Decreases in the Numbers of Peripheral Blood Regulatory T Cells, and Increases in the Levels of Memory and Activated B Cells, in Patients with Active Eosinophilic Granulomatosis and Polyangiitis

Tsurikisawa, Naomi; Saitô, Hiroshi; Oshikata, Chiyako; Tsuburai, Takahiro; Akiyama, Kazuo

doi:10.1007/s10875-013-9898-x

Cited by 50 publications

(29 citation statements)

References 46 publications

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“…75 Conversely, a decreased percentage of CD4 + CD25 high FOXP3 + regulatory T cells has been demonstrated in patients with active EGPA, compared with patients with asthma or chronic eosinophilic pneumonia, 76 and decreases in regulatory T-cell numbers can further differentiate frequently-relapsing from seldom-relapsing EGPA. 77 …”

Section: Immunopathogenesis Of Egpamentioning

confidence: 99%

Eosinophils in vasculitis: characteristics and roles in pathogenesis

2014

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Eosinophils are multifunctional granular leukocytes that are implicated in the pathogenesis of a wide variety of disorders, including asthma, helminth infection, and rare hypereosinophilic syndromes. Although peripheral and tissue eosinophilia can be a feature of many types of small-vessel and medium-vessel vasculitis, the role of eosinophils has been best studied in eosinophilic granulomatosis with polyangiitis (EGPA), where eosinophils are a characteristic finding in all three clinical stages of the disorder. Whereas numerous studies have demonstrated an association between the presence of eosinophils and markers of eosinophil activation in the blood and tissues of patients with EGPA, the precise role of eosinophils in disease pathogenesis has been difficult to ascertain owing to the complexity of the disease process. In this regard, results of clinical trials using novel agents that specifically target eosinophils are providing the first direct evidence of a central role of eosinophils in EGPA. This Review focuses on the aspects of eosinophil biology most relevant to the pathogenesis of vasculitis and provides an update of current knowledge regarding the role of eosinophils in EGPA and other vasculitides.

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Section: Immunopathogenesis Of Egpamentioning

confidence: 99%

Eosinophils in vasculitis: characteristics and roles in pathogenesis

2014

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“…Ligation of CTLA-4 to CD80 or CD86 or both may trigger the IDO pathway in DCs, in turn activating the transcription factor FOXP3 (which regulates immune functioning) and inhibiting cytokine production by DCs [45]. We demonstrated that patients with EGPA who experience frequent relapses after initial clinical remission have decreased T reg cell counts; increased percentages of B cells positive for CD80, CD27, or CD95; lower CD19 + B cell counts; and lower serum IgG than do those who maintain remission [12]. In contrast, other patients never achieve clinical remission [12].…”

Section: Discussionmentioning

confidence: 99%

“…We demonstrated that patients with EGPA who experience frequent relapses after initial clinical remission have decreased T reg cell counts; increased percentages of B cells positive for CD80, CD27, or CD95; lower CD19 + B cell counts; and lower serum IgG than do those who maintain remission [12]. In contrast, other patients never achieve clinical remission [12]. These results suggest that an interaction between T reg cells and B cells via the overexpression of costimulatory molecules such as CD80 is related to EGPA disease severity.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with frequently relapsing EGPA, decreases in T reg cell numbers and increased percentages of activated B cells, such as CD80 + , CD27 + , and CD95 + B cells, may induce apoptosis of B cells [12]. T reg cells are involved in the etiology and mechanisms of EGPA, but their precise role is unknown, especially in relation to antigen-presenting cells such as dendritic cells (DCs).…”

Section: Introductionmentioning

confidence: 99%

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An increase of CD83+ dendritic cells ex vivo correlates with increased regulatory T cells in patients with active eosinophilic granulomatosis and polyangiitis

et al. 2014

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BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by the presence of allergic granulomatosis and necrotizing vasculitis with eosinophilic infiltration. The etiology of EGPA is unknown. Dendritic cells (DCs) are not only critical for the induction of primary immune responses; they may also be important for the induction of immunological tolerance and the regulation of the type of T-cell-mediated immune response. To investigate whether DC maturation is associated with EGPA disease status, we examined the relationship between the maturation of DCs and the differentiation of regulatory T (Treg) cells in EGPA patients. We exposed the CD14+ blood monocytes of 19 patients with EGPA in remission or relapse to stimulation with GM-CSF and IL-4 for 6 d and lipopolysaccharide for 24 h to obtain mature CD83+ DCs and immature CD206+ DCs. Using immunohistochemistry, we examined four patients for the presence of CD83+ and CD206+ DCs in the lung at the onset of EGPA.ResultsThe percentage of CD83+ cells among DCs differentiated from CD14+ monocytes was lower for EGPA patients in relapse than in remission. The percentage of CD83+ DCs was inversely correlated with the percentage of CD206+ DCs and was significantly correlated with the numbers of naturally occurring CD4+ regulatory Treg (nTreg; FOXP3+CD4+) cells and inducible Treg (iTreg; CD4+CD25+ T cells producing IL-10 or TGF-β) cells but not the number of eosinophils. The percentage of CD206+ DCs was significantly inversely correlated with the percentages of nTreg and iTreg cells but not the number of eosinophils. Immunohistochemistry revealed both CD206+ DCs and CD83+ DCs in alveoli and interstitial spaces at the onset of EGPA.ConclusionThe maturation of DCs from monocytes was related to disease activity in patients with EGPA. Increased CD83+ DCs in EGPA patients may induce the differentiation of iTreg and nTreg cells, thereby suppressing inflammation and disease activity.

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“…Moreover, several lines of evidence also point to a role of B lymphocytes and humoral responses as further contributing to EGPA pathogenesis. Increase in the levels of activated and memory B cells have been found in active EGPA [15]. Myeloperoxidase (MPO)-pANCA are present in 40% of untreated patients [2].…”

Section: Editorialmentioning

confidence: 99%

Immunotherapy in Eosinophilic Granulomatosis with Polyangiitis: A New Step Forward?

Puéchal¹

2016

J Vasc

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Decreases in the Numbers of Peripheral Blood Regulatory T Cells, and Increases in the Levels of Memory and Activated B Cells, in Patients with Active Eosinophilic Granulomatosis and Polyangiitis

Abstract: In patients with frequently relapsing EGPA, decreases in Treg cell numbers and increased percentages of activated B cells may induce apoptosis of B cells.

Cited by 50 publications

References 46 publications

Eosinophils in vasculitis: characteristics and roles in pathogenesis

Eosinophils in vasculitis: characteristics and roles in pathogenesis

An increase of CD83+ dendritic cells ex vivo correlates with increased regulatory T cells in patients with active eosinophilic granulomatosis and polyangiitis

Immunotherapy in Eosinophilic Granulomatosis with Polyangiitis: A New Step Forward?

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