A systematic review of genetic associations, autoantibody profiles, and research gaps of peptidyl arginine deiminases type 2 (PAD2) and PAD4 in rheumatoid arthritis.
Abang Ulrich Akwo, Ketonze Valademy Ketu, Oumar Mahamat
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In 30 seconds
This systematic review with narrative synthesis examined genetic associations involving PADI2 and PADI4 and anti-PAD2/anti-PAD4 autoantibodies in rheumatoid arthritis (RA). It included 42 genetic studies and 18 autoantibody studies. PADI4 polymorphisms were associated with RA in Asian populations (pooled odds ratio 1.23, 95% confidence interval 1.16-1.31), while findings in Europeans were equivocal. Anti-PAD4 antibodies were reported in 18-35% and correlated with severe erosive disease; anti-PAD2 antibodies had an approximately 18.5% prevalence and correlated with milder disease. No studies in African populations were identified.
Key findings
- PADI4 polymorphisms were associated with RA in Asian populations (pooled odds ratio 1.23, 95% confidence interval 1.16-1.31); European findings were equivocal.
- The PADI2 variation rs1005753 was protective in Southeast Asians (OR = 0.87 (95% CI =0.77-0.99)).
- Anti-PAD4 antibodies had 18-35% prevalence and correlated with severe erosive disease; anti-PAD2 antibodies had ∼18.5% prevalence and correlated with milder disease.
- No studies of PADI2/PADI4 genetics or anti-PAD antibody profiles in African populations were found.
Why it matters
The review brings together evidence that PAD-related genetic variants and autoantibodies may differ in their associations with RA susceptibility and disease severity across populations. The absence of African-population studies limits understanding of how representative these findings are and highlights an evidence gap relevant to equitable evaluation of biomarkers and therapeutic strategies.
What to keep in mind
The review found no relevant studies in African populations, and genetic associations varied by population, with equivocal findings among Europeans.