Lupus nephritis, a well-known complication in systemic lupus erythematosus, is characterised by a... more Lupus nephritis, a well-known complication in systemic lupus erythematosus, is characterised by a proliferative glomerulonephritis or membranous nephropathy along with a full-house immunofluorescence pattern on renal biopsy. There are very few exceptions in which similar histopathological findings are present, but case reports show that an increasing number of HIV-positive patients (mostly black Africans, but also white patients) have HIV-immune complex disease (HIVICK), which can mimic lupus nephritis. Lupus-like HIVICK is treated differently than 'true' lupus nephritis, so distinction is warranted.
ABSTRACT Background & aims Ulcerative colitis is characterized by severe damage of the co... more ABSTRACT Background & aims Ulcerative colitis is characterized by severe damage of the colon epithelium. Wnt-signaling is important for repair and regeneration of the intestinal epithelium. Lithium activates Wnt-signaling through inhibition of Glycogen Synthase Kinase 3β. Lithium induced prolonged remission in a patient with a bipolar disorder and ulcerative colitis, suggesting a therapeutic potential for ulcerative colitis. Methods Here, we investigated the effect of lithium (4 mg/day via a subcutaneous osmotic pump) on 5% dextran sulfate sodium-induced colitis in female Balb/c mice. Results At day 7, colon length was significantly increased in lithium-treated compared to untreated mice (8.6 cm [7.0–9.5] versus 7.6 cm [6.7–8.0], p < 0.05). As expected, dextran sulfate sodium treatment reduced colon length (5.9 cm [5.1–6.5], p < 0.001), but this was not altered by lithium (6.0 cm [5.5–7.0]). No significant differences were detected in bodyweight, histology, inflammatory (myeloperoxidase, iNOS, cytokines) and Wnt-pathway (β-catenin, p-Glycogen Synthase Kinase 3β) markers between dextran sulfate sodium- and lithium/dextran sulfate sodium-treated mice. Conclusions Lithium has no therapeutic effect on dextran sulfate sodium-induced colitis in mice. However, in the healthy intestine it shows intestinothrophic potential that might be beneficial for short bowel patients.
It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor cl... more It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones. Combined single-cell RNA sequencing, flow cytometry, and immunohistochemistry studies of the innate immune compartment in the bone marrow of patients with acute myeloid leukemia (AML) reveal a shift toward a tumor-supportive M2-polarized macrophage landscape with an altered transcriptional program, with enhanced fatty acid oxidation and NAD + generation. Functionally, these AML-associated macrophages display decreased phagocytic activity and intra–bone marrow coinjection of M2 macrophages together with leukemic blasts strongly enhances in vivo transformation potential. A 2-day in vitro exposure to M2 macrophages results in the accumulation of CALR low leukemic blast cells, which are now protected against phagocytosis. Moreover, M2-exposed “trained” leukemic blasts display increased mitochondrial metabolism, in part mediated via mitochondrial transfer. Our study provides insight into the mechanisms by which the immune landscape contributes to aggressive leukemia development and provides alternatives for targeting strategies aimed at the tumor microenvironment.
Lupus nephritis, a well-known complication in systemic lupus erythematosus, is characterised by a... more Lupus nephritis, a well-known complication in systemic lupus erythematosus, is characterised by a proliferative glomerulonephritis or membranous nephropathy along with a full-house immunofluorescence pattern on renal biopsy. There are very few exceptions in which similar histopathological findings are present, but case reports show that an increasing number of HIV-positive patients (mostly black Africans, but also white patients) have HIV-immune complex disease (HIVICK), which can mimic lupus nephritis. Lupus-like HIVICK is treated differently than 'true' lupus nephritis, so distinction is warranted.
ABSTRACT Background & aims Ulcerative colitis is characterized by severe damage of the co... more ABSTRACT Background & aims Ulcerative colitis is characterized by severe damage of the colon epithelium. Wnt-signaling is important for repair and regeneration of the intestinal epithelium. Lithium activates Wnt-signaling through inhibition of Glycogen Synthase Kinase 3β. Lithium induced prolonged remission in a patient with a bipolar disorder and ulcerative colitis, suggesting a therapeutic potential for ulcerative colitis. Methods Here, we investigated the effect of lithium (4 mg/day via a subcutaneous osmotic pump) on 5% dextran sulfate sodium-induced colitis in female Balb/c mice. Results At day 7, colon length was significantly increased in lithium-treated compared to untreated mice (8.6 cm [7.0–9.5] versus 7.6 cm [6.7–8.0], p < 0.05). As expected, dextran sulfate sodium treatment reduced colon length (5.9 cm [5.1–6.5], p < 0.001), but this was not altered by lithium (6.0 cm [5.5–7.0]). No significant differences were detected in bodyweight, histology, inflammatory (myeloperoxidase, iNOS, cytokines) and Wnt-pathway (β-catenin, p-Glycogen Synthase Kinase 3β) markers between dextran sulfate sodium- and lithium/dextran sulfate sodium-treated mice. Conclusions Lithium has no therapeutic effect on dextran sulfate sodium-induced colitis in mice. However, in the healthy intestine it shows intestinothrophic potential that might be beneficial for short bowel patients.
It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor cl... more It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones. Combined single-cell RNA sequencing, flow cytometry, and immunohistochemistry studies of the innate immune compartment in the bone marrow of patients with acute myeloid leukemia (AML) reveal a shift toward a tumor-supportive M2-polarized macrophage landscape with an altered transcriptional program, with enhanced fatty acid oxidation and NAD + generation. Functionally, these AML-associated macrophages display decreased phagocytic activity and intra–bone marrow coinjection of M2 macrophages together with leukemic blasts strongly enhances in vivo transformation potential. A 2-day in vitro exposure to M2 macrophages results in the accumulation of CALR low leukemic blast cells, which are now protected against phagocytosis. Moreover, M2-exposed “trained” leukemic blasts display increased mitochondrial metabolism, in part mediated via mitochondrial transfer. Our study provides insight into the mechanisms by which the immune landscape contributes to aggressive leukemia development and provides alternatives for targeting strategies aimed at the tumor microenvironment.
Uploads
Papers by Arjan Diepstra