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

Müller, Antje; Trabandt, Andreas; Gloeckner-Hofmann, K.; Seitzer, Ulrike; Csernok, Elena; Schönermarck, Ulf; Feller, Alfred C.; Gross, Wolfgang L.

doi:10.1002/1096-9896(2000)9999:9999<::aid-path656>3.3.co;2-d

Cited by 14 publications

(19 citation statements)

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“…An important reason for this difference between our two studies could be the expression of IFN-g by mononuclear cell populations other than T cells, such as natural killer (NK) cells and monocyte/macrophages [23]. Similar to our observation, an increased IFN-g mRNA expression has been reported in the lesions of giant cell arteritis (GCA) [24] and in the lesions as well as PBMCs of patients with Wegener's granulomatosis (WG) [25]. The data available on IL-2 in TA is contradictory.…”

Section: Discussionsupporting

confidence: 73%

Cytokine mRNA repertoire of peripheral blood mononuclear cells in Takayasu's arteritis

Tripathy¹,

Chauhan

Nityanand

2004

Clinical and Experimental Immunology

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SUMMARYWe have investigated constitutive and phytohaemagglutinin (PHA) + phorbol 12-myristate 13-acetate (PMA)-induced gene expression of tumour necrosis factor (TNF)-a , interferon (IFN)-g , interleukin (IL)-2, IL-3, IL-4, IL-10, IL-12 and granulocyte macrophage colony-stimulating factor (GM-CSF) in peripheral blood mononuclear cells (PBMCs) of 10 patients with Takayasu's arteritis (TA) and 10 healthy controls by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). The constitutive mRNA expression of TNF-a (69·0 ± 4·0% versus 27·5 ± 18·0%; P = 0·001) and IL-4 (60·0 ± 10·0% versus 0%; P = 0·001) was significantly higher in patients than controls; that of IL-3 was comparable in both groups (38·0 ± 6·0% versus 32·0 ± 5·0%; P = 0·651) while no constitutive mRNA expression was observed for the other cytokines studied. The stimulated PBMCs of patients, as compared with the controls, had higher mRNA gene expression of TNF-a (127·0 ± 16·0% versus 54·0 ± 6·0%; P = 0·001), IFN-g (93·0 ± 13·0% versus 57·0 ± 5·0%; P = 0·032), IL-2 (109·0 ± 13·0% versus 68·0 ± 6·0%; P = 0·015), IL-3 (60·0 ± 8·0% versus 21·2 ± 3·0%; P = 0·045) and IL-4 (68·0 ± 7·0% versus 27·0 ± 7·2%; P = 0·01) The mRNA expression of IL-10 was lower in patients than controls (35·0 ± 8·0% versus 75·0 ± 12·0%; P = 0·022). The GM-CSF mRNA was similar (102·0 ± 6·0% versus 89·0 ± 5·0%; P = 0·475) in both groups. Stimulation of cells with PHA + PMA showed no IL-12 expression but stimulation with lipopolysaccharide induced higher IL-12 mRNA in patients than controls (83·0 ± 14·0% versus 33·0 ± 4·0%; P = 0·005). Our data suggest that an inflammatory cytokine signature exists in TA with a key role for TNF-a , IL-4, IL-10 and IL-12 in different pathological processes of the disease.

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Section: Discussionsupporting

confidence: 73%

Cytokine mRNA repertoire of peripheral blood mononuclear cells in Takayasu's arteritis

Tripathy¹,

Chauhan

Nityanand

2004

Clinical and Experimental Immunology

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“…The cytokine profile of mononuclear cells (high IFN-␥, IL-12, and TNF␣, which is suppressed by IL-10) in the blood and affected tissues of patients with ANCA-associated GN is consistent with a Th1 response (77). The phenotype of T cells from blood, bronchial lavage, and nasal biopsy specimens of patients with Wegener's granulomatosis also is consistent with Th1-driven cell-mediated immunity (78,79). Immunohistochemistry of affected tissues also demonstrates the presence of IFN-␥ (79) and IL-8 (79,80).…”

Section: T Cells In Anca-associated Crescentic Gnmentioning

confidence: 73%

“…The phenotype of T cells from blood, bronchial lavage, and nasal biopsy specimens of patients with Wegener's granulomatosis also is consistent with Th1-driven cell-mediated immunity (78,79). Immunohistochemistry of affected tissues also demonstrates the presence of IFN-␥ (79) and IL-8 (79,80). However, these observations are not uniform, and predominance of CD3 ϩ cells, eosinophils, and Th2 cytokines has been reported in a study of nasal biopsies from patients with Wegner's granulomatosis (81).…”

