Skewing toward Treg and Th2 responses is a characteristic feature of sustained remission in ANCA-positive granulomatosis with polyangiitis.
The objective of our study was to evaluate the T-helper (Th) and regulatory T (Treg) cell profile in ANCA-positive granulomatosis with polyangiitis (GPA) and its relation to disease activity. In a prospective study, we studied two groups of GPA patients: (i) disease flare (active-GPA, BVAS>6, n = 19), (ii) sustained remission (≥ 1-year prior enrollment, inactive-GPA, BVAS = 0, n = 18). 24 age-sex matched healthy subjects served as controls. Active-GPA patients were followed for 6 months and reevaluated during remission (early remission; n = 13). We analyzed subsets of Th-cells (flow cytometry), production of signature cytokines by in vitro stimulated lymphocytes, and broad spectrum of serum cytokines (Luminex). In all GPA patients we observed expansion of effector Th17 cells, and increased production of IL-17A by in vitro stimulated T cells, as compared to controls. Disease flare was characterized by marked reduction in Treg cells, whereas in sustained remission we showed expansion of both Treg and Th2 subset. Finally, analyzing the cytokine profile, we identified CCL23 and LIGHT, as potential biomarkers of active disease. We conclude that in GPA, expansion of Treg and Th2 lymphocytes in parallel to increased Th17 response is a characteristic feature of sustained remission. In contrast, Treg cells are markedly decreased in disease flare.
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Wojciech
W
Szczeklik
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Bogdan
B
Jakieła
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Katarzyna
K
Wawrzycka-Adamczyk
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Marek
M
Sanak
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Magdalena
M
Hubalewska-Mazgaj
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Agnieszka
A
Padjas
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Marcin
M
Surmiak
Department of Integrated Dentistry, Jagiellonian University Medical College, Krakow, Poland.
Katarzyna
K
Szczeklik
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Jan
J
Sznajd
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Jacek
J
Musiał
D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000378:metabolism
D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; C105504:CCL23 protein, human; D019742:Chemokines, CC; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14
ANCA-associated vasculitis; Disease activity; Granulomatosis with Polyangiitis (GPA); Remission; T-lymphocyte