Contribution of anti-CCP antibodies, proximal interphalangeal joint involvement, HLA-DRB1 shared epitope, and PADI4 as risk factors for the development of rheumatoid arthritis in palindromic rheumatism.
OBJECTIVE
To determine which variables at baseline are predictive for the development of rheumatoid arthritis (RA) from palindromic rheumatism (PR) in a Japanese population.


METHODS
Anti-cyclic citrullinated peptide (anti-CCP) antibodies, joint involvement pattern, genotypes of HLA-DRB1, peptidylarginine deiminase (PADI4), and protein tyrosine phosphatase (PTPN22) were examined in 28 patients with PR at baseline, and their clinical outcome was prospectively evaluated. The same variables were also investigated in 38 healthy controls.


RESULTS
Eleven out of 28 patients with PR developed RA. The prevalence of anti-CCP antibodies in the PR patients who developed RA was significantly higher compared to the patients who did not. Proximal interphalangeal (PIP) joint involvement at baseline was also predictive towards the development of RA. Compared with the controls, differences in the frequency of single-nucleotide polymorphism (SNP) on padi4_104 [T(RA susceptible)-->C(RA non-susceptible)] and the presence of an RA susceptible homozygote of the PADI4 haplotype were detected in patients with PR whereas we could not find any further difference in PR patients who developed RA compared to PR patients who do not develop RA in PADI4. None of the subjects possessed the PTPN22 SNP (1858C-->T). Cox regression analysis revealed that anti-CCP antibodies as well as PIP involvement are the most relevant variables for the development of RA from PR. None of the PR patients with either HLA-DRB1*SE alleles (or the HLA-DRB1*0405 allele) or anti-CCP antibodies developed RA.


CONCLUSIONS
Anti-CCP antibodies, in relation to HLA-DRB1*SE carriership, and PIP involvement are predictive for the development of RA from PR in the Japanese population.
Tamai
M
M
Unit of Translational Medicine, Department of Immunology and Rheumatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Kawakami
A
A
Iwamoto
N
N
Arima
K
K
Aoyagi
K
K
Eguchi
K
K
D000483:Alleles; D001323:Autoantibodies / Q000276:immunology; D018450:Disease Progression; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005384:Finger Joint / Q000276:immunology*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D006867:Hydrolases / Q000235:genetics* / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D012044:Regression Analysis; D012216:Rheumatic Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D018709:Statistics, Nonparametric
D001323:Autoantibodies; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases