Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine Deiminase Affect Clinical Response to Biological Disease-Modifying Antirheumatic Drug in Rheumatoid Arthritis.
To determine whether serum immunity to Porphyromonas gingivalis peptidylarginine deiminase (PPAD) affects the clinical response to biological disease-modifying antirheumatic drug (bDMARD) in patients with rheumatoid arthritis (RA).



In a retrospective study, rheumatologic and periodontal conditions of 60 patients with RA who had been treated with conventional synthetic DMARD were evaluated before (baseline) and after 3 and 6 months of bDMARD therapy. After serum levels of anti-PPAD immunoglobulin G (IgG) were determined at baseline, the patients were respectively divided into two groups for high and low anti-PPAD IgG titers according to the median measurements. Genotypes at 8 functional single nucleotide polymorphisms (SNPs) related to RA were also determined.



After 3 and 6 months of therapy, patients with low anti-PPAD IgG titers showed a significantly greater decrease in changes in the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP) (P = 0.04 for both) and anti-cyclic citrullinated peptide (CCP) IgG levels (P = 0.03 and P = 0.04) than patients with high anti-PPAD IgG titers, although these parameter values were comparable at baseline. The anti-PPAD IgG titers were significantly positively correlated with changes in the DAS28-CRP (P = 0.01 for both) and the anti-CCP IgG levels (P = 0.02 for both) from baseline to 3 and 6 months later. A multiple regression analysis revealed a significantly positive association between the anti-PPAD IgG titers and changes in the DAS28-CRP after 6 months of bDMARD therapy (P = 0.006), after adjusting for age, gender, smoking, periodontal condition, and RA-related SNPs.



The serum IgG levels to PPAD affect the clinical response to bDMARD in patients with RA.
General Dentistry and Clinical Education Unit, Niigata University Medical and Dental Hospital, Niigata, Japan.|Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Tetsuo
T
Kobayashi
Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.
Satoshi
S
Ito
Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.|Division of Clinical Nephrology and Rheumatology, Department of Homeostatic Regulation Developments, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Daisuke
D
Kobayashi
Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Atsushi
A
Shimada
Division of Clinical Nephrology and Rheumatology, Department of Homeostatic Regulation Developments, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Ichiei
I
Narita
Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.
Akira
A
Murasawa
Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.
Kiyoshi
K
Nakazono
Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Hiromasa
H
Yoshie
D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D001426:Bacterial Proteins / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D056426:Genetic Loci; D006801:Humans; D006867:Hydrolases / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology; D010518:Periodontitis / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D016966:Porphyromonas gingivalis / Q000276:immunology*; D000076342:Protein-Arginine Deiminases; D012189:Retrospective Studies; D012720:Severity of Illness Index
D000907:Antibodies, Bacterial; D018501:Antirheumatic Agents; D001323:Autoantibodies; D001426:Bacterial Proteins; D015415:Biomarkers; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002097:C-Reactive Protein; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases