Background Granulomatosis and polyangiitis (GPA) is a systemic vasculitis associated with anti-proteinase-3 antibodies and T-cell activation. Recruitment of memory T-cells into inflammatory sites depends on chemokine receptors and their specific patterns shape functional properties (e.g. cytokine production) of T helper-cells.
Methods We analyzed subtypes of peripheral blood CD4+ memory (CD45RA-) T-cells identified by the expression of CCR7, CXCR3, CCR4, CCR6 and CCR10 chemokine receptors (multicolor flow cytometry) in GPA patients (n=20, 3 with active disease) and age matched healthy controls (n=18).
Results GPA patients showed decreased percentage of CD4+ naïve cells (mean 20,8 vs. 44,4% in controls) and increased fraction of CD45RA-CCR7- effector memory cells (33,8 vs. 19,2%). A significant increase in the percentage of CXCR3+, CCR4+ and CCR6+ (but not CCR10+) CD4+ cells was also observed. When analyzing co-expression of chemokine receptors, we were able to identify 16 different subpopulations of CD4+ memory T-cells, with only CCR6+ subtypes elevated in GPA. Of note, in GPA we found significant increase in the frequency of CXCR3+CCR4-CCR6+CCR10- CD4+ cells (Th1Th17-like, 13,6 vs. 9,7% in controls) and CXCR3-CCR4+CCR6+CCR10- CD4+ cells (Th17-like, 11,2 vs. 6,4% in controls). The latter subtype was also significantly elevated in analysis limited to CD45RA- cells. Differences in CCR6+ fraction were most evident in patients with lung involvement and in those treated with low dose GCS (<4 mg/d or steroid-free). However, they were not related to additional immunosuppressive treatment (e.g. AZA or MTX) or disease activity.
Conclusions We show that CD4+ cells in GPA patients are switched towards effector memory phenotype, possibly as a signature of disease-related immune activation. We also found expanded CCR6+CCR10- subsets suggesting the involvement of Th1Th17-like and Th17-like cells in the pathogenesis of the disease.
Disclosure of Interest : None declared
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