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.
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.


CONCLUSIONS
The arginine-citrulline converting enzyme PAD was recognized as a new antigen against which patients with inflammatory rheumatic diseases frequently show IgG class antibodies.
Nissinen
R
R
National Public Health Institute, Department of Molecular Medicine, Biomedicum, Helsinki, Finland. riikka.nissinen@ktl.fi
Paimela
L
L
Julkunen
H
H
Tienari
P J
PJ
Leirisalo-Repo
M
M
Palosuo
T
T
Vaarala
O
O
D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D002956:Citrulline / Q000032:analysis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D006867:Hydrolases / Q000032:analysis / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D000076342:Protein-Arginine Deiminases; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000201:enzymology* / Q000276:immunology
D000974:Antibodies, Antinuclear; D015415:Biomarkers; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D002956:Citrulline; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases