Autoimmunity to peptidyl arginine deiminase type 4 precedes clinical onset of rheumatoid arthritis

Wiley - Tập 62 Số 9 - Trang 2633-2639 - 2010
Jason R. Kolfenbach1, Kevin D. Deane2, Lezlie A. Derber2, Colin O’Donnell3, William R. Gilliland4, Jess D. Edison4, Antony Rosen5, Erika Darrah5, Jill M. Norris3, V. Michael Holers2
1Univ. of Colorado Denver, Aurora, 80045, USA.
2University of Colorado Denver, Aurora#TAB#
3Colorado School of Public Health and University of Colorado Denver, Aurora
4Walter Reed Army Medical Center, Washington, DC
5Johns Hopkins University School of Medicine, Baltimore, Maryland

Tóm tắt

AbstractObjectiveTo determine whether antibodies against peptidyl arginine deiminase type 4 (PAD‐4) are present in the preclinical phase of rheumatoid arthritis (RA) and to compare the timing and extent of their appearance with those of other preclinical autoantibodies.MethodsPrediagnosis serum samples from 83 patients with RA were evaluated for the presence of anti–PAD‐4 antibody, anti–cyclic citrullinated peptide (anti‐CCP) antibody, and rheumatoid factor. In addition, a control cohort (n = 83) matched by age, sex, race, number of serum samples, and duration of serum storage was tested for the presence of anti–PAD‐4 antibody to determine its sensitivity and specificity for the subsequent development of RA.ResultsFifteen of 83 patients with RA (18.1%) had at least 1 prediagnosis sample positive for anti–PAD‐4. One of 83 control subjects (1.2%) had at least 1 positive sample, resulting in a sensitivity and specificity of 18.1% and 98.8%, respectively, of anti–PAD‐4 for the future development of RA. The mean duration of anti–PAD‐4 positivity prior to clinical diagnosis was 4.67 years. Anti–PAD‐4 positivity was associated with anti‐CCP positivity (odds ratio 5.13 [95% confidence interval 1.07–24.5]). In subjects with prediagnosis samples that were positive for both antibodies, anti‐CCP positivity predated anti–PAD‐4 positivity in 9 of 13 cases (69%).ConclusionAutoantibodies to PAD‐4 are present during the preclinical phase of RA in a subset of patients and are associated with anti‐CCP positivity. Further exploration is needed regarding the timing of appearance and disease‐related effects of PAD‐4 autoimmunity.

Từ khóa


Tài liệu tham khảo

10.1002/art.11223

10.1136/ard.2005.040659

10.1002/art.20018

10.1136/ard.2007.076679

Aho K, 1991, Rheumatoid factors antedating clinical rheumatoid arthritis, J Rheumatol, 18, 1282

10.1002/art.23596

10.1038/ng1206

10.1002/art.21309

10.1093/rheumatology/kel023

10.1086/498651

10.1093/rheumatology/kei008

10.1136/ard.2009.111294

10.1080/03009740410004990

10.1080/03009740510026346-1

10.1136/ard.2007.080267

Zhao J, 2008, Prevalence and significance of anti‐peptidylarginine deiminase 4 antibodies in rheumatoid arthritis, J Rheumatol, 35, 969

10.1002/art.1780310302

10.1002/1529-0131(200102)44:2<389::AID-ANR58>3.0.CO;2-R

10.1007/b97377

10.1093/biostatistics/1.4.355

10.1186/ar1187

10.1002/art.20044

10.1002/art.27230

10.1136/ard.2008.094490

10.1002/art.27439

10.1196/annals.1422.034

10.1002/art.20659

Cuchacovich M, 2008, Basal anti‐cyclic citrullinated peptide (anti‐CCP) antibody levels and a decrease in anti‐CCP titres are associated with clinical response to adalimumab in rheumatoid arthritis, Clin Exp Rheumatol, 26, 1067

Roth EB, 2006, Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumatoid arthritis—new pathways to epitope spreading, Clin Exp Rheumatol, 24, 12

10.1136/ard.2007.071662

10.1016/S0140-6736(02)08213-2

10.1136/ard.2005.049338

Thông tin
Thông tin xuất bản

Wiley

Tập 62 Số 9

2633-2639

Thông tin tác giả