Section: T Cells In Anca-associated Crescentic Gnmentioning

confidence: 74%

T Cells in Crescentic Glomerulonephritis

Tipping

Holdsworth

2006

Journal of the American Society of Nephrology

160

150

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G lomerulonephritis (GN) is not a single disease but shows a variety of histologic patterns, clinical features, and outcomes that indicate multiple pathogenic mechanisms. A pivotal role for adaptive immune responses in initiation of GN has been demonstrated in experimental models, but across the spectrum of human GN, direct evidence of immune pathogenesis is more variable. The strongest case that adaptive immune responses drive nephritogenic events in glomeruli in humans has been mounted in crescentic GN, and evidence for involvement of autoimmunity, either organspecific autoimmunity to glomerular antigens (e.g., anti-glomerular basement membrane [anti-GBM] GN) or systemic autoimmunity to nonglomerular antigens (e.g., ANCA-associated crescentic GN, lupus nephritis) now is emerging for many forms of human crescentic GN. CD4 ϩ T cells play a central role in adaptive immunity. T cell-independent responses are uncommon. They usually are associated with simple carbohydrate-rich antigens and do not show extensive Ig isotype switching or strong affinity maturation. The known antigens that drive crescentic GN show strong evidence of CD4 ϩ T cell dependence and do not have the characteristics of T-independent antigens. The evidence from glomerular pathology also suggests a prominent role for local CD4 ϩ T cell-driven Th1-type responses in crescentic GN with delayed-type hypersensitivity (DTH)-like cellular effectors (T cells and macrophages) as well as Th1 Ig isotypes in glomeruli.The relative contributions of cellular and humoral CD4 ϩ T cell-driven effectors, particularly in ANCA-associated GN, remains controversial, but it is clear that the nephritogenic immune responses are CD4 ϩ T cell-driven.

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“…In an examination of nasal biopsy specimens, Müller et al (40) noted differences in cytokine expression across the localized and generalized disease subsets. Balding et al (41) detected a Th2 response within nasal biopsy specimens obtained from patients with WG but noted that this bias appeared to be lost in both renal biopsy samples and among circulating T cells that responded to proteinase 3.…”

Section: Discussionmentioning

confidence: 99%

Limited versus severe Wegener's granulomatosis: Baseline data on patients in the Wegener's granulomatosis etanercept trial

Stone¹

2003

Arthritis & Rheumatism

359

153

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Objective. To report baseline data on 180 patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET), and to examine demographic and clinical differences between patients with limited disease and those with severe disease.Methods. Definitions of limited and severe disease were agreed upon by consensus of the investigators at a pretrial meeting and were incorporated into the protocol as a stratification criterion. These data were applied prospectively to the WGET patient cohort, based on clinical features and the intention to treat patients according to disease activity. Data related to disease onset, date of diagnosis, clinical features, antineutrophil cytoplasmic antibody assays, tissue biopsy findings, and other medical history were collected on a baseline medical history form. Physician-investigators from each center participated in the development of this form, and all were certified in its use prior to the start of the trial. Selected data on patients who were screened for the trial but were not enrolled were also collected.Results. Several significant differences between the limited and severe disease subsets were observed. Patients with limited disease were nearly a decade younger at disease onset compared with patients with severe disease. Thirty-three percent of patients with severe disease were women, compared with 58% of those with limited disease. Despite their younger age at symptom onset, patients with limited disease tended to have longer disease duration, a greater likelihood of experiencing exacerbation of previous disease following a period of remission, and a higher prevalence of destructive upper respiratory tract disorders at the time of enrollment (e.g., saddle-nose deformity). Patients with limited WG were less likely than those with severe disease to have antibodies to either proteinase 3 or myeloperoxidase. Patients with severe disease had a higher likelihood of previous thyroid disease, particularly either Graves' disease or Hashimoto thyroiditis, suggesting the possibility of different pathogenetic factors within these disease subsets. Other observed differences between these subsets, such as the greater frequency of alveolar hemorrhage in the severe disease group, were related to the a priori definitions of limited and severe disease.Conclusion. There are significant differences between patients with limited WG and those with severe WG with regard to sex, age, the likelihood of recurrent disease, the risk of damage in certain organ systems, and, possibly, etiologic factors. These differences (and perhaps other differences that are currently unrecognized) in patient subsets may have implications for mechanisms of pathogenesis, prognosis, response to treatment, and the design of future clinical investigations.

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

Cited by 14 publications

References 0 publications

Cytokine mRNA repertoire of peripheral blood mononuclear cells in Takayasu's arteritis

Cytokine mRNA repertoire of peripheral blood mononuclear cells in Takayasu's arteritis

T Cells in Crescentic Glomerulonephritis

Limited versus severe Wegener's granulomatosis: Baseline data on patients in the Wegener's granulomatosis etanercept trial

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