Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects.
Emmungil. Hakan H; İlgen. Ufuk U; Direskeneli. Rafi Haner RH
Key Findings
- PsA patients often have autoantibodies targeting LL-37, indicating an autoimmune component.
- Genetic risk for PsA is linked to MHC class I and several non‑HLA genes (IL12B, IL23R, TYK2, etc.).
- Immune infiltrates in joints show CD8+ T‑cell clones, reduced regulatory T‑cell function, and respond to calcineurin/mTOR inhibition.
Practical Outcomes
- For biohackers, the presence of anti‑LL‑37 antibodies suggests a potential biomarker for autoimmune activity in skin/joint disease. Targeting the mTOR pathway (e.g., with rapamycin or related compounds) may be a therapeutic angle, though clinical evidence is still limited. Monitoring inflammation and immune status remains key before trying any off‑label interventions.
Summary
The study shows that psoriatic arthritis (PsA) is driven in part by the immune system attacking the body, including making antibodies against a protein called LL-37. Genetic factors and immune cell changes also play a role, and drugs that block calcineurin/mTOR pathways seem to help.
Abstract
Psoriatic arthritis (PsA) is an underdiagnosed entity with a broad impact on the quality of life. Although the pathogenesis is largely unknown, autoimmune footprints of the inflammation in PsA have increasingly been recognized. Most of the genetic variation predisposing to PsA is mapped to the class I major histocompatibility complex (MHC) region and shared by a variety of autoimmune diseases. Polymorphisms in the genes IL12B, IL23R, IL13, TNIP1, TRAF3IP2, TYK2, and many others explain the non- HLA genetic risk with little known functional consequences. Entheseal and synovial cellular infiltrate with oligoclonal CD8+ T cells and occasional germinal centers, loss of regulatory T cell function, and specific autoantibodies such as anti-PsA peptide, anti-LL-37, and anti-ADAMTSL5 are the immunopathological findings suggestive of autoimmunity. These were supported by clinical observations of autoimmune multimorbidity and treatment response to calcineurin/mTOR and co-stimulation inhibition.
Study Information
pubmed
2021
2021-08-30T00:00:00.000Z
10.3906/sag-2011-235
15
130