Exploring Frequencies of Circulating Specific Th17 Cells against Myeloperoxidase and Proteinase 3 in ANCA Associated Vasculitis

• Published in: International journal of molecular sciences 2019-11, Vol.20 (23), p.5820
• Main Authors: Martinez Valenzuela, Laura, Draibe, Juliana, Quero, Maria, Fulladosa, Xavier, Cruzado, Josep Maria, Bestard, Oriol, Torras, Juan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - blood; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - diagnosis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - immunology; Antigens; Antineutrophil cytoplasmic antibodies; Biomarkers - blood; C-reactive protein; Cell number; Creatinine; Cytoplasm; Depletion; Disease; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunospot Assay - methods; Female; Helper cells; Humans; Interleukin 17; Leukocytes (mononuclear); Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Male; Middle Aged; Myeloblastin - immunology; Neutrophils; Patients; Peripheral blood mononuclear cells; Peroxidase; Peroxidase - immunology; Proteinase; Proteinase 3; Remission; Serologic Tests - methods; Th17 Cells - immunology; Urine; Vasculitis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20235820

Background: The role of the T helper 17 (Th17) cell subset in anti-neutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV) is controversial. We hypothesized that a specific Th17 response to myeloperoxidase (MPO) or proteinase 3 (PR3) is detectable in AAV patients and is different among the disease phases. We analyzed 43 AAV patients with renal involvement (21 acute and 22 remission patients), and 12 healthy controls. Peripheral blood mononuclear cells (PBMCs) were cultured with PR3/MPO over 48 h. Thereafter, frequencies of MPO/PR3-specific Th17 cells were assessed using an enzyme-linked immunosorbent spot (ELISpot) assay. Supernatant IL-17 concentration was quantified using ELISA. Finally, specific Th17 response after depletion of T regulatory lymphocytes (T-regs) in some remission patients was compared to the non T-reg-depleted response. Specific Th17 cell number was higher in acute patients compared to remission ( = 0.004). Specific Th17 cell number performed well in the disease activity detection (ROC curve area under the curve (AUC) = 0.87; = 0.0001) with an optimal cut-off of 6 spots/million. Patients above this cut-off showed higher serum creatinine ( = 0.004), C-reactive protein (CRP) ( = 0.001) and ANCA titer ( = 0.032). Supernatant IL-17 concentration was higher in acute patients compared to remission ( = 0.035) and did not normalize to healthy control levels ( = 0.01). A specific Th17 cell response is present in AAV patients. This response is more pronounced in the acute phase, but persists in remission.