M1 and M2 Macrophage Polarization Correlates with Activity and Chronicity Indices in Lupus Nephritis

<b><b>Background:</b></b> Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterized by inflammation and immune dysregulation in the kidneys. The role of macrophage polarization in LN progression remains underexplored. <b>Objecti...

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Main Authors: Chutima Chavanisakun, Rassamon Keawvichit, Nontawat Benjakul
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Language:English
Published: MDPI AG 2025-01-01
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Online Access:https://www.mdpi.com/2075-1729/15/1/55
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author Chutima Chavanisakun
Rassamon Keawvichit
Nontawat Benjakul
author_facet Chutima Chavanisakun
Rassamon Keawvichit
Nontawat Benjakul
author_sort Chutima Chavanisakun
collection DOAJ
description <b><b>Background:</b></b> Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterized by inflammation and immune dysregulation in the kidneys. The role of macrophage polarization in LN progression remains underexplored. <b>Objective:</b> This study examined the association between tubulointerstitial M1/M2 macrophage subpopulations and LN indices of activity and chronicity. <b>Materials and Methods:</b> We retrospectively reviewed 160 renal biopsy specimens in patients with LN (ISN/RPS classes II–V) from the database of the Department of Anatomical Pathology, the Faculty of Medicine Vajira Hospital, Navamindradhiraj University (2012–2021). Additional immunohistochemical analysis included CD68, iNOS, CD206, CD163, and evaluation of infiltration with M1 (iNOS+), M2a (CD206+), and M2c macrophages (CD163+). Moreover, clinical information at the time of the renal biopsy, including age, sex, and laboratory findings, was obtained from the electronic medical records. The data were correlated with the macrophage infiltration using the Spearman test. <b>Results:</b> Lupus nephritis biopsies with ISN/RPS class II–V were included (class II: 3 cases (2%), III: 30 cases (19%), III + V: 16 cases (10%), IV: 73 cases (46%), IV + V: 18 cases (11%), and V: 20 cases (12%)). In addition, the mean age of SLE patients at the time of biopsy was 33 years (range: 19–47 years). Most patients were females (n = 141; 88%). The population of CD68+ macrophages was related to serum creatinine (<i>p</i> < 0.001; rs = 0.34). We detected predominantly M2 macrophages across all LN classes, but M1 macrophages demonstrated significant correlations with the activity index (<i>p</i> < 0.001; rs = 0.43). Conversely, M2a and M2c subpopulations were strongly associated with the chronicity index (M2a: <i>p</i> < 0.001, rs = 0.48; M2c: <i>p</i> = 0.024, rs = 0.18). Total macrophages correlated with both indices (activity: <i>p</i> < 0.001, rs = 0.44; chronicity: <i>p</i> < 0.001, rs = 0.42). <b>Conclusions:</b> In lupus nephritis, the predominant population of macrophages is M2. Correlations were noted between the subpopulations of M1 and M2c macrophages and the activity and chronicity indices, respectively. In addition, macrophage populations correlated with disease progression, but the significance of this association in disease progression remains uncertain.
