Document Type : Original Article
Authors
- Zahra Mirfeizi 1
- Sara Samadi 2
- Asal Sadat Azami 1
- Farzaneh Sharifipour 3
- Hasan Mehrad-Majd 4, 5
- Katayoun Samadi 6
- Zhaleh Sahriati Sarabi 1
1 Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
2 Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3 Kidney Transplantation Complications Research Center, Mashhad University of Medical Science, Mashhad, Iran
4 Clinical Research Development Unit, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
5 Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
6 Department of Internal Medicine, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
Abstract
Background: Kidney involvement is prevalent in systemic lupus erythematosus (SLE) and is the leading cause of disability and death. Colony-stimulating factor-1 (CSF-1) may be involved in the development of lupus nephritis (LN). This study aimed to evaluate serum CSF-1 levels in SLE patients with and without proteinuria and its correlation with the value of proteinuria.
Methods: A total of 75 subjects including 25 newly diagnosed SLE cases without renal involvement evidence, 25 new SLE with biopsy-proven LN, and also, 25 healthy controls were included in the study. Serum CSF-1 level was measured in all participants using a human CSF-1 ELISA kit.
Results: Analysis of variance (ANOVA) and post hoc analysis demonstrated significant differences between the three groups including healthy individuals, and SLE subjects with and without nephritis (P=0.006). The mean values of CSF-1 levels were increased among both participants without LN and patients with LN, compared to healthy individuals. However, a statistically significant greater mean concentration of CSF-1 was detected in individuals with LN compared to the healthy group (P=0.004). No significant statistical correlation was found between CSF-1 and 24-hour urine protein. Furthermore, when comparing the activity of SLE, a notable distinction was observed in the SLE disease activity index (SLEDAI) values between individuals with and without proteinuria (P<0.0001).
Conclusion: An upward trend in average CSF-1 levels was observed among both patients with and without LN, in comparison to healthy individuals. Significantly enhanced concentrations of CSF-1 were found in subjects with LN compared to healthy individuals.
Keywords
Main Subjects
- Crow MK. Pathogenesis of systemic lupus erythematosus: risks, mechanisms and therapeutic targets. Ann Rheum Dis. 2023;82(8):999-1014. doi: 10.1136/ard-2022-223741.
- Bhargava R, Li H, Tsokos GC. Pathogenesis of lupus nephritis: the contribution of immune and kidney resident cells. Curr Opin Rheumatol. 2023;35(2):107-16. doi: 10.1097/ bor.0000000000000887.
- Menke J, Rabacal WA, Byrne KT, Iwata Y, Schwartz MM, Stanley ER, et al. Circulating CSF-1 promotes monocyte and macrophage phenotypes that enhance lupus nephritis. J Am Soc Nephrol. 2009;20(12):2581-92. doi: 10.1681/ asn.2009050499.
- Sharifipour F, Zeraati A, Sahebari M, Hatef M, Naghibi M, Rezaieyazdi Z, et al. Association of urinary lipocalin-2 with lupus nephritis. Iran J Basic Med Sci. 2013;16(9):1011-5.
- Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):7. doi: 10.1038/s41572-019-0141-9.
- Musavi ES, Mirfeizi Z, Mehrad-Majd H, Mousavinik S, Samadi K, Zeraati A, et al. The relationship between serum VCAM-1 level and lupus nephritis in patients with systemic lupus erythematosus. J Nephropathol. 2020;10:e16073. doi: 10.34172/jnp.2022.16073.
- Yadav S, Priya A, Borade DR, Agrawal-Rajput R. Macrophage subsets and their role: co-relation with colony-stimulating factor-1 receptor and clinical relevance. Immunol Res. 2023;71(2):130-52. doi: 10.1007/s12026-022-09330-8.
- Menke J, Amann K, Cavagna L, Blettner M, Weinmann A, Schwarting A, et al. Colony-stimulating factor-1: a potential biomarker for lupus nephritis. J Am Soc Nephrol. 2015;26(2):379-89. doi: 10.1681/asn.2013121356.
- Liao W, He XJ, Zhang W, Chen YL, Yang J, Xiang W, et al. MiR-145 participates in the development of lupus nephritis by targeting CSF1 to regulate the JAK/STAT signaling pathway. Cytokine. 2022;154:155877. doi: 10.1016/j. cyto.2022.155877.
- Aguirre-Valencia D, Ríos-Serna LJ, Posso-Osorio I, NaranjoEscobar J, López D, Bedoya-Joaqui V, et al. Expression of BAFF, APRIL, and cognate receptor genes in lupus nephritis and potential use as urinary biomarkers. J Transl Autoimmun. 2020;3:100027. doi: 10.1016/j.jtauto.2019.100027.
- Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-86. doi: 10.1002/art.34473.
- Markowitz GS, D’Agati VD. The ISN/RPS 2003 classification of lupus nephritis: an assessment at 3 years. Kidney Int. 2007;71(6):491-5. doi: 10.1038/sj.ki.5002118.
- Adhya Z, Borozdenkova S, Karim MY. The role of cytokines as biomarkers in systemic lupus erythematosus and lupus nephritis. Nephrol Dial Transplant. 2011;26(10):3273-80. doi: 10.1093/ndt/gfq860.
- Tian S, Li J, Wang L, Liu T, Liu H, Cheng G, et al. Urinary levels of RANTES and M-CSF are predictors of lupus nephritis flare. Inflamm Res. 2007;56(7):304-10. doi: 10.1007/s00011- 007-6147-x.
- Muñoz-Garcia J, Cochonneau D, Télétchéa S, Moranton E, Lanoe D, Brion R, et al. The twin cytokines interleukin-34 and CSF-1: masterful conductors of macrophage homeostasis. Theranostics. 2021;11(4):1568-93. doi: 10.7150/thno.50683.
- Guilliams M, Thierry GR, Bonnardel J, Bajenoff M. Establishment and maintenance of the macrophage niche. Immunity. 2020;52(3):434-51. doi: 10.1016/j. immuni.2020.02.015.
- Ushach I, Zlotnik A. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colonystimulating factor (M-CSF) on cells of the myeloid lineage. J Leukoc Biol. 2016;100(3):481-9. doi: 10.1189/jlb.3RU0316- 144R.
- Freuchet A, Salama A, Remy S, Guillonneau C, Anegon I. IL-34 and CSF-1, deciphering similarities and differences at steady state and in diseases. J Leukoc Biol. 2021;110(4):771- 96. doi: 10.1002/jlb.3ru1120-773r.
- Ju S, Zhang D, Wang Y, Ni H, Kong X, Zhong R. Correlation of the expression levels of BLyS and its receptors mRNA in patients with systemic lupus erythematosus. Clin Biochem. 2006;39(12):1131-7. doi: 10.1016/j. clinbiochem.2006.09.010.
- Iwata Y, Boström EA, Menke J, Rabacal WA, Morel L, Wada T, et al. Aberrant macrophages mediate defective kidney repair that triggers nephritis in lupus-susceptible mice. J Immunol. 2012;188(9):4568-80. doi: 10.4049/jimmunol.1102154.
- Bloom RD, Florquin S, Singer GG, Brennan DC, Kelley VR. Colony stimulating factor-1 in the induction of lupus nephritis. Kidney Int. 1993;43(5):1000-9. doi: 10.1038/ki.1993.141.
- Mirfeizi Z, Mahmoudi M, Naghibi M, Hatef M, Sharifipour F, Jokar M, et al. Urine monocyte chemoattractant protein- 1(UMCP-1) as a biomarker of renal involvement in systemic lupus erythematosus. Iran J Basic Med Sci. 2012;15(6):1191-5.