Publications by authors named "Max Schuller"

2 Publications

  • Page 1 of 1

Blockade of tumor necrosis factor superfamily members CD30 and OX40 abrogates disease activity in murine immune-mediated glomerulonephritis.

Kidney Int 2021 Mar 27. Epub 2021 Mar 27.

Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. Electronic address:

Co-stimulation is a prerequisite for pathogenic activity in T cell-mediated diseases and has been demonstrated to achieve tolerance in organ-specific autoimmunity as a therapeutic target. Here, we evaluated the involvement of the tumor necrosis factor family members CD30 and OX40 in immune-complex mediated kidney disease. In vitro stimulation and proliferation studies were performed with CD4 cells from wild type and CD30/OX40 double knock-out (CD30OX40) mice. In vivo studies were performed by induction of nephrotoxic serum nephritis in wild type, CD30OX40 , CD30, OX40, reconstituted Rag1 and C57Bl/6J mice treated with αCD30L αOX40L antibodies. CD30, OX40 and their ligands were upregulated on various leukocytes in nephrotoxic serum nephritis. CD30OX40 mice, but not CD30 or OX40 mice were protected from nephrotoxic serum nephritis. Similar protection was found in Rag1 mice injected with CD4 T cells from CD30OX40 mice compared to Rag1 mice injected with CD4 T cells from wild type mice. Furthermore, CD4 T cells deficient in CD30OX40 displayed decreased expression of CCR6 in vivo. CD30OX40 cells were fully capable of differentiating into disease mediating T helper cell subsets, but showed significantly decreased levels of proliferation in vivo and in vitro compared to wild type cells. Blocking antibodies against CD30L and OX40L ameliorated nephrotoxic serum nephritis without affecting pan-effector or memory T cell populations. Thus, our results indicate disease promotion via CD30 and OX40 signaling due to facilitation of exaggerated T cell proliferation and migration of T helper 17 cells in nephrotoxic serum nephritis. Hence, co-stimulation blockade targeting the CD30 and OX40 signaling pathways may provide a novel therapeutic strategy in autoimmune kidney disease.
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http://dx.doi.org/10.1016/j.kint.2021.02.039DOI Listing
March 2021

Arylesterase Activity of HDL Associated Paraoxonase as a Potential Prognostic Marker in Patients With Sepsis and Septic Shock-A Prospective Pilot Study.

Front Med (Lausanne) 2020 22;7:579677. Epub 2020 Oct 22.

Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

High-density lipoprotein (HDL) plays an essential role in the immune system and shows effective antioxidative properties. We investigated correlations of lipid parameters with the sequential organ failure assessment (SOFA) score and the prognostic association with mortality in sepsis patients admitted to intensive care unit (ICU). We prospectively recruited consecutive adult patients with sepsis and septic shock, according to sepsis-3 criteria as well as non-sepsis ICU controls. Fifty-three patients with sepsis (49% with septic shock) and 25 ICU controls without sepsis were enrolled. Dyslipidemia (HDL-C < 40 mg/l) was more common in sepsis compared to non-sepsis patients (85 vs. 52%, = 0.002). Septic patients compared to controls had reduced HDL-C (14 vs. 39 mg/l, < 0.0001), lower arylesterase activity of the antioxidative paraoxonase of HDL (AEA) (67 vs. 111 mM/min/ml serum, < 0.0001), and a non-significant trend toward reduced cholesterol efflux capacity (9 vs. 10%, = 0.091). We observed a strong association between higher AEA and lower risk of 28-day [per 10 mM/min/ml serum increase in AEA: odds ratio (OR) = 0.76; 95% CI, 0.61-0.94; = 0.01) and ICU mortality (per 10 mM/min/ml serum increase in AEA: OR = 0.71, 95% CI, 0.56-0.90, = 0.004) in the sepsis cohort in univariable logistic regression analysis. AEA was confirmed as an independent predictor of 28-day and ICU mortality in multivariable analyses. AEA discriminated well-regarding 28-day/ICU mortality in area under the receiver operating characteristic curve (AUROC) analyses. In survival analysis, 28-day mortality estimates were 40 and 69% with AEA ≥/< the 25th percentile of AEA's distribution, respectively (log-rank = 0.0035). Both compositional and functional HDL parameters are profoundly altered during sepsis. In particular, the functionality parameter AEA shows promising prognostic potential in sepsis patients.
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http://dx.doi.org/10.3389/fmed.2020.579677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642222PMC
October 2020