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Urinary soluble CD163 is a good biomarker for renal disease activity in lupus nephritis

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Abstract

Objectives

Activated macrophages expressing CD163 (M2) are the most abundant macrophage subtype in renal biopsies from lupus nephritis (LN) patients. We studied the role of proteolytically cleaved soluble CD163 (sCD163) as a biomarker of LN disease activity.

Methods

SLE patients were classified as active LN (AN), inactive disease (ID), and active non-renal disease (ANR). Urine and plasma samples were collected at baseline from all patients and at 3 monthly follow-up from AN patients. sCD163 was measured by ELISA. Urine values were normalized to urinary creatinine excretion and expressed as pg/mg. Urine samples from 25 healthy controls (HC) and 20 rheumatoid arthritis patients served as disease controls (DC).

Results

Among the 122 patients studied (114 females, 57 AN, 42 ID, 23 ANR), baseline median urinary sCD163 in the AN group (114.01 pg/mg) was significantly higher (p < 0.001) as compared with ID (10.34 pg/mg), ANR (3.82 pg/mg), HC (0 pg/mg), and DC (7.56 pg/mg) groups and showed modest correlation with renal SLEDAI (r = 0.47; p < 0.001). Urinary sCD163 performed the best on receiver operating characteristics (ROC) analysis (AUC = 0.76) at baseline to differentiate between AN and ANR as compared with plasma sCD163, anti-ds DNA antibodies, and C3 and C4.

In follow-up study, urinary sCD163 decreased significantly (p < 0.001) in AN patients at 3 (22.07 pg/mg), 6 (12.7 pg/mg), 9 (11.09 pg/mg), and 12 months (7.2 pg/mg). In 4 patients who had either relapse or developed CKD, urinary sCD163 levels correlated with the changing disease activity.

Conclusions

Urinary sCD163 is a good biomarker of LN disease activity.

Key Points

• Urinary sCD163 levels are raised in patients with active lupus nephritis and correlate with renal SLEDAI.

• Urinary sCD163 levels fall after treatment and may be helpful in monitoring response to therapy in lupus nephritis.

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References

  1. Misra R, Gupta R (2009) Biomarkers in lupus nephritis. Int J Rheum Dis 18:219–232

    Article  Google Scholar 

  2. Kopetschke K, Klocke J, Grießbach AS et al (2015) The cellular signature of urinary immune cells in lupus nephritis: new insights into potential biomarkers. Arthritis Res Ther 17:94

    Article  Google Scholar 

  3. Olmes G, Büttner-Herold M, Ferrazzi F, Distel L, Amann K, Daniel C (2016) CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis. Arthritis Res Ther 18:–90

  4. Bhattacharya S, Aggarwal A (2019) M2 macrophages and their role in rheumatic diseases. Rheumatol Int 39:769–780

    Article  CAS  Google Scholar 

  5. Kishimoto D, Kirino Y, Tamura M et al (2018) Dysregulated heme oxygenase-1low M2-like macrophages augment lupus nephritis via Bach1 induced by type I interferons. Arthritis Res Ther 20:64

    Article  Google Scholar 

  6. O’Reilly VP, Wong L, Kennedy C et al (2016) Urinary soluble CD163 in active renal vasculitis. J Am Soc Nephrol 27:2906–2916

    Article  Google Scholar 

  7. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725

    Article  CAS  Google Scholar 

  8. Gladman DD, Ibañez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291

    PubMed  Google Scholar 

  9. Hahn BH, McMahon MA, Wilkinson A et al (2012) American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 64:797–808

    Article  Google Scholar 

  10. The American College of Rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials. Renal Disease Subcommittee of the American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria. (2006) Arthritis Rheum 54:421–32

  11. Ma C, Xia Y, Yang Q, Zhao Y (2019) The contribution of macrophages to systemic lupus erythematosus. Clin Immunol 207:1–9

    Article  CAS  Google Scholar 

  12. Nakayama W, Jinnin M, Makino K et al (2012) CD163 expression is increased in the involved skin and sera of patients with systemic lupus erythematosus. Eur J Dermatol 22:512–517

