title: The Sjogren's syndrome-associated autoantigen Ro52 is an E3 ligase that regulates proliferation and cell death.
abstract: Patients affected by Sjögren's syndrome and systemic lupus erythematosus (SLE) carry autoantibodies to an intracellular protein denoted Ro52. Although the serologic presence of Ro52 autoantibodies is used clinically for diagnostic purposes, the function of the protein or why it is targeted as an autoantigen in several rheumatic conditions has not been elucidated. In this study, we show that the expression of Ro52 is significantly increased in PBMC of patients with Sjögren's syndrome and SLE, and demonstrate that Ro52 is a RING-dependent E3 ligase involved in ubiquitination. Overexpression of Ro52, but not of Ro52 lacking the RING domain, in a mouse B cell line lead to decreased growth in steady state and increased cell death after activation via the CD40 pathway. The role of Ro52 in activation-mediated cell death was further confirmed as a reduction in Ro52 expression restored cell viability. These findings suggest that the increased expression of the Ro52 autoantigen in patients may be directly involved in the reduced cellular proliferation and increased apoptotic cell death observed in Sjögren's syndrome and SLE, and may thus contribute to the autoantigenic load and induction of autoimmune B and T cell responses observed in rheumatic patients.
authors: Rheumatology Unit, Department of Medicine, Karolinska Institutet at Danderyd Hospital, Karolinska Institutet, S-17176 Stockholm, Sweden.
authors: Alexander
authors: A
authors: Espinosa
authors: Wei
authors: W
authors: Zhou
authors: Monica
authors: M
authors: Ek
authors: Malin
authors: M
authors: Hedlund
authors: Susanna
authors: S
authors: Brauner
authors: Karin
authors: K
authors: Popovic
authors: Linn
authors: L
authors: Horvath
authors: Therese
authors: T
authors: Wallerskog
authors: Mohamed
authors: M
authors: Oukka
authors: Filippa
authors: F
authors: Nyberg
authors: Vijay K
authors: VK
authors: Kuchroo
authors: Marie
authors: M
authors: Wahren-Herlenius