Peripheral Classic and Intermediate Monocyte Subsets as Immune Biomarkers of Systemic Lupus Erythematosus Disease Activity

Amaylia Oehadian, Mohammad Ghozali, Sutiadi Kusuma, Lusi Mersiana, Nadia Gita Ghassani, Fransisca Fransisca, Yitzchak Millenard Sigilipu, Andini Kartikasari, Laniyati Hamijoyo

Abstract


Background: Monocytes are evolutionarily preserved innate immune cells that play essential roles in immune response regulation. Three activated monocyte subsets—classical (CD14++CD16–), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++)—are associated with systemic lupus erythematosus (SLE) progression. This study aims to determine the association of monocyte subsets with SLE disease activity. Methods: A cross-sectional study involving 25 patients with SLE was conducted. Blood samples were collected, and monocyte subsets were identified using flow cytometry. Patients were grouped by disease activity using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) into inactive (SLEDAI-2K ≤ 4) and active (SLEDAI-2K > 4). The cutoff for monocyte subsets was determined using Receiver Operating Characteristic (ROC) analysis. Results: Nine active and 16 inactive subjects were identified. Compared with individuals without active disease, individuals with active disease had significantly lower mean classical monocyte subsets (71.9% vs 88%, p = 0.008), and higher median intermediate monocytes (29.1% vs 11.1%, p = 0.019). The median nonclassical monocyte subsets were not significantly different between the two groups. The cutoff for classical monocytes in active disease was ≤72.2%, AUC = 0.788, p = 0.021, with 66.7% sensitivity and 87.5% specificity; for intermediate monocytes, it was >22.3%, AUC = 0.788, p = 0.014, with 66.7% sensitivity and 100% specificity. Conclusion: Classical and intermediate monocytes could be considered as immune cellular markers for identifying active SLE.


Keywords


Monocytes Subset; SLE; Classical Monocytes; Intermediate Monocytes; Disease Activity

References


Jin Z, Fan W, Jensen MA, Dorschner JM, Bonadurer GF, Vsetecka DM, et al. Single-cell gene expression patterns in lupus monocytes independently indicate disease activity, interferon and therapy. Lupus Science & Medicine. 2017;4(1):e000202.

Suszek D, Górak A, Majdan M. Differential approach to peripheral blood cell ratios in patients with systemic lupus erythematosus and various manifestations. Rheumatology International. 2020;40(10):1625-9.

Ma W-T, Gao F, Gu K, Chen D-K. The role of monocytes and macrophages in autoimmune diseases: a comprehensive review. Frontiers in immunology. 2019;10:1140.

Hirose S, Lin Q, Ohtsuji M, Nishimura H, Verbeek JS. Monocyte subsets involved in the development of systemic lupus erythematosus and rheumatoid arthritis. International immunology. 2019;31(11):687-96.

Zhu H, Hu F, Sun X, Zhang X, Zhu L, Liu X, et al. CD16+ monocyte subset was enriched and functionally exacerbated in driving T-cell activation and B-cell response in systemic lupus erythematosus. Frontiers in immunology. 2016;7:512.

Wong KL, Yeap WH, Tai JJY, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunologic research. 2012;53:41-57.

Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nature reviews immunology. 2005;5(12):953-64.

Yoshimoto K, Suzuki K, Takei E, Ikeda Y, Takeuchi T. Elevated expression of BAFF receptor, BR3, on monocytes correlates with B cell activation and clinical features of patients with primary Sjögren’s syndrome. Arthritis Research & Therapy. 2020;22(1):1-10.

Chen P-M, Tsokos GC. The role of CD8+ T-cell systemic lupus erythematosus pathogenesis: an update. Current opinion in rheumatology. 2021;33(6):586.

Pan L, Lu M-P, Wang J-H, Xu M, Yang S-R. Immunological pathogenesis and treatment of systemic lupus erythematosus. World Journal of Pediatrics. 2020;16:19-30.

Kapellos TS, Bonaguro L, Gemünd I, Reusch N, Saglam A, Hinkley ER, et al. Human monocyte subsets and phenotypes in major chronic inflammatory diseases. Frontiers in immunology. 2019;10:2035.

Miyagawa F, Tagaya Y, Ozato K, Horie K, Asada H. Inflammatory monocyte-derived dendritic cells mediate autoimmunity in murine model of systemic lupus erythematosus. Journal of Translational Autoimmunity. 2020;3:100060.

Oke V, Gunnarsson I, Dorschner J, Eketjäll S, Zickert A, Niewold TB, et al. High levels of circulating interferons type I, type II and type III associate with distinct clinical features of active systemic lupus erythematosus. Arthritis research & therapy. 2019;21:1-11.

Cros J, Cagnard N, Woollard K, Patey N, Zhang S-Y, Senechal B, et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity. 2010;33(3):375-86.

Burbano C, Vasquez G, Rojas M. Modulatory effects of CD14+ CD16++ monocytes on CD14++ CD16− monocytes: a possible explanation of monocyte alterations in systemic lupus erythematosus. Arthritis & rheumatology. 2014;66(12):3371-81.

Barrera García A, Gómez-Puerta JA, Arias LF, Burbano C, Restrepo M, Vanegas AL, et al. Infiltrating CD16+ are associated with a reduction in peripheral CD14+ CD16++ monocytes and severe forms of lupus nephritis. Autoimmune Diseases. 2016;2016.

Sümegi A, Antal-Szalmás P, Aleksza M, Kovács I, Sipka S, Zeher M, et al. Glucocorticosteroid therapy decreases CD14-expression and CD14-mediated LPS-binding and activation of monocytes in patients suffering from systemic lupus erythematosus. Clinical immunology. 2005;117(3):271-9.

Jha A, Joseph J, Prabhu SB, Chaudhary A, Yadav B, Mathew J. Utility of peripheral blood monocyte subsets, circulating immune complexes and serum cytokines in assessment of SLE activity: an observational, cross-sectional study. Clinical Rheumatology. 2024;43(1):209-17.

Cormican S, Griffin MD. Human monocyte subset distinctions and function: insights from gene expression analysis. Frontiers in immunology. 2020;11:1070.

Ożańska A, Szymczak D, Rybka J. Pattern of human monocyte subpopulations in health and disease. Scandinavian journal of immunology. 2020;92(1):e12883.

Rogacev KS, Zawada AM, Hundsdorfer J, Achenbach M, Held G, Fliser D, et al. Immunosuppression and monocyte subsets. Nephrology Dialysis Transplantation. 2015;30(1):143-53.

Azeez SH. Impact of Cyclosporine A on white blood cell counts and some physiological parameters in renal transplanted patients: A case control study. International Journal of Medical Investigation. 2021;10(1):111-9.

Sutton EJ, Davidson JE, Bruce IN, editors. The systemic lupus international collaborating clinics (SLICC) damage index: a systematic literature review. Seminars in arthritis and rheumatism; 2013: Elsevier.

Becker-Merok A, Nossent HC. Damage accumulation in systemic lupus erythematosus and its relation to disease activity and mortality. The Journal of Rheumatology. 2006;33(8):1570-7.


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