Granuloma formation in ANCA-associated vasculitides. APMIS Suppl

Department of Rheumatology, Vasculitis Center UKSH & Klinikum Bad Bramstedt, University of Lübeck, Lübeck, Germany.
APMIS. Supplementum 06/2009; 117(127):32-6. DOI: 10.1111/j.1600-0463.2009.02474.x
Source: PubMed


Granuloma formation is a key pathologic finding in two of the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides: Wegener's granulomatosis (WG) and Churg-Strauss syndrome (CSS). So far, no animal models have been established convincingly reproducing both vasculitic and granulomatous features typical of WG and CSS. In biopsies, granulomatous lesions are found both at distant extravascular sites and in the vicinity of inflamed vessels, e.g. in the lung. Intriguingly, WG-granulomata appear to display features of tertiary lymphoid tissue. Cartilaginous and osseous destruction is caused by granulomatous inflammation invading adjacent tissues. Rhinosinusitis is regularly encountered in WG and CSS. Septal perforation, saddle nose deformity, middle and inner ear symptoms, and granulomatous invasion of the palate, orbita, meninges, or the pituitary gland may complicate WG. Both common (e.g. FCGR3B copy number) and distinct (e.g. HLA-DP, IL-10.2) genetic factors have been identified in AAV potentially favouring inflammation and autoimmunity. The HLA-DPB1/RING1/RXRB region constitutes a quantitative trait locus for ANCA-positive WG with the strongest association to be reported up to now. A profound alteration of the T-cell response including Th1 and Th17 responses, anomalously NK-receptor-expressing 'NK-like' T cells, and dysfunctional regulatory T cells could facilitate and sustain granuloma formation and autoimmunity.

Download full-text


Available from: Peter Lamprecht, Jul 23, 2015
  • Source
    • "Granuloma formation is a key pathologic finding in two of the ANCA-associated vasculitides: GPA and EGPA [14]. It is suggested that PR3 (and possibly also MPO) displays features of an endogenous “danger signal” inducing autoinflammation [14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A 70-year-old man was admitted to our hospital because of weight loss and persistent dry cough. Chest radiograph and CT showed multiple infiltrates in the bilateral upper lobes and the remarkably thickened bronchial walls. Bronchoscopy revealed diffuse erythema and edema of the tracheobronchial mucosa without any ulcerous legions. Serum MPO-ANCA was positive (155 EU). Transbronchial biopsy was performed and revealed necrotic granulomas with multinucleated giant cells in the bronchial/bronchiolar and parenchymal lesions. Thus, we diagnosed it as a localized form of granulomatosis with polyangiitis (GPA, Wegener's granulomatosis). After treatment with corticosteroid and cyclophosphamide, the bronchial findings were entirely resolved. We report here a rare case of GPA presenting with markedly inflamed tracheobronchial mucosa.
    Full-text · Article · Sep 2013 · Case Reports in Medicine
  • Source
    • "Renal survival at 1 year for the focal, mixed, crescentic and sclerotic class was 100%, 86%, 72% and 61% respectively. These data show a significant difference between the classes, however, the phenotypical order of the classes is different compared to the original validation study, but similar to the results demonstrated by the Japanese [3] and Chinese [2] investigators. In all but the original study, patients with crescentic class biopsies show better outcome than those with mixed class biopsies. "

    Full-text · Article · Feb 2013 · La Presse Médicale
  • Source
    • "Indeed, Abdulahad et al. [35] described increased levels of effector memory T cells in the peripheral blood of patients with WG during remission. Immune effector cells have been observed in granulomatous tissue in patients with AAV [36]. Surprisingly, effector memory cells disappeared from the peripheral blood during active disease in AAV. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Antineutrophil cytoplasmic autoantibodies (ANCAs) directed to proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are strongly associated with the ANCA-associated vasculitides--Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical observations, including the efficacy of B-cell depletion via rituximab treatment, support--but do not prove--a pathogenic role for ANCA in the ANCA-associated vasculitides. In vitro experimental studies show that the interplay of ANCA, neutrophils, the alternative pathway of the complement system, and endothelial cells could result in lysis of the endothelium. A pathogenic role for MPO-ANCA is strongly supported by in vivo experimental studies in mice and rats, which also elucidate the pathogenic mechanisms involved in lesion development. Unfortunately, an animal model for PR3-ANCA-associated Wegener's granulomatosis is not yet available. Here, cellular immunity appears to play a major role as well, particularly via interleukin-17-producing T cells, in line with granulomatous inflammation in the lesions. Finally, microbial factors, in particular Staphylococcus aureus and gram-negative bacteria, seem to be involved in disease induction and expression, but further studies are needed to define their precise role in disease development.
    Full-text · Article · Sep 2010 · Current Rheumatology Reports
Show more