RGD Reference Report - Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis. - Rat Genome Database

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Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis.

Authors: Van de Stadt, LA  De Koning, MH  Van de Stadt, RJ  Wolbink, G  Dijkmans, BA  Hamann, D  Van Schaardenburg, D 
Citation: van de Stadt LA, etal., Arthritis Rheum. 2011 Nov;63(11):3226-33. doi: 10.1002/art.30537.
RGD ID: 6480508
Pubmed: PMID:21792832   (View Abstract at PubMed)
DOI: DOI:10.1002/art.30537   (Journal Full-text)

OBJECTIVE: To examine how anti-citrullinated protein antibody (ACPA) epitope spreading takes place prior to the onset of clinical rheumatoid arthritis (RA), and to analyze the pattern of autoantigen reactivity at the beginning of the immune response. METHODS: Multiple consecutive serum samples from 79 RA patients who had donated blood before disease onset were available for analysis. Fifty-three patients tested positive for ACPAs prior to the onset of clinical RA. For these patients, a median of 6 (interquartile range 4-9) sequential pre-RA serum samples obtained 1-2 years apart were tested. Reactivity to 5 distinct citrullinated peptides was measured by enzyme-linked immunosorbent assay. Two peptides were derived from fibrinogen, 1 from vimentin, 1 from alpha-enolase, and 1 from filaggrin. RESULTS: In 25 of 53 ACPA-positive patients, seroconversion from ACPA absence to ACPA presence was observed. In 72% of these patients, the immune response started with reactivity to 1 peptide, without preference for a particular peptide. The number of peptides recognized increased over time, without a dominant epitope-spreading pattern. ACPAs appeared in low levels several years prior to the diagnosis of RA. Antibody titers increased markedly approximately 2-4 years before diagnosis. CONCLUSION: Our findings indicate that ACPA epitope spreading occurs over several years prior to the onset of clinical RA. The initial autoimmune response is mostly directed toward only 1 autoantigen, but this is not always the same antigen. The marked increase in ACPA titers a few years prior to the diagnosis of RA suggests a second stage in disease development, which might be due to a variety of factors.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
rheumatoid arthritis  IDA 6480508 RGD 
rheumatoid arthritis  ISOVIM (Homo sapiens)6480508; 6480508 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Vim  (vimentin)

Genes (Mus musculus)
Vim  (vimentin)

Genes (Homo sapiens)
VIM  (vimentin)


Additional Information