Session Title: Rheumamtoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
Background/Purpose: Antibodies directed against peptidylarginine deiminase type 4 (PAD-4) are present in a subset of patients with rheumatoid arthritis (RA) and are associated with more severe joint destruction. These autoantibodies have been detected preceding the clinical diagnosis of RA in some patients. The objective of this study is to determine whether anti-PAD-4 antibodies are present in first-degree relatives of RA patients in two indigenous North American (INA) populations with high prevalence of RA.
Methods: Participants were recruited from two INA populations. We included RA patients (probands), their unaffected first-degree relatives (FDRs), and healthy controls, including both INA and Caucasian controls. Participants were interviewed for the presence of joint symptoms and underwent a joint examination by a rheumatologist. Sera were tested for the presence of anti-PAD-4 antibodies, anti-cyclic citrullinated peptide (CCP) antibodies, and rheumatoid factor (RF) IgM by ELISA. HLA-DRB1 subtyping was performed and participants were classified according to the presence or absence of shared epitope alleles.
Results: Antibodies to PAD-4 were detected in 27 of 82 (32.9%) RA probands; 2 of 147 (1.4%) FDRs; and 0 of 64 controls, including 20 Caucasian and 44 INA controls (p <0.0001). Anti-CCP antibodies were present in 26/27 (96.3%) of probands with anti-PAD-4, as compared to 42/54 (77.8%) of probands without anti-PAD-4 (p=0.05). In the FDRs, anti-CCP was present in 39/144 (27.1%) and there was no overlap between positivity for anti-CCP and PAD-4. None of the controls had anti-CCP antibodies detected. CCP and RF were both positive in 80.8% of the probands, but the association between RF and PAD-4 positivity was not statistically significant (p=0.14). One or more copy of an HLA-DRB1 shared epitope allele was present in 92% of probands and 82% of relatives (p=0.13), and there was no association between the presence of a shared epitope allele and PAD-4 positivity in probands (p=0.65) or relatives (p=1.0).
Conclusion: Despite a significant prevalence of anti-CCP in FDRs of INA RA patients, anti-PAD-4 antibodies were almost exclusively found in existing RA, suggesting these autoantibodies may be highly specific for RA. The prevalence of anti-PAD-4 antibodies in INA people with RA is similar to the prevalence described in other populations and these autoantibodies are strongly associated with anti-CCP in RA.
E. D. Ferucci,
T. L. Choromanski,
D. B. Robinson,
M. M. Newkirk,
M. J. Fritzler,
Inova Diagnostics, Inc.,
H. S. El-Gabalawy,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prevalence-of-anti-peptidylarginine-deiminase-type-4-antibodies-in-rheumatoid-arthritis-and-unaffected-first-degree-relatives-in-indigenous-north-american-populations/