles in Pathogenesis, Biomarker Development, and Clinical Translation. Biomedicine: 2026, 46(3): 171-182. https://doi.org/10.51248/v46i3.82