IntroductionThe role of CD3−CD56+ natural killer (NK) cells in granulomatosis with polyangiitis (GPA) is poorly understood. Recently, it has been shown that peripheral blood NK cells can kill renal microvascular endothelial cells, suggesting a pathogenic role of NK cells in this disease. So far, subset distribution, phenotype, and function of peripheral blood NK cells in relation to GPA disease activity have not been elucidated. Moreover, it is not known whether NK cells infiltrate GPA tissue lesions.MethodsParaffin sections of GPA granulomas and controls were stained with anti-CD56 and anti-CD3 antibodies. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. NK cell degranulation was analyzed using cocultures of patient PBMCs with target cells and surface expression of CD107a. Clinical data were extracted from medical records. Statistical analysis was performed in an exploratory way.ResultsCD56+ cells were not detectable in active granulomatous GPA lesions but were found frequently in granulomas from tuberculosis and sarcoidosis patients. In GPA, the proportion of NK cells among peripheral blood lymphocytes correlated negatively with the Birmingham Vasculitis Activity Score (BVAS) (n = 28). Accordingly, NK cell percentages correlated positively with the duration of remission (n = 28) and were significantly higher in inactive GPA (BVAS = 0, n = 17) than in active GPA, healthy controls (n = 29), and inactive control diseases (n = 12). The highest NK cell percentages were found in patients with long-term remission and tapered immunosuppressive therapy. NK cell percentages >18.5 % of peripheral blood lymphocytes (n = 12/28) determined GPA inactivity with a specificity of 100 %. The differentiation into CD56dim and CD56bright NK cell subsets was unchanged in GPA (n = 28), irrespective of disease activity. Similar surface expression of the activating NK cell-receptors (NKp30, NKp46, and NKG2D) was determined. Like in healthy controls, GPA NK cells degranulated in the presence of NK cell receptor ligand bearing epithelial and lymphatic target cells.ConclusionsNK cells were not detectable in GPA granulomas. Peripheral blood NK cell percentages positively correlate with the suppression of GPA activity and could serve as a biomarker for GPA activity. Peripheral blood NK cells in GPA patients are mature NK cells with preserved immune recognition.
e24137 Background: Parenteral nutrition is used in cancer patients (pts) requiring intensive nutrition support due to insufficient dietary intake and consuming tumor disease. As there is no data of HPN in pts with migrant background (MB), this observational study examined viability of HPN, influence on QoL and nutrition status of cancer pts with and without MB. Methods: Eligibility included ECOG ≥ 1, life expectancy ≥ 4 weeks, first time HPN for at least 28 days and written informed consent. Migrant background status and patient characteristics were assessed at baseline. At day 1 (baseline), day 14 and day 28 validated questionnaires assessed QoL, nutrition status (EORTC-QLQ-C15-PAL, Subjective global assessment (SGA)), as well as feasibility and complications of HPN. Additionally, bioimpedance analysis, BMI and weight were measured to evaluate response of HPN. Results: Between Mai 2015 and November 2019, 68 pts were included, 17 of them with MB. Tumor entities were gastric (n = 41), esophageal (n = 20) and other (n = 7), treated in a curative (n = 14) or palliative (n = 54) concept. Overall, 40 pts were able to continue HPN until day 14, 26 pts until day 28. 42 pts left study due to death (1 with MB/8 overall), worsening of general condition (3/15), dietary improvement (1/2), change of supplier (1/5), informed consent withdrawal (0/1) and lost to follow up (2/11). Global QoL in all pts was stable from baseline to d14 (n = 36; 36.6 to 40.3), whereas QoL in pts with MB deteriorated (n = 9; 37.0 to 27.8). From baseline to d28, QoL in all pts improved (n = 23; 38.4 to 47.8) and in pts with MB QoL was stable (n = 7; 40.5 to 42.9). Medical problems associated with HPN occurred in 4/11 pts with MB (36%) and 11/37 pts without MB (30%), respectively. The majority of pts reported about HPN-associated organizational complications, whereas there is no significant difference of pts with MB (6/10) and without MB (20/38). SGA improvement was observed in all pts regardless of MB. During the course of HPN, there was no significant change in body weight and BMI in all pts, independent from MB. Conclusions: Overall, 59% of pts received HPN for 14 days, only 38% of pts for 28 days. Discontinuation was mainly due to disease progression. Feasibility and organizational problems did not affect duration of HPN. Assessing HPN prospectively shows, that defining the ideal point to start HPN appears to be essential for response to HPN. In our study, migrant background is not associated with a major difference in incidence of complications, viability, benefit or duration of HPN.
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