Article Text

THU0498 Increase of CXCR3-CCR4+CCR6+CCR10- Memory T Helper Cells (TH17-LIKE) in Patients with Granulomatosis and Polyangiitis (GPA)
  1. B. Jakiela,
  2. K. Wawrzycka,
  3. W. Szczeklik,
  4. M. Hubalewska-Mazgaj,
  5. M. Surmiak,
  6. M. Sanak,
  7. J. Musial
  1. Dpt of Medicine, Jagiellonian University Medical College, Krakow, Poland


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

DOI 10.1136/annrheumdis-2014-eular.3614

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.