Peptidylarginine deiminase, the arginine to citrulline converting enzyme, is frequently recognized by sera of patients with rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren syndrome

Scand J Rheumatol. 2003;32(6):337-42. doi: 10.1080/03009740410004990.


Objective: Antibodies to citrulline-containing epitopes of filaggrin are highly specific for rheumatoid arthritis (RA). We studied whether the enzyme peptidylarginine deiminase (PAD), responsible for the post-translational modification of peptide-bound arginine residues to citrulline, constitutes an antigen for patients with RA.

Methods: IgG antibodies to PAD were measured by enzyme-linked immunosorbent assay (ELISA) in sera from patients with RA, systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), multiple sclerosis (MS) and healthy controls.

Results: Compared to healthy controls, raised levels of IgG antibodies to PAD were found in 50 of 57 recent-onset RA patients (88%) and in 40 (70%) of the same 57 patients 3 years later (p<0.0001 for both comparisons). Eleven of 51 (22%) patients with RA of long duration, 19/43 (44%) patients with SLE and 16/19 (84%) patients with pSS, but none of 20 patients with MS, had elevated anti-PAD levels.

Conclusion: The arginine-citrulline converting enzyme PAD was recognized as a new antigen against which patients with inflammatory rheumatic diseases frequently show IgG class antibodies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Antinuclear / immunology
  • Arthritis, Rheumatoid / enzymology*
  • Arthritis, Rheumatoid / immunology
  • Biomarkers / analysis
  • Citrulline / analysis
  • Citrulline / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Filaggrin Proteins
  • Humans
  • Hydrolases / analysis
  • Hydrolases / metabolism*
  • Intermediate Filament Proteins / analysis
  • Intermediate Filament Proteins / metabolism*
  • Lupus Erythematosus, Systemic / enzymology*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Middle Aged
  • Probability
  • Prognosis
  • Protein-Arginine Deiminases
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Sjogren's Syndrome / enzymology*
  • Sjogren's Syndrome / immunology


  • Antibodies, Antinuclear
  • Biomarkers
  • FLG protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Citrulline
  • Hydrolases
  • Protein-Arginine Deiminases