Cellular immunity in Wegener's granulomatosis: Characterizing T lymphocytes

Berden, Annelies E.; Kallenberg, Cees G. M.; Savage, Caroline O. S.; Yard, Benito A.; Abdulahad, Wayel H.; Heer, Emile de; Bruijn, Jan A.; Bajema, Ingeborg M.

doi:10.1002/art.24576

Cited by 56 publications

(39 citation statements)

References 90 publications

(128 reference statements)

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“…The granulomatous lesions suggest involvement of cellular immune responses in the pathogenesis of, particularly, WG. Indeed, activated T cells have been demonstrated in the peripheral blood of patients with WG, even during quiescent disease (reviewed by Berden et al 23 and Abdulahad et al 24). Their phenotype is that of effector memory T cells 23.…”

Section: In Vitro Studiesmentioning

confidence: 99%

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Pathogenesis of ANCA-associated vasculitides

Kallenberg

2011

Annals of the Rheumatic Diseases

141

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Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are characterised by necrotising inflammation of small vessels in conjunction with ANCA directed to either proteinase 3 (PR3) or myeloperoxidase (MPO). The aetiopathogenesis of these disorders is still not fully elucidated but clinical as well as in vitro and in vivo experimental data strongly suggest a role for the autoimmune responses to PR3 and MPO in disease development. Clinically, PR3-ANCA are strongly associated with granulomatous vasculitis as in Wegener's granulomatosis, and MPO-ANCA with necrotising small vessel vasculitis as in microscopic polyangiitis. Levels of PR3-ANCA and MPO-ANCA do, however, not fully reflect disease activity. In vitro, ANCA activate primed neutrophils to release lytic enzymes and reactive oxygen species, a process reinforced by the alternative pathway of complement. In the context of endothelial cells, this process leads to endothelial detachment and lysis. In vivo experimental studies have clearly demonstrated the pathogenic potential of MPO-ANCA for necrotising glomerulonephritis and pulmonary capillaritis. For PR3-ANCA-associated granulomatous vasculitis, an animal model is lacking. Here, effector T cells, in particular Th17 cells, appear to have a major pathogenic role in addition to ANCA. Finally, microbial factors, derived in particular from S aureus and Gram-negative bacteria, could play a part in disease induction and expression. These new insights into the pathogenesis of ANCA-associated vasculitides have opened new ways for targeted treatment.

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Section: In Vitro Studiesmentioning

confidence: 99%

“…Indeed, activated T cells have been demonstrated in the peripheral blood of patients with WG, even during quiescent disease (reviewed by Berden et al 23 and Abdulahad et al 24). Their phenotype is that of effector memory T cells 23. Surprisingly, percentages of these cells decreased in the peripheral blood during active disease.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Pathogenesis of ANCA-associated vasculitides

Kallenberg

2011

Annals of the Rheumatic Diseases

141

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“…Few studies demonstrate the presence of such cells at the vascular tissue sites, particularly in interstitial and periglomerular regions in kidney lesions (Cunningham et al 1999;Aasarod et al 2001;Weidner et al 2004). However most of the accumulating reports demonstrating an activated cell-mediated immunity focused on the abnormalities of peripheral lymphocytes (Berden et al 2009). Nevertheless, various experimental studies provided evidence for the role of Th1 lymphocyte response in mediating glomerular damage and crescent formation in ANCA-associated vasculitis (Holdsworth et al 1999).…”

Section: Anca-associated Vasculitismentioning

confidence: 96%

“…Additionally, a functional defect of the circulating T regulatory lymphocytes (T regs) was recently demonstrated in patients with WG, suggesting the implication of T regs abnormalities in the loss of immune homeostasis (Abdulahad et al 2007). However, the functional defect has been demonstrated in patients in remission and the effects of immunosuppressive therapies could not be excluded (Berden et al 2009). Yet, the implication of environmental and genetic factors in the loss of immune homeostasis and the outcome of the disease has been frequently suggested.…”

Section: Anca-associated Vasculitismentioning

confidence: 97%

Immunological Aspects of Systemic Vasculitis

Ahmed

Louzir

2011

Systemic Vasculitis

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“…The granulomatous inflammation observed in different tissues in WG/GPA suggests a strong role for the T-cell response, and both Th17 cells and regulatory T (Treg) cells are now receiving attention as potential players in disease development [28,34]. Other T-cell subtypes currently being investigated in the pathogenesis of AAV include CD8 + CD57 + and natural killler-like CD4 cells, but their role has not yet been clearly defined [35,36].…”

Section: Epidemiologymentioning

confidence: 99%