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CD163+ macrophage infiltration reflects disease activity and early treatment response in lupus nephritis
S.D. Crum1, L. Kwant2, G. Sela3, N. Claessen4, J.J. Roelofs5, O. De Boer6, A.J. Kwakernaak7, L. Vogt8, S. Florquin9, M.W. Tsang-A-Sjoe10, T.J. Van Der Putten11, Y. Vegting12, M. Hilhorst13
- Department of Internal Medicine and Department of Nephrology, Amsterdam University Medical Center, University of Amsterdam; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam; and Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands. s.d.crum@amsterdamumc.nl
- Department of Internal Medicine and Department of Nephrology, Amsterdam University Medical Center, University of Amsterdam; and Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
- Department of Internal Medicine and Department of Nephrology, Amsterdam University Medical Center, University of Amsterdam, The Netherlands.
- Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, The Netherlands.
- Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam; Amsterdam Cardiovascular Sciences, Amsterdam; and Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, The Netherlands.
- Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, The Netherlands.
- Department of Internal Medicine and Department of Nephrology, Amsterdam University Medical Center, University of Amsterdam; Amsterdam Institute for Immunology and Infectious Diseases; and Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
- Department of Internal Medicine and Department of Nephrology, Amsterdam University Medical Center, University of Amsterdam; and Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
- Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, The Netherlands.
- Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam; and Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands.
- Department of Internal Medicine and Department of Nephrology, Amsterdam University Medical Center, University of Amsterdam; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam; and Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
- Department of Internal Medicine and Department of Nephrology, Amsterdam University Medical Center, University of Amsterdam; and Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, The Netherlands.
- Department of Internal Medicine and Department of Nephrology, Amsterdam University Medical Center, University of Amsterdam; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam; and Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
CER19639
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PMID: 43001865 [PubMed]
Received: 29/12/2025
Accepted : 21/05/2026
In Press: 05/11/2026
Abstract
OBJECTIVES:
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus, potentially leading to progressive kidney damage and end-stage kidney disease. Emerging evidence suggests that macrophages play a key role in LN pathogenesis. The aim of this study was to investigate associations between renal macrophage infiltration and clinical, histopathological, and long-term renal outcomes in LN.
METHODS:
This retrospective cohort study included 58 biopsy-proven LN patients (2002–2018), with a mean follow-up of 77 months. Immunohistochemistry for CD68, CD163, CD206, and C5aR1 macrophage markers was performed on baseline kidney biopsies. Correlations with histological features and clinical parameters such as kidney function (eGFR), proteinuria and long-term renal outcomes were analysed using correlation matrices and linear mixed models.
RESULTS:
CD163+ macrophage infiltration in glomerular and tubulointerstitial compartments was significantly associated with clinical and histological activity, including lower baseline eGFR, lower complement levels, more leukocyturia/erythrocyturia and higher activity index scores. Patients with high CD163+ infiltration demonstrated significantly greater improvement of eGFR and proteinuria during the first 6 months of treatment post-diagnosis. Conversely, low CD163+ infiltration was associated with increased likelihood of requiring a repeat biopsy. These associations were not observed when stratifying by LN class. CD68+ macrophages showed a similar trend. CD206+ and C5aR1+ macrophages were not associated with markers of disease activity, although high glomerular C5aR1+ infiltration was linked to repeat biopsy. None of the macrophage markers were associated with long-term outcomes such as renal flares, dialysis, or transplantation.
CONCLUSIONS:
CD163+ macrophage infiltration at baseline is associated with active disease and early treatment response in LN, independent of received treatment. While LN class guides treatment choice, CD163+ macrophage infiltration may offer additional prognostic value regarding early therapeutic response. These findings support further investigation of CD163+ macrophages as a biomarker not only providing prognostic information but also helping guide treatment choices beyond the current LN classification system.
