Therapeutisches Vorgehen bei ANCA-assoziierten Vaskulitiden

Hellmich, Bernhard

doi:10.1007/s00393-014-1532-7

Cited by 3 publications

(2 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Medical records from all patients from cohorts I and II were (re-)analyzed. To best reflect clinical activity, the definitions of GPA activity states from current recommendations for clinical studies [ 16 – 19 ] were slightly adapted and applied as follows: remission on drug - inactive disease, absence of symptoms for at least 6 months, prednisone intake <10 mg/day; remission off drug - inactive disease, absence of symptoms, no disease-modifying antirheumatic drug (DMARD) intake for at least 6 months. By definition, the Birmingham vasculitis activity score (BVAS) had to be 0 to identify remission; response was defined as BVAS reduction >50 % compared to the last clinical visit; refractory disease was defined as no response after 6 weeks of treatment or progressive disease after 4 weeks of treatment, or chronically persisting activity with one major or three minor BVAS items; grumbling disease was defined as minor, non-organ-threatening symptoms that usually respond to elevation of prednisone doses or DMARDs (e.g.…”

Section: Methodsmentioning

confidence: 99%

Active but not inactive granulomatosis with polyangiitis is associated with decreased and phenotypically and functionally altered CD56dim natural killer cells

et al. 2016

View full text Add to dashboard Cite

BackgroundThe role of natural killer (NK) cells in granulomatosis with polyangiitis (GPA) is poorly understood. We recently reported that peripheral blood NK cell percentages correlate with the suppression of GPA activity (cohort I). The purpose of the current study was to further characterize NK cell subsets, phenotype and function in a second GPA cohort (cohort II).MethodsPeripheral blood lymphocyte subsets were analyzed at a clinical diagnostic laboratory. Clinical data were extracted from medical records and patients were grouped according to their activity state (remission vs. active/non-remission). Separate analysis (cohort II, n = 22) and combined analysis (cohorts I and II, n = 34/57) of NK cell counts/percentages was performed. NK cell subsets and phenotypes were analyzed by multicolor flow cytometry. Cytotoxicity assays were performed using 51Cr-labeled K562 target cells.ResultsIn cohort II, NK cell counts were lower than the lower limit of normal in active GPA, despite normal percentages due to lymphopenia. NK cell counts, but not other lymphocyte counts, were significantly higher in remission. Combined analysis of cohorts I and II confirmed decreased NK cell counts in active GPA and increased percentages in long-term remission. Follow-up measurements of six patients revealed increasing NK cell percentages during successful induction therapy. Multicolor analysis from cohort II revealed that in active GPA, the CD56dim subset was responsible for decreased NK cell counts, expressed more frequently CD69, downregulated the Fc-receptor CD16 and upregulated the adhesion molecule CD54, the chemokine receptor CCR5 and the activating receptor NKG2C. In remission, these markers were unaltered or marginally altered. All other receptors investigated (NKp30, NKp44, NKp46, NKG2D, DNAM1, 2B4, CRACC, 41BB) remained unchanged. Natural cytotoxicity was not detectable in most patients with active GPA, but was restored in remission.ConclusionsNK cell numbers correlate inversely with GPA activity. Reduced CD56dim NK cells in active GPA have an activated phenotype, which intriguingly is associated with profound deficiency in cytotoxicity. These data suggest a function for NK cells in the pathogenesis and/or modulation of inflammation in GPA. NK cell numbers, phenotype (CD16, CD69, NKG2C) or overall natural cytotoxicity are promising candidates to serve as clinical biomarkers to determine GPA activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1098-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

Active but not inactive granulomatosis with polyangiitis is associated with decreased and phenotypically and functionally altered CD56dim natural killer cells

