Review article: The role of CD4 + T cells in ANCA-associated systemic vasculitis (original) (raw)
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T cells in the pathogenesis of ANCA-associated vasculitis: Current knowledge
Folia biologica
Abbreviations: AAV -ANCA-associated vasculitides, ANCAanti-neutrophil cytoplasmic autoantibodies, DTH -delayed-type hypersensitivity, IFN -interferon, IL -interleukin, MPA -microscopic polyangiitis, MPO -myeloperoxidase, PR3 -proteinase 3, RLV -renal-limited vasculitis, TCR -T-cell receptor, TEM -effector memory T cells, WG -Wegener's granulomatosis.
International Journal of Molecular Sciences, 2019
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. Methods: 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. Results: Specific Th17 cell number was higher in acute patients compared to remission (p = 0.004). Specific Th17 cell number performed well in the disease activity detection (ROC curve area under the curve (AUC) = 0.87; p = 0.0001) with an optimal cutoff of 6 spots/million. Patients above this cutoff showed higher serum creatinine (p = 0.004), C-reactive protein (CRP) (p = 0.001) and ANCA titer (p = 0.032). Supernatant IL-17 concentration was higher in acute patients compared to remission (p = 0.035) and did not normalize to healthy control levels (p = 0.01). Conclusions: A specific Th17 cell response is present in AAV patients. This response is more pronounced in the acute phase, but persists in remission.
Phenotypic Characterization of Circulating CD4+ T Cells in ANCA-Associated Vasculitis
Journal of Immunology Research
T cell-mediated immune responses are thought to play an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody- (ANCA-) associated vasculitides (AAV). CD4+ T cells can be divided into subsets depending on their expression of chemokine receptors. In this study, different CD4+ T cell populations in patients with AAV were analysed and compared to healthy blood donors as well as therapy controls. 18 patients with active AAV, 46 in remission, 21 healthy controls (HBD), and 15 therapy controls (TC) were enrolled. CD4+ T cells were divided into Th1, Th2, and Th17 cells and further subdivided into naïve, central memory, effector memory, and effector cells. Regulatory T cells were also analysed. Concentrations of cytokines and chemokines produced by the respective CD4+ T cell subset in plasma from 33 of the patients were measured by ELISA and compared to HBD. Clinical data were collected on all patients. CCL20 concentrations and percentages of Th17 cells (p=0.019) were el...
CD4-Positive Effector Memory T Cells Participate in Disease Expression in ANCA-Associated Vasculitis
2007
Although the cause of ANCA-associated vasculitis (AAV) remains undetermined, the presence of lymphocytic infiltrates in inflammatory lesions of patients suggests that vascular damage is immune mediated. Studies over the past decade have implicated a role for T-cells in the pathogenesis of AAV as altered T-cell phenotype has been observed in this disorder. The distribution of T-cell subpopulations has been analyzed most intensely in Wegener's granulomatosis (WG), where an expanded population of circulating CD4 + effector memory T-cells (CD4 + T EM ) was demonstrated. CD4 + T EM cells play a major role in the pathogenesis of several autoimmune diseases. Specific suppression of CD4 + T EM cells inhibits delayed-type hypersensitivity (DTH) and has therapeutic potential in autoimmune disease. Thus, CD4 + T EM cells may act as inducers of tissue injury and participate in the development of AAV. Therapies that target CD4 + T EM , without impairing the activity of other lymphocyte subsets, may hold therapeutic promise for AAV.
Renal IL-17 expression in human ANCA-associated glomerulonephritis
AJP: Renal Physiology, 2012
Interleukin-17A (IL-17) promotes inflammatory renal tissue damage in mouse models of crescentic glomerulonephritis, including murine experimental autoimmune anti-myeloperoxidase glomerulonephritis, which most likely depends on IL-17-producing Th17 cells. In human anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, however, the cellular sources of IL-17 remain to be elucidated. Therefore, we analyzed human kidney biopsies of active necrotizing and crescentic ANCA-associated glomerulonephritis by immunohistochemistry using an IL-17-specific antibody and by immunofluorescent colocalization with cell type markers. We detected numerous IL-17-expressing (IL-17+) cells in the glomeruli and in the tubulointerstitium. Unexpectedly, most of these IL-17+ cells were polymorphonuclear neutrophilic granulocytes, while IL-17+ T cells and IL-17+ mast cells were present at significantly lower frequencies. IL-17 was not detected in other infiltrating or resident kidney cells. I...
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2018
Early detection of renal involvement in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is of major clinical importance to allow prompt initiation of treatment and limit renal damage. Urinary soluble cluster of differentiation 163 (usCD163) has recently been identified as a potential biomarker for active renal vasculitis. However, a significant number of patients with active renal vasculitis test negative using usCD163. We therefore studied whether soluble CD25 (sCD25), a T cell activation marker, could improve the detection of renal flares in AAV. sCD25 and sCD163 levels in serum and urine were measured by enzyme-linked immunosorbent assay in 72 patients with active renal AAV, 20 with active extrarenal disease, 62 patients in remission and 18 healthy controls. Urinary and blood CD4+ T and CD4+ T effector memory (TEM) cell counts were measured in 22 patients with active renal vasculitis. Receiver operating characteristics (ROC) curves were generated and r...