Localized Wegener's granulomatosis: predominance of CD26 and IFN-γ expression

• Published in: The Journal of pathology 2000-09, Vol.192 (1), p.113-120
• Main Authors: Müller, Antje, Trabandt, Andreas, Gloeckner-Hofmann, Katharina, Seitzer, Ulrike, Csernok, Elena, Schönermarck, Ulf, Feller, Alfred C., Gross, Wolfgang L.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Biopsy; CD26; Cell Culture Techniques; Dipeptidyl Peptidase 4 - metabolism; Female; Gene Expression; granuloma; Granulomatosis with Polyangiitis - immunology; Granulomatosis with Polyangiitis - pathology; Humans; IFN-γ; Immunoenzyme Techniques; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin-10 - biosynthesis; Interleukin-10 - genetics; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; localized Wegener's granulomatosis; Male; Medical sciences; Middle Aged; Nasal Mucosa - metabolism; Nasal Mucosa - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/1096-9896(2000)9999:9999<::AID-PATH656>3.0.CO;2-M

The immune response in Wegener's granulomatosis (WG) has been characterized as a predominant, potentially pathogenic Th1‐like reaction by blood T cells and T‐cell clones from diseased tissues. To elucidate further the immunopathogenic mechanisms, this study analysed the phenotypes of inflammatory infiltrates in frozen nasal biopsies with involvement of the upper respiratory tract only (localized or ‘initial phase’ WG) and with multi‐organ involvement, including systemic vasculitis (generalized WG). The expression and production of Th1 and Th2 cytokines were examined in tissue specimens and peripheral blood mononuclear cells (PBMCs) of localized and generalized WG. The number of CD3+ T cells in inflammatory infiltrates ranged from 50 to 70%, together with approximately 30% CD14+ monocytes/macrophages. An average of 40% of T cells expressed CD26 in nasal biopsies of localized WG, compared with about 16% in specimens of generalized WG. In parallel, a higher number of interferon‐γ (IFN‐γ)‐positive cells were detected in nasal tissue of localized than in generalized WG. PBMCs from localized WG similarly exhibited higher spontaneous IFN‐γ production in contrast to generalized WG (207 vs. 3 pg/ml, p