CD163 M2c-like macrophages predominate in renal biopsies from patients with lupus nephritisReportar como inadecuado

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Arthritis Research and Therapy

, 18:90

First Online: 18 April 2016Received: 10 August 2015Accepted: 05 April 2016


BackgroundThe 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.

MethodUsing 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.

ResultsThe 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.

ConclusionM2-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.

KeywordsLupus nephritis Macrophages T-reg-cells Macrophage subtypes AbbreviationsBSAbovine serum albumin

CCR2chemokine receptor type 2

ERKextracellular signal related

FFPEformalin-fixed paraffin-embedded

FoxP3forkhead-box-protein P3

GFRglomerular filtration rate

GSIglomerulosclerosis score

IFinterstitial fibrosis

IFTAInternational Fibrosis and Tubular Atrophy


INF-ɣinterferon gamma

iNOSinducible nitric oxide synthase

ISN-RPSInternational Society of Nephrology-Renal Pathology Society

LNlupus nephritis


SLEsystemic lupus erythematosus

TAtubular atrophy

TNF-αtumor necrosis factor alpha

Tregregulatory T cells

TSItubular injury score

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Autor: Gregor Olmes - Maike Büttner-Herold - Fulvia Ferrazzi - Luitpold Distel - Kerstin Amann - Christoph Daniel


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