Autoantibodies to the nuclear envelope: Functional anatomy of the HEp-2 cell substrate

The nuclear envelope (NE) is a complex intracellular structure unique to eukaryotic cells. The principal components identified by a variety of methods include the inner nuclear lamina comprised primarily of lamin proteins, the inner nuclear membrane (INM), the nuclear pore (NuP) complexes comprised of NuP proteins and the outer nuclear membrane (ONM). Dating to the earliest studies, the specific NE targets of human autoantibodies included: lamins A, B and C of the nuclear lamina, emerin, lamin B receptor (LBR), lamina-associated polypeptide 1 (LAP1) and lamina-associated polypeptide 2 (LAP2) of the INM and gp210/p210 and Translocated promoter region (Tpr) of the NuP. While autoantibodies to NE components are reported in a wide variety of diseases, their clinical use and importance have become paramount in autoimmune liver diseases, particularly primary biliary cholangitis. This review provides an overview of these findings and presents an atlas of the nuclear envelope components and molecular autoantibody targets and their intra-NE distribution that is used to interpret routine anti-cellular antibody testing using HEp-2 substrates.