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CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis.

Olmes G, Büttner-Herold M, Ferrazzi F, Distel L, Amann K, Daniel C - Arthritis Res. Ther. (2016)

Bottom Line: In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role.Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054, Erlangen, Germany.

ABSTRACT

Background: The role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters.

Method: Using immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II-V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test.

Results: The mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role. Cluster analysis using macrophage subtype numbers in different renal compartments revealed three main clusters showing cluster 1 dominated by class V. Clusters 2 and 3 were dominated by lupus class IV indicating that this class can be further differentiated by its macrophage population. The number of tubulointerstitial FoxP3+ cells correlated with all investigated macrophage subtypes showing the strongest association to numbers of M2a-like macrophages. Kidney function, as assessed by serum creatinine and serum urea, correlated positively with the number of total CD68+, M2a-like and M2c-like macrophages in the tubulointerstitium. In addition, total CD68+ and M2c-like macrophage numbers highly correlated with Austin activity score. Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.

Conclusion: M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

No MeSH data available.


Related in: MedlinePlus

Clustering of patients with lupus nephritis using frequencies of different macrophage subsets. Patients with diagnosed lupus nephritis were clustered on the basis of the profiles of macrophage subsets in different renal compartments. International Society of Nephrology/Renal Pathology Society (ISN/RPS) systemic lupus erythematosus (SLE) classes of biopsies in each cluster are indicated using a color code (pale green class II, light green class III, olive green class IV, viridian class V). The frequencies of SLE ISN/RPS classes in the clusters are shown as the number of cases within the cluster per total number of patients allocated to this class in this study. iNOS inducible nitric oxide synthesase
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Fig4: Clustering of patients with lupus nephritis using frequencies of different macrophage subsets. Patients with diagnosed lupus nephritis were clustered on the basis of the profiles of macrophage subsets in different renal compartments. International Society of Nephrology/Renal Pathology Society (ISN/RPS) systemic lupus erythematosus (SLE) classes of biopsies in each cluster are indicated using a color code (pale green class II, light green class III, olive green class IV, viridian class V). The frequencies of SLE ISN/RPS classes in the clusters are shown as the number of cases within the cluster per total number of patients allocated to this class in this study. iNOS inducible nitric oxide synthesase

Mentions: Next we asked if the information on macrophage subtypes and its frequencies in different renal compartments could be used to confirm the classical histomorphological classification or is useful for the description of a new classification. To this aim patients were clustered on the basis of the macrophage subpopulation profiles (Fig. 4). In the heatmap in the figure each row corresponds to a patient, while the columns represent the abundance of different macrophage subtypes in the renal compartments (glomeruli, tubulointerstitium, and medulla), visualized by a color code ranging from blue (low) to red (high). Interestingly, three major groups with different macrophage subpopulation profiles were identified by cluster analysis. Each cluster included patients who could be allocated to more than one ISN/RPS class. However, two clusters (cluster 1 + 2) partially reflected the classical histomorphological classification. Cluster 1 contains more than 50 % of patient biopsies allocated to classes II and V. This cluster is characterized by low macrophage infiltration in all renal compartments. Cluster 2 is dominated by patients of lupus ISN/RPS class IV. It contains nearly 30 % of all ISN/RPS class IV patients and also some patients of ISN/RPS class II and III. This cluster is characterized by high infiltration of M2a and M2c-like macrophages in all renal compartments. In cluster 3 most biopsies are from patients with lupus nephritis class IV (n = 8), but the frequency was comparable to classes II and V, when calculated as the percentage of the respective ISN/RPS class cases included in this study. This cluster represents patients with more M1-like macrophages in the glomeruli, tubuli, and medulla compared to clusters 1 and 2 (Fig. 4).Fig. 4


CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis.

Olmes G, Büttner-Herold M, Ferrazzi F, Distel L, Amann K, Daniel C - Arthritis Res. Ther. (2016)

Clustering of patients with lupus nephritis using frequencies of different macrophage subsets. Patients with diagnosed lupus nephritis were clustered on the basis of the profiles of macrophage subsets in different renal compartments. International Society of Nephrology/Renal Pathology Society (ISN/RPS) systemic lupus erythematosus (SLE) classes of biopsies in each cluster are indicated using a color code (pale green class II, light green class III, olive green class IV, viridian class V). The frequencies of SLE ISN/RPS classes in the clusters are shown as the number of cases within the cluster per total number of patients allocated to this class in this study. iNOS inducible nitric oxide synthesase
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835936&req=5

Fig4: Clustering of patients with lupus nephritis using frequencies of different macrophage subsets. Patients with diagnosed lupus nephritis were clustered on the basis of the profiles of macrophage subsets in different renal compartments. International Society of Nephrology/Renal Pathology Society (ISN/RPS) systemic lupus erythematosus (SLE) classes of biopsies in each cluster are indicated using a color code (pale green class II, light green class III, olive green class IV, viridian class V). The frequencies of SLE ISN/RPS classes in the clusters are shown as the number of cases within the cluster per total number of patients allocated to this class in this study. iNOS inducible nitric oxide synthesase
Mentions: Next we asked if the information on macrophage subtypes and its frequencies in different renal compartments could be used to confirm the classical histomorphological classification or is useful for the description of a new classification. To this aim patients were clustered on the basis of the macrophage subpopulation profiles (Fig. 4). In the heatmap in the figure each row corresponds to a patient, while the columns represent the abundance of different macrophage subtypes in the renal compartments (glomeruli, tubulointerstitium, and medulla), visualized by a color code ranging from blue (low) to red (high). Interestingly, three major groups with different macrophage subpopulation profiles were identified by cluster analysis. Each cluster included patients who could be allocated to more than one ISN/RPS class. However, two clusters (cluster 1 + 2) partially reflected the classical histomorphological classification. Cluster 1 contains more than 50 % of patient biopsies allocated to classes II and V. This cluster is characterized by low macrophage infiltration in all renal compartments. Cluster 2 is dominated by patients of lupus ISN/RPS class IV. It contains nearly 30 % of all ISN/RPS class IV patients and also some patients of ISN/RPS class II and III. This cluster is characterized by high infiltration of M2a and M2c-like macrophages in all renal compartments. In cluster 3 most biopsies are from patients with lupus nephritis class IV (n = 8), but the frequency was comparable to classes II and V, when calculated as the percentage of the respective ISN/RPS class cases included in this study. This cluster represents patients with more M1-like macrophages in the glomeruli, tubuli, and medulla compared to clusters 1 and 2 (Fig. 4).Fig. 4

Bottom Line: In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role.Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054, Erlangen, Germany.

ABSTRACT

Background: The role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters.

Method: Using immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II-V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test.

Results: The mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role. Cluster analysis using macrophage subtype numbers in different renal compartments revealed three main clusters showing cluster 1 dominated by class V. Clusters 2 and 3 were dominated by lupus class IV indicating that this class can be further differentiated by its macrophage population. The number of tubulointerstitial FoxP3+ cells correlated with all investigated macrophage subtypes showing the strongest association to numbers of M2a-like macrophages. Kidney function, as assessed by serum creatinine and serum urea, correlated positively with the number of total CD68+, M2a-like and M2c-like macrophages in the tubulointerstitium. In addition, total CD68+ and M2c-like macrophage numbers highly correlated with Austin activity score. Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.

Conclusion: M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

No MeSH data available.


Related in: MedlinePlus