Abnormalities of CD4+ T cell subpopulations in ANCA-associated vasculitis

Marinaki, Smaragdi; Neumann, Irmgard; Kälsch, Anna-Isabelle; Grimminger, Peter P.; Breedijk, Annette; Birck, Rainer; Schmitt, Wilhelm H.; Waldherr, Rüdiger; Yard, Benito A.; Woude, Fokko J. van der

doi:10.1111/j.1365-2249.2005.02731.x

Cited by 60 publications

(58 citation statements)

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“…These abnormalities include lymphopenia [15], a high number of activated T lymphocytes in peripheral blood [16], skewing of Th1 to Th2 responses [17] and senescence of CD28 -lymphocytes in the CD8 + subpopulation [18]. Our results also demonstrate beneficial effects of DSG on T cells by inhibiting T cell receptor-mediated T cell proliferation and cytokine production in both Th1 and Th2 T cells.…”

Section: Discussionsupporting

confidence: 62%

In vivoeffects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis

Kälsch

Schmitt

Breedijk

et al. 2006

Clinical and Experimental Immunology

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Summary 15-Deoxyspergualin (DSG)is an alternative treatment modality for Wegener's granulomatosis (WG) patients refractory to conventional treatment. Nevertheless, it is unclear how DSG modulates disease activity in these patients. This study was conducted to investigate which parameters of adaptive and acquired immunity were influenced during two subsequent cycles of DSG treatment. Emphasis was put upon T cell and monocyte activation, neutrophil function and surface expression of proteinase-3 (PR-3). Anti-CD3/anti-CD28 and interleukin (IL)-15/IL-7-mediated T cell proliferation were assessed by fluorescence activated cell sorter (FACS) analysis using carboxyfluorescein succinimidyl ester (CSFE) labelling. Interferon (IFN)-g and IL-10 production were determined in the supernatants of these cultures by enzyme-linked immunosorbent assay. Monocyte activation was assessed in lipopolysaccharide (LPS)-stimulated whole blood, using tumour necrosis factor (TNF)-a as read-out. Neutrophil function was determined by measuring oxidative burst, chemotaxis and phagocytosis. T cell activation markers and PR3 expression were measured by FACS. All parameters were determined directly before and after each DSG cycle. Anti-CD3/anti-CD28-mediated T cell proliferation was reduced directly after DSG treatment. Directly before a subsequent cycle of DSG was started, T cell proliferation was increased. Similar findings were observed for IFN-g and IL-10 production by T cells. DSG did not influence IL-15/IL-7-mediated T cell proliferation. LPS-mediated TNF-a production was also impaired directly after DSG treatment. No influence on T cell activation markers, neutrophil function and surface PR-3 expression was observed in peripheral blood of these patients. Our data demonstrate that DSG influences T cell and monocyte activation in a reversible fashion. Although DSG causes neutropenia in these patients, it does not influence neutrophil function.

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Section: Discussionsupporting

confidence: 62%

In vivoeffects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis

Kälsch

Schmitt

Breedijk

et al. 2006

Clinical and Experimental Immunology

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“…Louthrenoo et al (2) reported a low CD4/CD8 lymphocyte ratio in three of the six patients with KS and rheumatic disease. In total lymphocyte numbers and absolute/relative numbers of CD4 T-helper cells are low in patients with GPA compared with controls, irrespective of the disease activity (11). Therefore, low CD4-T helper state may play an important role in the pathogenesis of KS development.…”

Section: Discussionmentioning

confidence: 97%

Kaposi’s sarcoma concurrent with granulomatosis polyangiitis

et al. 2016

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“…These T-cells subsets are activated T-cells as well as Tregs (regulatory T cells) (38). Abdulahad et al reported an increase of CD25 high (Treg) CD4 T cells and CD25 low (activated T effector cells) cell populations in patients with Wegener's granulomatosis.…”

Section: Implications Of T-cell Immunity As Lesional and Circulatory mentioning

confidence: 99%

“…Circulating CD4+ CD25 T-cell population increases in AAV (36)(37)(38)(39). These T-cells subsets are activated T-cells as well as Tregs (regulatory T cells) (38).…”

Section: Implications Of T-cell Immunity As Lesional and Circulatory mentioning

confidence: 99%

Recent Aspects of Vasculitis and Future Direction

Aras

2011

Intern. Med.

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Vasculitis is pathologically identified as specific cellular inflammation, vessel destruction, and tissue necrosis. Current classifications of vasculitis such as the Chapel Hill Classification (CHCC) and American College of Rheumatology (ACR) guidelines are not sufficiently adequate for clinicians to diagnose vasculitis. The biomarkers that are currently in clinical use such as PR3-ANCA and MPO-ANCA, only help in diagnosing small vessel vasculitis and their sensitivity and specificity are not sufficient. However, recent developments related to the pathogenesis and etiopathogenesis of vasculitis have the potential to contribute to new and improved biomarkers. The determination of diverse roles of ANCA and synergistic effects of infection, genetic, environmental factors and drugs on pathogenesis is quite important. The demonstration of a new autoantibody directed to hLAMP-2 and the resemblance to some microbial structures, in addition to the determination of the possible roles of hepatitis B and C on vasculitis are important findings. These hints may lead to new biomarker developments, providing a better method to diagnose vasculitis. The evidence on T cell immunity as circulatory and lesional will likely contribute to the development of new drugs for vasculitis.

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Abnormalities of CD4+ T cell subpopulations in ANCA-associated vasculitis

Abstract: Summary In patients with ANCA-associated vasculitis (AAV), CD25 expression is increased on circulating T cells. Although in animal experiments the role of CD4+

Cited by 60 publications

References 34 publications

In vivoeffects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis

In vivoeffects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis

Kaposi’s sarcoma concurrent with granulomatosis polyangiitis

Recent Aspects of Vasculitis and Future Direction

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