Deficient ferritin immunoreactivity in tissues from niemann-pick type C patients: extension of findings to fetal tissues, H and L ferritin isoforms, but also one case of the rare Niemann-Pick C2 complementation group

Abstract

Previous studies employing rabbit polyclonal anti-human liver ferritin have shown an absence of L ferritin immunoreactivity in liver and spleen tissue from patients with Niemann-Pick disease type C1 (NPC1). The great majority of NPC cases is caused by defects of the NPC1 gene, and a minority by those of another (NPC2). In this study using polyclonal and monoclonal antibodies we show the deficiency of H and L ferritin isoforms in various NPC tissues, including fetal NPC1, not previously described. In particular, evidence is provided for deficiency in H and L ferritins in tissues, except lung, from a patient with Niemann-Pick disease type C2 (NPC2). The present findings indicate that H and L ferritins are deficient in both NPC types characterized by accumulation of unesterified cholesterol and additional metabolites in the endosomal/lysosomal system. We hypothesize that the lesions in NPC1 and NPC2 block the intracellular utilization not only of cholesterol, but also that of iron for the synthesis of cytosolic ferritin.