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Immunsuppressiva sollten auch zum Einsatz kommen bei leichten Verläufen mit initialer GK-Monotherapie und fehlendem Therapieansprechen in 4 Wochen[22,23].Zur Remissionsinduktion bei ANCA-assoziierten Vaskulitiden im Generalisationsstadium mit Lebens-bzw. Organbedrohung wird neben Cylophosphamid-Puls-Therapie nach dem CYCLOPS-Protokoll nach optionalem initialen Methylprednisolon-Puls eine GK-Dosis von 1 mg/kg/d Prednisolonäquivalent eingeleitet, welche innerhalb von 3 Monaten auf ≤ 10 mg/d reduziert werden soll[24,25].Bei eosinophiler Granulomatose mit Polyangiitis mit Organ-u./o. Lebens-bedrohenden Manifestationen wird additiv zur Cylophosphamid-Puls-Therapie nach dem CYCLOPS-Protokoll ebenfalls Prednisolon eingesetzt.…”

unclassified

Prophylaxe und Therapie der Glukokortikoid-induzierten Osteoporose

Oelzner

Wolf

2017

Akt Rheumatol

View full text Add to dashboard Cite

ZusammenfassunGDie Glukokortikoid-induzierte Osteoporose (GK-OP) ist eine der häufigsten Formen der Osteoporose. Epidemiologischen Untersuchungen zufolge nehmen 0,5-0,9 % der Bevölkerung Glukokortikoide (GK) ein, bei den über 50-jährigen liegt diese Zahl bei ca. 3 %. Das Frakturrisiko ist unter chronischer GKTherapie auf das Doppelte erhöht und liegt auf Grund der bevorzugten Wirkung von GK auf den trabekulären Knochen für Wirbelkörperfrakturen noch höher. Pathogenetisch liegt der GK-OP eine Verminderung von Knochenmasse und -qualität zugrunde, welche aus suppressiven Effekten von GK auf die Zahl Übersichtsarbeit abstr ac t Glucocorticoid-induced osteoporosis (GC-OP) is one of the most frequent forms of osteoporosis. Based on epidemiological investigations, 0.5-0.9 % of the community population use oral glucocorticoids (GC); in persons aged 50 or more, the number of GC users is about 3 %. The fracture risk is increased twofold in patients with chronic GC treatment and is even higher for vertebral fractures because GCs predominantly affect trabecular bone. The pathogenetic origin of GC-OP is a loss of bone mass and quality resulting from the suppressive effects of GC on the number and function of osteoblasts and osteocytes and an increase in bone resorption. Systemic effects inducing sarcopenia with an increased risk of falls, hormonal changes and a negative calcium balance may further amplify the unfavourable effects of GCs on bone. Basic diagnostic evaluation for osteoporosis including osteodensitometry is indicated when GC treatment with a minimum daily dose of 2.5 mg/d prednisolone equivalent is planned for more than 3 months. The fracture risk is already increased in the first 3 months of GC treatment. Therefore an early intervention to prevent GC-induced loss of bone mass is necessary. The guidelines given by the umbrella organisation of the German osteology societies provide the foundation for prophylaxis and treatment of GC-OP based on the calculated fracture risk. General measures include the prevention of falls and improvement of muscle mass and coordination as well as a sufficient supply of calcium and vitamin D. The indication for specific drug treatment exceeding these basic measures depends on the individual fracture risk, which is determined by daily GC dose, duration of GC treatment, age, gender and other risk factors including the underlying disease that is treated with GC. For the implementation of the recommendations, particularly in the prophylactic approach, the calculation of the duration and dose of planned GC treatment is essential. In this context the guidelines for treatment of the different inflammatory rheumatic diseases provide crucial orientation. Treatment with GC doses of ≥ 7.5 mg/d prednisolone equivalent for more than 3 months requires specific drug treatment if T scores are < − 1.5 or if low-traumatic vertebral fractures or multiple peripheral fractures are present. GC doses between 2.5 und 7.5 mg/d require a lowering of the treatment threshold, which is determined by age, gende...

show abstract