Background/Purpose:  Macrophages may present two main phenotypes indicated as M1 and M2 under different stimuli. M1- and M2-macrophages have divergent functions that range from enhancement of inflammation for M1- to tissue repair and remodeling for M2-macrophages. The balance between tissue M1- or M2-macrophages is variable in different diseases, depending on the pathophysiological process. Granulamatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis that mainly affects the respiratory tract and kidneys. Necrotizing granulomatous inflammation is the hallmark of airways involvement in GPA. The objective of this study is to evaluate the distribution of M1- and M2-macrophage phenotypes in biopsies from the airways of patients with active GPA and to analyze their associations with T- and B cells in those biopsies as well as with nasal carriage of Staphylococcus aureus, disease parameters and therapy.

Methods:  Thirty-five consecutive patients with GPA and active disease involving the airways who underwent a biopsy from the respiratory tract were included in this cross-sectional study. Immunohistochemistry was performed to assess the distribution of macrophages, T- and B cells using the markers CD68, CD3 and CD20, respectively. CD86 was used as M1 marker and CD163 as M2 marker. All slides were scanned and the expression of all markers was quantified in percentage by the positive pixel count algorithm.

Results are expressed as median percentage and interquartile range or as mean percentage and standard deviation. At the time of the biopsy, GPA patients were assessed for nasal carriage of Staphylococcus aureus and treatment. Results: Percentages of macrophages and T cells were significantly higher than that of B cells in the respiratory tract from GPA patients [8.9% (6.4-17.4) vs. 7.4% (5.2-12.4) vs. 4.3 (2.4-8.4); p < 0.0001]. M2 macrophages were more frequent than M1 macrophages [18.2% (9.2-30.5) vs. 32.4 (21.3-41.9); p = 0.0007]. Percentages of T cells were higher in nose biopsies than in biopsies from other sites [8.3% (6.0-15.1) vs. 5.2 (3.0-6.5); p = 0.021] whereas macrophages were more predominant in biopsy sites other than the nose [20.7% (7.2-29.6) vs. 8.4% (6.3-13.6) p = 0.039]. Carriage of Staphylococcus aureus was associated with higher T cell scores [10.5% (6.6-15.4) vs. 5.9% (4.8-7.4) p = 0.014]. The frequency of macrophages, especially M2 macrophages, was higher in GPA patients treated with immunosuppressive agents [44.4% ± 18.3 vs. 29.8% ± 13.2; p = 0.010), whereas daily prednisolone dose was positively correlated with all macrophage markers as follows: CD68 (rho = 0.858; p = 0.001), CD86 (rho = 0.753; p = 0.012) and CD163 (rho = 0.759; p = 0.011). However, in multivariate analysis no independent associations were found between disease parameters or therapy and macrophages or T cells.

Conclusion:  In GPA patients, M2 is the predominant macrophage phenotype in the respiratory tract. Although some associations were observed between macrophages and T cells with therapy and nasal carriage of Staphylococcus aureus, they were not independent from other factors in multivariate analysis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/m2-macrophage-is-the-predominant-phenotype-in-airways-inflammatory-lesions-in-patients-with-granulomatosis-with-polyangiitis/