ABSTRACT
Pure red cell aplasia (PRCA) is characterised by normocytic normochromic anaemia, reticulocytopenia and reduced erythroid precursors in bone marrow. PRCA as an immune-related adverse event secondary to immune checkpoint inhibitor (ICI) therapy is rare. Steroids are usually used first line to treat ICI-induced PRCA. Here, we report a case of ICI-induced PRCA with no response to steroids but where intravenous (IV) immunoglobulin was successfully used second line. ICI therapy was reinitiated following PRCA resolution. PRCA recurrence did not occur.
ABSTRACT
Liver X receptor-α (LXRα) regulates cellular cholesterol abundance and potently activates hepatic lipogenesis. Here we show that at least 1 in 450 people in the UK Biobank carry functionally impaired mutations in LXRα, which is associated with biochemical evidence of hepatic dysfunction. On a western diet, male and female mice homozygous for a dominant negative mutation in LXRα have elevated liver cholesterol, diffuse cholesterol crystal accumulation and develop severe hepatitis and fibrosis, despite reduced liver triglyceride and no steatosis. This phenotype does not occur on low-cholesterol diets and can be prevented by hepatocyte-specific overexpression of LXRα. LXRα knockout mice exhibit a milder phenotype with regional variation in cholesterol crystal deposition and inflammation inversely correlating with steatosis. In summary, LXRα is necessary for the maintenance of hepatocyte health, likely due to regulation of cellular cholesterol content. The inverse association between steatosis and both inflammation and cholesterol crystallization may represent a protective action of hepatic lipogenesis in the context of excess hepatic cholesterol.