    Article  CAS  Google Scholar 

  13. Nishino A, Katsumata Y, Kawasumi H, Hirahara S, Kawaguchi Y, Yamanaka H (2019) Usefulness of soluble CD163 as a biomarker for macrophage activation syndrome associated with systemic lupus erythematosus. Lupus 986–994

  14. Zizzo G, Guerrieri J, Dittman LM, Merrill JT, Cohen PL (2013) Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity. Arthritis Res Ther 15(6):R212

    Article  Google Scholar 

  15. Zhu H, Sun X, Zhu L, Hu F, Shi L, Li Z, Su Y (2014) The expression and clinical significance of different forms of Mer receptor tyrosine kinase in systemic lupus erythematosus. J Immunol Res 2014:431896

    Article  Google Scholar 

  16. Li J, Liu CH, Xu DL, Gao B (2015) Significance of CD163-positive macrophages in proliferative glomerulonephritis. Am J Med Sci 350:387–392

    Article  Google Scholar 

  17. Endo N, Tsuboi N, Furuhashi K, Shi Y, du Q, Abe T, Hori M, Imaizumi T, Kim H, Katsuno T, Ozaki T, Kosugi T, Matsuo S, Maruyama S (2016) Urinary soluble CD163 level reflects glomerular inflammation in human lupus nephritis. Nephrol Dial Transplant 31:2023–2033

    Article  CAS  Google Scholar 

  18. Gupta R, Yadav A, Aggarwal A (2016) Longitudinal assessment of monocyte chemoattractant protein-1 in lupus nephritis as a biomarker of disease activity. Clin Rheumatol 35(11):2707–2714

    Article  Google Scholar 

  19. Dekkema GJ, Abdulahad WH, Bijma T, Moran SM, Ryan L, Little MA, Stegeman CA, Heeringa P, Sanders JSF (2019) Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort study. Nephrol Dial Transplant 34:234–242

    Article  CAS  Google Scholar 

  20. Gupta R, Yadav A, Misra R, Aggarwal A (2015) Urinary sCD25 as a biomarker of lupus nephritis disease activity. Lupus 24:273–279

    Article  CAS  Google Scholar 

  21. Phatak S, Chaurasia S, Mishra SK, Gupta R, Agrawal V, Aggarwal A, Misra R (2017) Urinary B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL): potential biomarkers of active lupus nephritis. Clin Exp Immunol 187:376–382

    Article  CAS  Google Scholar 

  22. Moran SM, Monach PA, Zgaga L et al (2020) Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrol Dial Transplant 35(2):283–291

    CAS  PubMed  Google Scholar 

  23. Lu J, Cao Q, Zheng D, Sun Y, Wang C, Yu X, Wang Y, Lee VWS, Zheng G, Tan TK, Wang X, Alexander SI, Harris DCH, Wang Y (2013) Discrete functions of M2a and M2c macrophage subsets determine their relative efficacy in treating chronic kidney disease. Kidney Int 84:745–755

    Article  CAS  Google Scholar 

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Funding

This project was partially supported by the Dept. of Biotechnology, Government of India research grant (BT/PR15397/MED/30/604/2011) to AA and partially by the India Rheumatology Association (IRA) research grant to RG.

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Author notes

  1. Ranjan Gupta

    Present address: Department of Rheumatology, All India Institute of Medical Sciences, New Delhi, India

Authors and Affiliations

  1. Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India

    Ranjan Gupta, Akhilesh Yadav & Amita Aggarwal

Authors
  1. Ranjan Gupta
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  2. Akhilesh Yadav
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  3. Amita Aggarwal
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Corresponding author

Correspondence to Amita Aggarwal.

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The institutional ethics committee approved the study and informed consent was taken from all the enrolled patients and control subjects.

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Gupta, R., Yadav, A. & Aggarwal, A. Urinary soluble CD163 is a good biomarker for renal disease activity in lupus nephritis. Clin Rheumatol 40, 941–948 (2021). https://doi.org/10.1007/s10067-020-05343-6

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  • DOI: https://doi.org/10.1007/s10067-020-05343-6

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