Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes.

TLDR

Systemic lupus erythematosus is a multisystem autoimmune disease in which autoantibodies target a diverse array of autoantigens across subcellular compartments. Oxidative modification at the ER and nuclear membrane interfaces may serve as a unifying mechanism that renders these molecules immunogenic. The study shows that on apoptotic keratinocyte surfaces, autoantigens cluster into two bleb populations: small blebs enriched in fragmented ER, ribosomes, and Ro, and larger apoptotic bodies containing nucleosomal DNA, Ro, La, and snRNPs, all positioned near ER and nuclear membranes where reactive oxygen species are generated.

Abstract

Systemic lupus erythematosus is a multisystem autoimmune disease in which the autoantibody response targets a variety of autoantigens of diverse subcellular location. We show here that these autoantigens are clustered in two distinct populations of blebs at the surface of apoptotic cells. The population of smaller blebs contains fragmented endoplasmic reticulum (ER) and ribosomes, as well as the ribonucleoprotein, Ro. The larger blebs (apoptotic bodies) contain nucleosomal DNA, Ro, La, and the small nuclear ribonucleoproteins. These autoantigen clusters have in common their proximity to the ER and nuclear membranes, sites of increased generation of reactive oxygen species in apoptotic cells. Oxidative modification at these sites may be a mechanism that unites this diverse group of molecules together as autoantigens.