PMID- 27111223
OWN - NLM
STAT- MEDLINE
DCOM- 20170314
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 4
DP  - 2016
TI  - Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine 
      Deiminase Affect Clinical Response to Biological Disease-Modifying Antirheumatic 
      Drug in Rheumatoid Arthritis.
PG  - e0154182
LID - 10.1371/journal.pone.0154182 [doi]
LID - e0154182
AB  - OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSION: The serum IgG levels to 
      PPAD affect the clinical response to bDMARD in patients with RA.
FAU - Kobayashi, Tetsuo
AU  - Kobayashi T
AD  - General Dentistry and Clinical Education Unit, Niigata University Medical and 
      Dental Hospital, Niigata, Japan.
AD  - Division of Periodontology, Department of Oral Biological Science, Niigata 
      University Graduate School of Medical and Dental Sciences, Niigata, Japan.
FAU - Ito, Satoshi
AU  - Ito S
AD  - Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.
FAU - Kobayashi, Daisuke
AU  - Kobayashi D
AD  - Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.
AD  - Division of Clinical Nephrology and Rheumatology, Department of Homeostatic 
      Regulation Developments, Niigata University Graduate School of Medical and Dental 
      Sciences, Niigata, Japan.
FAU - Shimada, Atsushi
AU  - Shimada A
AD  - Division of Periodontology, Department of Oral Biological Science, Niigata 
      University Graduate School of Medical and Dental Sciences, Niigata, Japan.
FAU - Narita, Ichiei
AU  - Narita I
AD  - Division of Clinical Nephrology and Rheumatology, Department of Homeostatic 
      Regulation Developments, Niigata University Graduate School of Medical and Dental 
      Sciences, Niigata, Japan.
FAU - Murasawa, Akira
AU  - Murasawa A
AD  - Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.
FAU - Nakazono, Kiyoshi
AU  - Nakazono K
AD  - Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.
FAU - Yoshie, Hiromasa
AU  - Yoshie H
AD  - Division of Periodontology, Department of Oral Biological Science, Niigata 
      University Graduate School of Medical and Dental Sciences, Niigata, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160425
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Autoantibodies)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Biomarkers)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (cyclic citrullinated peptide)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.5.3.15 (Protein-Arginine Deiminases)
SB  - IM
MH  - Aged
MH  - Antibodies, Bacterial/*blood
MH  - Antirheumatic Agents/therapeutic use
MH  - Arthritis, Rheumatoid/complications/drug therapy/genetics/*immunology
MH  - Autoantibodies/blood
MH  - Bacterial Proteins/blood/*immunology
MH  - Biomarkers/blood
MH  - C-Reactive Protein/metabolism
MH  - Female
MH  - Genetic Loci
MH  - Humans
MH  - Hydrolases/blood/*immunology
MH  - Immunoglobulin G/*blood
MH  - Middle Aged
MH  - Peptides, Cyclic/antagonists & inhibitors/blood/immunology
MH  - Periodontitis/complications/drug therapy/genetics/*immunology
MH  - Polymorphism, Single Nucleotide
MH  - Porphyromonas gingivalis/*immunology
MH  - Protein-Arginine Deiminases
MH  - Retrospective Studies
MH  - Severity of Illness Index
PMC - PMC4844134
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/04/26 06:00
MHDA- 2017/03/16 06:00
PMCR- 2016/04/25
CRDT- 2016/04/26 06:00
PHST- 2016/01/21 00:00 [received]
PHST- 2016/04/11 00:00 [accepted]
PHST- 2016/04/26 06:00 [entrez]
PHST- 2016/04/26 06:00 [pubmed]
PHST- 2017/03/16 06:00 [medline]
PHST- 2016/04/25 00:00 [pmc-release]
AID - PONE-D-16-01015 [pii]
AID - 10.1371/journal.pone.0154182 [doi]
PST - epublish
SO  - PLoS One. 2016 Apr 25;11(4):e0154182. doi: 10.1371/journal.pone.0154182. 
      eCollection 2016.