CD163 and CD206 expression define distinct macrophage subsets involved in active ANCA-associated glomerulonephritis

Joop P Aendekerk; William F Jiemy; Elisabeth Raveling-Eelsing; Nele Bijnens; Myrurgia A Abdul-Hamid; Inge M Strating; Gerjan J Dekkema; Jan-Stephan F Sanders; Coen A Stegeman; Jan G M C Damoiseaux; Mark A Little; Peter Heeringa; Pieter van Paassen

doi:10.1016/j.jaut.2022.102914

CD163 and CD206 expression define distinct macrophage subsets involved in active ANCA-associated glomerulonephritis

Joop P Aendekerk, William F Jiemy, Elisabeth Raveling-Eelsing, Nele Bijnens, Myrurgia A Abdul-Hamid, Inge M Strating, Gerjan J Dekkema, Jan-Stephan F Sanders, Coen A Stegeman, Jan G M C Damoiseaux, Mark A Little, Peter Heeringa, Pieter van Paassen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

INTRODUCTION: Macrophages are key players in the immunopathology of anti-neutrophil cytoplasmic antibody (ANCA) mediated-vasculitis (AAV) with glomerulonephritis (ANCA GN). Different macrophage phenotypes are expected to play distinct roles in ANCA GN. Macrophages expressing CD163 and CD206 are found in lesions associated with ANCA GN. Hence, we aimed to investigate the clinicopathological significance of CD206 and CD163 in ANCA GN in a multicenter retrospective cohort study.

MATERIAL AND METHODS: Patients with ANCA-associated vasculitis, with clinical data, serum and urine samples were included from three cohorts. Serum soluble CD206 (ssCD206) and urinary soluble CD163 (usCD163) levels were measured. Human kidney tissue samples (n = 53) were stained for CD206 and CD163 using immunohistochemistry and immunofluorescence, and findings were correlated with clinical and pathological data.

RESULTS: In total, 210 patients were included (i.e., ANCA GN, n = 134; AAV without GN, n = 24; AAV in remission n = 52). Increased levels of both ssCD206 and usCD163 were seen in ANCA GN. High levels of ssCD206 declined after reaching remission, however, ssCD206 did not improve the accuracy of usCD163 to detect ANCA GN. Soluble markers correlated with histopathological findings. CD163+CD206- macrophages were found in the glomerulus and may play pivotal roles in glomerulonephritis, whereas CD206+CD163- and CD206+CD163+ macrophages were located tubulointerstitially and likely play a more prominent role in ANCA-associated tubulointerstitial inflammation. In ANCA GN patients increasing levels of ssCD206 increased the risk for end-stage renal disease and mortality.

CONCLUSIONS: Our results confirm and extend the notion that CD206+ and CD163+ macrophages are prominent components of the cellular infiltrate in ANCA GN. We found distinct macrophage phenotypes that may play distinct roles in the immunopathology of ANCA GN and elaborate on a potential mechanism underlying the findings of this study. usCD163 remains an excellent marker to detect active ANCA GN, whereas ssCD206 seems a more prominent marker for risk prediction.

Original language	English
Article number	102914
Number of pages	11
Journal	Journal of Autoimmunity
Volume	133
Early online date	29 Sept 2022
DOIs	https://doi.org/10.1016/j.jaut.2022.102914
Publication status	Published - Dec 2022

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Aendekerk, J. P., Jiemy, W. F., Raveling-Eelsing, E., Bijnens, N., Abdul-Hamid, M. A., Strating, I. M., Dekkema, G. J., Sanders, J.-S. F., Stegeman, C. A., Damoiseaux, J. G. M. C., Little, M. A., Heeringa, P., & van Paassen, P. (2022). CD163 and CD206 expression define distinct macrophage subsets involved in active ANCA-associated glomerulonephritis. Journal of Autoimmunity, 133, Article 102914. https://doi.org/10.1016/j.jaut.2022.102914