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spelling doaj-art-1577d6758b8b4c37b719f577e945cf382025-01-24T13:38:36ZengMDPI AGLife2075-17292025-01-011515510.3390/life15010055M1 and M2 Macrophage Polarization Correlates with Activity and Chronicity Indices in Lupus NephritisChutima Chavanisakun0Rassamon Keawvichit1Nontawat Benjakul2Department of Anatomical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, 681 Samsen Road, Dusit, Bangkok 10300, ThailandVajira Pathology-Clinical-Correlation Target Research Interest Group, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, 681 Samsen Road, Dusit, Bangkok 10300, ThailandDepartment of Anatomical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, 681 Samsen Road, Dusit, Bangkok 10300, Thailand<b><b>Background:</b></b> Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterized by inflammation and immune dysregulation in the kidneys. The role of macrophage polarization in LN progression remains underexplored. <b>Objective:</b> This study examined the association between tubulointerstitial M1/M2 macrophage subpopulations and LN indices of activity and chronicity. <b>Materials and Methods:</b> We retrospectively reviewed 160 renal biopsy specimens in patients with LN (ISN/RPS classes II–V) from the database of the Department of Anatomical Pathology, the Faculty of Medicine Vajira Hospital, Navamindradhiraj University (2012–2021). Additional immunohistochemical analysis included CD68, iNOS, CD206, CD163, and evaluation of infiltration with M1 (iNOS+), M2a (CD206+), and M2c macrophages (CD163+). Moreover, clinical information at the time of the renal biopsy, including age, sex, and laboratory findings, was obtained from the electronic medical records. The data were correlated with the macrophage infiltration using the Spearman test. <b>Results:</b> Lupus nephritis biopsies with ISN/RPS class II–V were included (class II: 3 cases (2%), III: 30 cases (19%), III + V: 16 cases (10%), IV: 73 cases (46%), IV + V: 18 cases (11%), and V: 20 cases (12%)). In addition, the mean age of SLE patients at the time of biopsy was 33 years (range: 19–47 years). Most patients were females (n = 141; 88%). The population of CD68+ macrophages was related to serum creatinine (<i>p</i> < 0.001; rs = 0.34). We detected predominantly M2 macrophages across all LN classes, but M1 macrophages demonstrated significant correlations with the activity index (<i>p</i> < 0.001; rs = 0.43). Conversely, M2a and M2c subpopulations were strongly associated with the chronicity index (M2a: <i>p</i> < 0.001, rs = 0.48; M2c: <i>p</i> = 0.024, rs = 0.18). Total macrophages correlated with both indices (activity: <i>p</i> < 0.001, rs = 0.44; chronicity: <i>p</i> < 0.001, rs = 0.42). <b>Conclusions:</b> In lupus nephritis, the predominant population of macrophages is M2. Correlations were noted between the subpopulations of M1 and M2c macrophages and the activity and chronicity indices, respectively. In addition, macrophage populations correlated with disease progression, but the significance of this association in disease progression remains uncertain.https://www.mdpi.com/2075-1729/15/1/55systemic lupus erythematosuslupus nephritismacrophagesmacrophage subtypesrenal pathology
spellingShingle Chutima Chavanisakun
Rassamon Keawvichit
Nontawat Benjakul
M1 and M2 Macrophage Polarization Correlates with Activity and Chronicity Indices in Lupus Nephritis
Life
systemic lupus erythematosus
lupus nephritis
macrophages
macrophage subtypes
renal pathology
title M1 and M2 Macrophage Polarization Correlates with Activity and Chronicity Indices in Lupus Nephritis
title_full M1 and M2 Macrophage Polarization Correlates with Activity and Chronicity Indices in Lupus Nephritis
title_fullStr M1 and M2 Macrophage Polarization Correlates with Activity and Chronicity Indices in Lupus Nephritis
title_full_unstemmed M1 and M2 Macrophage Polarization Correlates with Activity and Chronicity Indices in Lupus Nephritis
title_short M1 and M2 Macrophage Polarization Correlates with Activity and Chronicity Indices in Lupus Nephritis
title_sort m1 and m2 macrophage polarization correlates with activity and chronicity indices in lupus nephritis
topic systemic lupus erythematosus
lupus nephritis
macrophages
macrophage subtypes
renal pathology
url https://www.mdpi.com/2075-1729/15/1/55
work_keys_str_mv AT chutimachavanisakun m1andm2macrophagepolarizationcorrelateswithactivityandchronicityindicesinlupusnephritis
AT rassamonkeawvichit m1andm2macrophagepolarizationcorrelateswithactivityandchronicityindicesinlupusnephritis
AT nontawatbenjakul m1andm2macrophagepolarizationcorrelateswithactivityandchronicityindicesinlupusnephritis