Chinese Study Links High Autoantibody Levels Against PD-1 to Lupus Disease Activity

Chinese Study Links High Autoantibody Levels Against PD-1 to Lupus Disease Activity

Patients with new-onset lupus erythematosus (SLE) have high levels of autoantibodies against programmed cell death protein 1 (PD-1), an immune response co-inhibitor, new research from China shows.

The study, “Elevated serum autoantibodies against co-inhibitory PD-1 facilitate T cell proliferation and correlate with disease activity in new-onset systemic lupus erythematosus patients,” appeared in the journal Arthritis Research and Therapy.

Although the precise mechanisms triggering SLE-related pathology remain unknown, available evidence suggests that, once immune tolerance is compromised, T-cells are the primary contributors to appearance of the disease and its progression.

PD-1 plays an inhibitory role in immune response after T-cell activation, thereby maintaining the balance of immune tolerance. Studies in mouse models showed that PD-1 deficiency plays a key role in the pathogenesis of autoimmune diseases.

Researchers led by Chengde Yan of the Shanghai Jio Tong University School of Medicine found lower levels of PD-1 in the T-cells of SLE patients. They also discovered that such patients had more neutrophils (white blood cells that play a key role in innate immune responses) containing PD-1 ligand — which triggers SLE activity and severity. This evidence suggests a critical role of PD-1 in SLE. However, the serum profile of autoantibodies against PD-1 in SLE remains to be determined.

The team detected serum levels of anti-PD-1 autoantibodies in 90 untreated new-onset SLE patients, 50 with rheumatoid arthritis, 50 with primary Sjogren’s syndrome, 25 with ankylosing spondylitis — a type of spinal arthritis — and 80 healthy controls. Scientists also  analyzed the correlation of anti-PD-1 autoantibodies with clinical manifestations and laboratory parameters related to new-onset SLE, and measured the effect of purified anti-PD-1 autoantibodies from SLE patients on T-cell proliferation in vitro.

The results showed increased levels of anti-PD-1 IgG (the most common type of antibody), especially in new-onset SLE patients with typical symptoms of the disease, including malar rash, arthritis, serositis  and hematological, renal and neurological involvement. Importantly, serum levels of anti-PD-1 IgG were linked with SLE disease activity.

Furthermore, purified anti-PD-1 IgG collected from SLE patients facilitated T-cell proliferation in the presence of dendritic cells, which are antigen-presenting cells of the immune system.

“The current study indicates, for the first time, that the serum levels of co-inhibitor autoantibodies against PD-1 are elevated in new-onset SLE patients and are associated with disease activity in SLE,” the team concluded. “Autoantibodies against PD-1, facilitating T cell proliferation, revealed a new insight into the function of negative regulation signals involved in the pathogenesis of SLE.”

José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
follow me
×
José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
follow me
Latest Posts
  • pregnancy
  • Neovacs vaccine trial results
  • osteopontin
  • rubella, juvenile SLE

Leave a Comment

Your email address will not be published. Required fields are marked *