@article{700277a8f37347eda61cefbdedcddba5,

title = "CD163 and CD206 expression define distinct macrophage subsets involved in active ANCA-associated glomerulonephritis",

abstract = "INTRODUCTION: Macrophages are key players in the immunopathology of anti-neutrophil cytoplasmic antibody (ANCA) mediated-vasculitis (AAV) with glomerulonephritis (ANCA GN). Different macrophage phenotypes are expected to play distinct roles in ANCA GN. Macrophages expressing CD163 and CD206 are found in lesions associated with ANCA GN. Hence, we aimed to investigate the clinicopathological significance of CD206 and CD163 in ANCA GN in a multicenter retrospective cohort study.MATERIAL AND METHODS: Patients with ANCA-associated vasculitis, with clinical data, serum and urine samples were included from three cohorts. Serum soluble CD206 (ssCD206) and urinary soluble CD163 (usCD163) levels were measured. Human kidney tissue samples (n = 53) were stained for CD206 and CD163 using immunohistochemistry and immunofluorescence, and findings were correlated with clinical and pathological data.RESULTS: In total, 210 patients were included (i.e., ANCA GN, n = 134; AAV without GN, n = 24; AAV in remission n = 52). Increased levels of both ssCD206 and usCD163 were seen in ANCA GN. High levels of ssCD206 declined after reaching remission, however, ssCD206 did not improve the accuracy of usCD163 to detect ANCA GN. Soluble markers correlated with histopathological findings. CD163+CD206- macrophages were found in the glomerulus and may play pivotal roles in glomerulonephritis, whereas CD206+CD163- and CD206+CD163+ macrophages were located tubulointerstitially and likely play a more prominent role in ANCA-associated tubulointerstitial inflammation. In ANCA GN patients increasing levels of ssCD206 increased the risk for end-stage renal disease and mortality.CONCLUSIONS: Our results confirm and extend the notion that CD206+ and CD163+ macrophages are prominent components of the cellular infiltrate in ANCA GN. We found distinct macrophage phenotypes that may play distinct roles in the immunopathology of ANCA GN and elaborate on a potential mechanism underlying the findings of this study. usCD163 remains an excellent marker to detect active ANCA GN, whereas ssCD206 seems a more prominent marker for risk prediction.",

author = "Aendekerk, {Joop P} and Jiemy, {William F} and Elisabeth Raveling-Eelsing and Nele Bijnens and Abdul-Hamid, {Myrurgia A} and Strating, {Inge M} and Dekkema, {Gerjan J} and Sanders, {Jan-Stephan F} and Stegeman, {Coen A} and Damoiseaux, {Jan G M C} and Little, {Mark A} and Peter Heeringa and {van Paassen}, Pieter",

year = "2022",

month = dec,

doi = "10.1016/j.jaut.2022.102914",

language = "English",

volume = "133",

journal = "Journal of Autoimmunity",

issn = "0896-8411",

publisher = "Elsevier Science",

}

Aendekerk, JP, Jiemy, WF, Raveling-Eelsing, E, Bijnens, N, Abdul-Hamid, MA, Strating, IM, Dekkema, GJ, Sanders, J-SF, Stegeman, CA, Damoiseaux, JGMC, Little, MA, Heeringa, P & van Paassen, P 2022, 'CD163 and CD206 expression define distinct macrophage subsets involved in active ANCA-associated glomerulonephritis', Journal of Autoimmunity, vol. 133, 102914. https://doi.org/10.1016/j.jaut.2022.102914

TY - JOUR

T1 - CD163 and CD206 expression define distinct macrophage subsets involved in active ANCA-associated glomerulonephritis

