PARP1 as a novel therapeutic and diagnostic tool in autoimmune rheumatic diseases: a systematic literature review

ADP-ribosylation is a reversible post-translational modification regulated by poly(ADP-ribose) polymerases (PARPs), a family of enzymes involved in DNA repair, transcriptional regulation, and immune responses. Among the 17 known PARP family members, PARP1 is the most extensively studied in autoimmune rheumatic diseases (ARDs). Although increasing evidence implicates PARP1 in ARD pathogenesis, its potential diagnostic and therapeutic relevance has not been systematically synthesised. This systematic literature review (SLR) aimed to evaluate the role of PARP1 in the pathogenesis, diagnosis and treatment of ARDs. MEDLINE and Embase databases were searched on 6th May 2026 using MeSH keywords for systemic ARDs, PARP1 and PARP inhibitors. Studies involving adult ARD patients and relevant animal models were included. Of 3564 records identified (post-deduplication), 41 studies were included. Seventeen studies included human ARD cohorts and nine used murine models recapitulating specific ARDs. Most studies focused on systemic lupus erythematosus (SLE; n = 18), rheumatoid arthritis (n = 14), and systemic sclerosis (SSc; n = 7). Across experimental models, inhibition or genetic disruption of PARP1 frequently attenuated inflammatory responses, reducing pro-inflammatory mediator expression, oxidative stress, and tissue damage. However, PARP1 also demonstrated context-dependent regulatory effects in immune signalling pathways. In SLE and SSc, reduced PARP1 activity and impaired DNA repair capacity were reported. Genetic association studies produced heterogeneous findings, while several studies identified PARP1-related autoantibodies or activity changes as potential diagnostic biomarkers, particularly in SLE. Overall, our SLR highlights PARP1 as an important regulator of immune pathways in ARDs, with potential relevance for future diagnostic and therapeutic strategies. PROSPERO: CRD420251000954.