Abstract | OBJECTIVE: The location and mechanisms involved in the initial generation of autoantibodies to citrullinated and noncitrullinated proteins/ peptides during the natural history of rheumatoid arthritis (RA) development is incompletely understood. This study sought to explore individual antibody responses to citrullinated and noncitrullinated proteins/ peptides in the sputum and associations with neutrophil extracellular traps (NETs) in subjects at risk for the future development of RA. METHODS: Serum and sputum samples were obtained from 41 RA-free subjects who were considered at risk for the development of RA based on familial or serologic risk factors, from 20 subjects classified as having RA, and from 22 healthy control subjects. Samples were evaluated using a bead-based array for IgG reactivity to 29 citrullinated proteins/ peptides and 21 noncitrullinated proteins/ peptides. Cutoff levels for antibody positivity were established in a separate control group. NET levels in the sputum were measured using sandwich enzyme-linked immunosorbent assays that quantitate DNA- myeloperoxidase and DNA- neutrophil elastase complexes. RESULTS: CONCLUSION: These findings suggest that sputum antibody reactivity to particular citrullinated and noncitrullinated proteins/ peptides is specific for RA and for subjects at risk of RA, and the association of these proteins/ peptides with NETs may be a key feature of early RA-related autoimmunity in the lung. These results further support the hypothesis that the lung plays a role in early RA-related autoimmunity.
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Authors | M Kristen Demoruelle, Emily Bowers, Lauren J Lahey, Jeremy Sokolove, Monica Purmalek, Nickie L Seto, Michael H Weisman, Jill M Norris, Mariana J Kaplan, V Michael Holers, William H Robinson, Kevin D Deane |
Journal | Arthritis & rheumatology (Hoboken, N.J.)
(Arthritis Rheumatol)
Vol. 70
Issue 4
Pg. 516-527
(04 2018)
ISSN: 2326-5205 [Electronic] United States |
PMID | 29266801
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2017, American College of Rheumatology. |
Chemical References |
- Autoantibodies
- Autoantigens
- Peptides, Cyclic
- cyclic citrullinated peptide
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Topics |
- Adult
- Aged
- Antibody Formation
- Arthritis, Rheumatoid
(immunology)
- Autoantibodies
(immunology)
- Autoantigens
(immunology)
- Case-Control Studies
- Citrullination
(immunology)
- Extracellular Traps
(immunology)
- Female
- Humans
- Male
- Middle Aged
- Peptides, Cyclic
(immunology)
- Prospective Studies
- Sputum
(immunology)
- Young Adult
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