Patients with Wegener’s granulomatosis demonstrate a relative deficiency and functional impairment of T‐regulatory cells

Abstract

Summary An increased proportion of CD4+ CD25+ T cells has been reported in Wegener’s granulomatosis (WG) and may represent an accumulation of regulatory T cells (Treg). CD25 is also expressed on recently activated effector T cells. We have determined the relative proportion of these subsets in a large patient cohort. The fraction of Treg in peripheral blood mononuclear cells from patients and healthy controls was determined by assessment of Foxp3 expression on CD4+ CD25+ T cells. The functional activity of Treg was determined by their ability to suppress proliferation and cytokine production in response to proteinase‐3. Although WG patients demonstrated an increased fraction of CD4+ CD25+ T cells, the percentage of Foxp3‐positive cells was decreased. In addition, the percentage of Treg was inversely related to the rate of disease relapse. CD4+ CD25hi T cells were able to suppress T‐cell proliferation to proteinase‐3 in healthy controls and anti‐neutrophil cytoplasm antibody (ANCA)‐ negative patients (at time of sampling) but not in ANCA‐positive patients. In patients with active disease, an increased proportion of CD4+ Foxp3+ cells was associated with a more rapid disease remission. Patients with WG demonstrate abnormalities in the number and function of Treg and this is most pronounced in those with most active disease. This information is of value in understanding the pathogenesis and potential treatment of this disease.

Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen species

“…Recently, a role for Treg in granuloma clearing was described in Wegener's granulomatosis. Treg number and function were reduced in patients with this disease, and the reduction was most pronounced in subjects with most active disease (48).…”

A case of (double) ANCA-negative granulomatosis with polyangiitis (Wegener’s)

“…T cells); CD4 ? CD25 hi T cells were able to suppress T-cell proliferation to PR3 in healthy controls and ANCA-negative patients but not in ANCA-positive patients [15]. A skewed response of an interleukin-17-producing T-helper cell lineage (Th17) found in patients with ANCA-positive GPA following stimulation with the autoantigen PR3 suggests that interleukin-17 is involved in disease pathogenesis [16].…”

Diagnostic and management challenges in Goodpasture’s (anti-glomerular basement membrane) disease

“…The role of regulatory T cells in maintaining and re-stablishing immune tolerance to the autoantigen has been suggested as a reason for lack of disease in healthy individuals and paucity of relapses in treated anti-GBM (38) , unlike that found in ANCA vasculitis where regulatory cell deficiencies have been identified (39,40). In keeping with this concept, depletional biologic agents that can effectively remove all T cell subsets (Alemtuzumab, anti-CD52) have been found to trigger de-novo anti-GBM disease (41,42).…”