AU - Aendekerk, Joop P

AU - Jiemy, William F

AU - Raveling-Eelsing, Elisabeth

AU - Bijnens, Nele

AU - Abdul-Hamid, Myrurgia A

AU - Strating, Inge M

AU - Dekkema, Gerjan J

AU - Sanders, Jan-Stephan F

AU - Stegeman, Coen A

AU - Damoiseaux, Jan G M C

AU - Little, Mark A

AU - Heeringa, Peter

AU - van Paassen, Pieter

PY - 2022/12

Y1 - 2022/12

N2 - INTRODUCTION: Macrophages are key players in the immunopathology of anti-neutrophil cytoplasmic antibody (ANCA) mediated-vasculitis (AAV) with glomerulonephritis (ANCA GN). Different macrophage phenotypes are expected to play distinct roles in ANCA GN. Macrophages expressing CD163 and CD206 are found in lesions associated with ANCA GN. Hence, we aimed to investigate the clinicopathological significance of CD206 and CD163 in ANCA GN in a multicenter retrospective cohort study.MATERIAL AND METHODS: Patients with ANCA-associated vasculitis, with clinical data, serum and urine samples were included from three cohorts. Serum soluble CD206 (ssCD206) and urinary soluble CD163 (usCD163) levels were measured. Human kidney tissue samples (n = 53) were stained for CD206 and CD163 using immunohistochemistry and immunofluorescence, and findings were correlated with clinical and pathological data.RESULTS: In total, 210 patients were included (i.e., ANCA GN, n = 134; AAV without GN, n = 24; AAV in remission n = 52). Increased levels of both ssCD206 and usCD163 were seen in ANCA GN. High levels of ssCD206 declined after reaching remission, however, ssCD206 did not improve the accuracy of usCD163 to detect ANCA GN. Soluble markers correlated with histopathological findings. CD163+CD206- macrophages were found in the glomerulus and may play pivotal roles in glomerulonephritis, whereas CD206+CD163- and CD206+CD163+ macrophages were located tubulointerstitially and likely play a more prominent role in ANCA-associated tubulointerstitial inflammation. In ANCA GN patients increasing levels of ssCD206 increased the risk for end-stage renal disease and mortality.CONCLUSIONS: Our results confirm and extend the notion that CD206+ and CD163+ macrophages are prominent components of the cellular infiltrate in ANCA GN. We found distinct macrophage phenotypes that may play distinct roles in the immunopathology of ANCA GN and elaborate on a potential mechanism underlying the findings of this study. usCD163 remains an excellent marker to detect active ANCA GN, whereas ssCD206 seems a more prominent marker for risk prediction.

AB - INTRODUCTION: Macrophages are key players in the immunopathology of anti-neutrophil cytoplasmic antibody (ANCA) mediated-vasculitis (AAV) with glomerulonephritis (ANCA GN). Different macrophage phenotypes are expected to play distinct roles in ANCA GN. Macrophages expressing CD163 and CD206 are found in lesions associated with ANCA GN. Hence, we aimed to investigate the clinicopathological significance of CD206 and CD163 in ANCA GN in a multicenter retrospective cohort study.MATERIAL AND METHODS: Patients with ANCA-associated vasculitis, with clinical data, serum and urine samples were included from three cohorts. Serum soluble CD206 (ssCD206) and urinary soluble CD163 (usCD163) levels were measured. Human kidney tissue samples (n = 53) were stained for CD206 and CD163 using immunohistochemistry and immunofluorescence, and findings were correlated with clinical and pathological data.RESULTS: In total, 210 patients were included (i.e., ANCA GN, n = 134; AAV without GN, n = 24; AAV in remission n = 52). Increased levels of both ssCD206 and usCD163 were seen in ANCA GN. High levels of ssCD206 declined after reaching remission, however, ssCD206 did not improve the accuracy of usCD163 to detect ANCA GN. Soluble markers correlated with histopathological findings. CD163+CD206- macrophages were found in the glomerulus and may play pivotal roles in glomerulonephritis, whereas CD206+CD163- and CD206+CD163+ macrophages were located tubulointerstitially and likely play a more prominent role in ANCA-associated tubulointerstitial inflammation. In ANCA GN patients increasing levels of ssCD206 increased the risk for end-stage renal disease and mortality.CONCLUSIONS: Our results confirm and extend the notion that CD206+ and CD163+ macrophages are prominent components of the cellular infiltrate in ANCA GN. We found distinct macrophage phenotypes that may play distinct roles in the immunopathology of ANCA GN and elaborate on a potential mechanism underlying the findings of this study. usCD163 remains an excellent marker to detect active ANCA GN, whereas ssCD206 seems a more prominent marker for risk prediction.

U2 - 10.1016/j.jaut.2022.102914

DO - 10.1016/j.jaut.2022.102914

M3 - Article

C2 - 36183584

SN - 0896-8411

VL - 133

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

M1 - 102914

ER -