Background Tissue destruction of the upper respiratory tract related to Granulomatosis with Polyangiitis (Wegener’s) – (GPA) which may result in stigmatizing lesions of the face is still poorly understood. Nasal biopsies that contain cartilage and/or bone to study the destruction process are difficult to obtain. Recent findings in a xenograft model of GPA in immunodeficient mice suggest that fibroblasts mediate at least in part this destruction of cartilage.
Objectives To compare morphological and immunohistochemical features of destruction in GPA patients and GPA tissues xenografted into immunodeficient mice.
Methods Nasal biopsies from GPA patients containing cartilage and/or bone fragments were evaluated for destruction by conventional histology. Cellular components, markers of differentiation and proliferation were characterized by immunohistochemistry (vimentin, CD68, TRAP, MMP 1-3-13, ALP, Osteonectin, CD 31, Ki-67). Xenografts of nasal mucosa from GPA patients with active endonasal disease and from sinusitis control patients were co- transplanted with healthy human cartilage in immunodeficient pfp/rag2 -/- mice and were investigated in parallel.
Results Samples of nasal biopsies from GPA patients as well as xenografted GPA tissues show GPA related cartilage/bone destruction mediated by invading cells, not by ischemic necrosis due to vasculitis or areactive geographical necrosis. Invading cells in xenografts were identified as predominantly human fibroblast, while human tissues showed a more complex and variable pattern of cartilage/bone destruction. However, the morphology of destruction was very similar in tissue samples from both sources.
Conclusions Nasal cartilage/bone destruction in GPA is an active process related to a broad spectrum of cells. However, fibroblasts are the dominant cartilage destructing cells both in GPA patients and in GPA xenografts, thus validating the findings in xenografts to be relevant for the human pathophysiology.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.