Format

Send to

Choose Destination
Nephrology (Carlton). 2009 Feb;14(1):26-32. doi: 10.1111/j.1440-1797.2008.01069.x. Epub 2009 Jan 8.

Review article: The role of CD4(+) T cells in ANCA-associated systemic vasculitis.

Author information

1
Department of Rheumatology, University Medical Center Gronningen, The Netherlands. abdulahad@int.umcg.nl

Abstract

Antineutrophil cytoplasmic autoantibody (ANCA)-associated systemic vasculitis (AASV) constitutes a group of primary vasculitides associated with antineutrophil cytoplasmic autoantibodies, which are either directed to proteinase-3 or myeloperoxidase. In contrast to other forms of vasculitis, immuohistologic evaluation of affected tissues in patients with AASV, particularly the kidneys, demonstrated an absence or paucity of immunoglobulins, which could suggest involvement of cell-mediated injury in this disorder. Several studies have shed light on T cell-mediated immune responses playing a role in the pathophysiology of AASV. Imbalance of CD4(+) T-cell subsets has been demonstrated in the peripheral blood of patients with AASV. The trigger that leads to this imbalance remains to be defined, but clinical evidence shows that nasal carriage of Staphylococcus aureus constitutes a risk factor for disease exacerbation. Recent data show that superantigens and peptidoglycans from these Gram-positive bacteria can induce skewing of T-cell responses towards pathogenic interleukin (IL)-17-producing T-helper cells (Th17). Overproduction of IL-17 in response to this infection might aggravate inflammatory responses and contribute to the production of autoantibodies as well as to granuloma formation and tissue injury in patients with AASV. Next to Th17 cells, memory CD4(+) T cells with the effector cytotoxic phenotype (CD4(+) T(EM)) have also been demonstrated to constitute a major effector pathway of tissue injury in patients with pauci-immune glomerulonephritis. Therefore, future perspectives for treatment of AASV could be built on neutralization of IL-17 and depletion of CD4(+) T(EM) cells.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center